Effects of Rosmarinus officinalis L. (Laminaceae) essential oil on adult and larvae of Drosophila melanogaster.

Rosmarinus officinalis (Lamiaceae family), also known as "alecrim," is a perennial herb, typical of the Mediterranean region and widely distributed in Brazilian territory. Despite having demonstrated several properties of human interest, insecticide/larvicidal effect of essential oil from R. officinalis on insects remains unclear. In this study, we tested the effects of R. officinalis essential oil on biomarkers of oxidative damage in Drosophila melanogaster. Exposure to R. officinalis essential oil increased adult mortality and decreased geotaxis behavior in adult fruit flies. In addition, essential oil increased of larval mortality and impaired the developmental success in D. melanogaster. R. officinalis essential oil showed a significant repellent effect, with duration time of about 6 h. To understand the mechanism underlying the toxicity of essential oil both pro-oxidant effects and biomarkers of oxidative damage were evaluated in exposed flies. Exposure to essential oil caused a significant redox imbalance with impairment of both enzymatic and non-enzymatic antioxidant system and increased the lipid peroxidation levels. These results suggest that R. officinalis essential oil can be used as a bioinsecticide and/or larvicide as well as an alternative insect repellent.

Strategies to Assess the Impact of Sustainable Functional Food Ingredients on Gut Microbiota.

Nowadays, it is evident that food ingredients have different roles and distinct health benefits to the consumer. Over the past years, the interest in functional foods, especially those targeting gut health, has grown significantly. The use of industrial byproducts as a source of new functional and sustainable ingredients as a response to such demands has raised interest. However, the properties of these ingredients can be affected once incorporated into different food matrices. Therefore, when searching for the least costly and most suitable, beneficial, and sustainable formulations, it is necessary to understand how such ingredients perform when supplemented in different food matrices and how they impact the host's health. As proposed in this manuscript, the ingredients' properties can be first evaluated using in vitro gastrointestinal tract (GIT) simulation models prior to validation through human clinical trials. In vitro models are powerful tools that mimic the physicochemical and physiological conditions of the GIT, enabling prediction of the potentials of functional ingredients per se and when incorporated into a food matrix. Understanding how newly developed ingredients from undervalued agro-industrial sources behave as supplements supports the development of new and more sustainable functional foods while scientifically backing up health-benefits claims.

Skincare potential of a sustainable postbiotic extract produced through sugarcane straw fermentation by Saccharomyces cerevisiae.

Postbiotics are defined as a "preparation of inanimate microorganisms and/or their components that confers a health benefit on the host." They can be produced by fermentation, using culture media with glucose (carbon source), and lactic acid bacteria of the genus Lactobacillus, and/or yeast, mainly Saccharomyces cerevisiae as fermentative microorganisms. Postbiotics comprise different metabolites, and have important biological properties (antioxidant, anti-inflammatory, etc.), thus their cosmetic application should be considered. During this work, the postbiotics production was carried out by fermentation with sugarcane straw, as a source of carbon and phenolic compounds, and as a sustainable process to obtain bioactive extracts. For the production of postbiotics, a saccharification process was carried out with cellulase at 55°C for 24 h. Fermentation was performed sequentially after saccharification at 30°C, for 72 h, using S. cerevisiae. The cells-free extract was characterized regarding its composition, antioxidant activity, and skincare potential. Its use was safe at concentrations below ~20 mg mL-1 (extract's dry weight in deionized water) for keratinocytes and ~ 7.5 mg mL-1 for fibroblasts. It showed antioxidant activity, with ABTS IC50 of 1.88 mg mL-1 , and inhibited elastase and tyrosinase activities by 83.4% and 42.4%, respectively, at the maximum concentration tested (20 mg mL-1 ). In addition, it promoted the production of cytokeratin 14, and demonstrated anti-inflammatory activity at a concentration of 10 mg mL-1 . In the skin microbiota of human volunteers, the extract inhibited Cutibacterium acnes and the Malassezia genus. Shortly, postbiotics were successfully produced using sugarcane straw, and showed bioactive properties that potentiate their use in cosmetic/skincare products.

Permissible concentration of mancozeb in Brazilian drinking water elicits oxidative stress and bioenergetic impairments in embryonic zebrafish.

Mancozeb (MZ) is widely used as a fungicide in Brazil due to its effectiveness in combating fungal infections in plantations. However, its toxicity to non-target organisms, including aquatic organisms, has been reported in the literature. Recently, Brazilian legislation was updated to allow a concentration of 8 µg/L of MZ in drinking water (Ordinance GM/MS nº 888, of May 4, 2021). However, the safety of this concentration for aquatic organisms has not yet been put to the test. To address this gap, we conducted a study using zebrafish (Danio rerio) embryos at 4 hpf exposed to MZ at the concentration allowed by law, as well as slightly higher sublethal concentrations (24, 72, and 180 µg/L), alongside a control group. We evaluated various morphophysiological markers of toxicity, including survival, spontaneous movements, heart rate, hatching rate, body axis distortion, total body length, total yolk sac area, and total eye area. Additionally, we measured biochemical biomarkers such as reactive oxygen species (ROS) levels, lipid peroxidation, non-protein thiols (NPSH), and mitochondrial bioenergetic parameters. Our results showed that the concentration of 8 µg/L, currently permitted in drinking water according to Brazilian legislation, increased ROS production levels and caused alterations in mitochondrial physiology. Among the markers assessed, mitochondrial bioenergetic function appeared to be the most sensitive indicator of MZ embryotoxicity, as a decrease in complex I activity was observed at concentrations of 8 and 180 µg/L. Furthermore, concentrations higher than 8 µg/L impaired morphophysiological markers. Based on these findings, we can infer that the concentration of MZ allowed in drinking water by Brazilian environmental legislation is not safe for aquatic organisms. Our study provides evidence that this fungicide is a potent embryotoxic agent, highlighting the potential risks associated with its exposure.

Sugarcane Straw as a Source of Arabinoxylans: Optimization and Economic Viability of a Two-Step Alkaline Extraction.

Sugarcane processing produces a significant amount of byproducts in the form of straw and bagasse, which are rich in cellulose, hemicellulose, and lignin. This work aims to provide a valorization approach to sugarcane straw by optimizing a two-step alkaline extraction of arabinoxylans by a response surface methodology to evaluate a potential industrial-scale production. Sugarcane straws were delignified using an alkaline-sulfite pretreatment, followed by alkaline extraction and precipitation of arabinoxylan, a two-step process optimized using a response surface methodology. A KOH concentration of (2.93-17.1%) and temperature (18.8-61.2 °C) were chosen as independent variables, and the arabinoxylan yield (%) as a response variable. The model application shows that KOH concentration, temperature, and the interaction between both independent variables are significant in extracting arabinoxylans from straw. The best-performing condition was further characterized by FTIR, DSC, and chemical and molecular weight evaluation. The straws arabinoxylans presented high purities levels, ca. 69.93%, and an average molecular weight of 231 kDa. The overall estimated production cost of arabinoxylan from straw was 0.239 €/g arabinoxylan. This work demonstrates a two-step alkaline extraction of the arabinoxylans method, as well as their chemical characterization and economic viability analysis, that can be used as a model for industrial scale-up production.

Lignin from sugarcane bagasse as a prebiotic additive for poultry feed.

Diet is a crucial factor on health and well-being of livestock animals. Nutritional strengthening with diet formulations is essential to the livestock industry and animal perfor-mance. Searching for valuable feed additives among by-products may promote not only circular economy, but also functional diets. Lignin from sugarcane bagasse was proposed as a potential prebiotic additive for chickens and incorporated at 1 % (w/w) in commercial chicken feed, tested in two feed forms, namely, mash and pellets. Physico-chemical characterization of both feed types with and without lignin was performed. Also, the prebiotic potential for feeds with lignin was assessed by an in vitro gastrointestinal model and evaluated the impact on chicken cecal Lactobacillus and Bifidobacterium. As for the pellet's physical quality, there was a higher cohesion of the pellets with lignin, indicating a higher resistance to breakout and lignin decreases the tendency of the pellets for microbial contamination. Regarding the prebiotic potential, mash feed with lignin showed higher promotion of Bifidobacterium in comparison with mash feed without lignin and to pellet feed with lignin. Lignin from sugarcane bagasse has prebiotic potential as additive to chicken feed when supplemented in mash feed diets, presenting itself as a sustainable and eco-friendly alternative to chicken feed additives supplementation.

Mancozeb impairs mitochondrial and bioenergetic activity in Drosophila melanogaster.

Mancozeb (MZ) is a broad-spectrum fungicide used worldwide in several crops. Neurological disorders in humans and animals have been associated with exposure to this compound by mechanisms still not fully understood. Drosophila melanogaster represents a reliable model in toxicological studies, presenting genetic and biochemical similarities with mammals. In this study, D. melanogaster flies were exposed for 15 days to MZ through the food (5 and 10 mg/mL). After that period, the efficiency of mitochondrial respiration complexes and metabolic markers were analyzed and evaluated. Flies presented weight loss, lower glucose, trehalose, and glycogen levels, and augmented levels of triglycerides concerning control (non-treated group). Acetyl-CoA Synthetase (ACeCS-1) and Acyl-Coenzyme Synthetase (ACSL1) contents were unchanged by MZ treatment. Mitochondrial respiration of flies was targeted by MZ treatment, evidenced by a decrease in oxygen consumption and bioenergetics rate and inhibition in mitochondrial complexes I/II. These results suppose that an impairment in mitochondrial respiration jointly with reduced levels of energetic substrates might be a mechanism involved in MZ deleterious effects, possibly by the limitation of ATP's availability, necessary for essential cellular processes.

Fecal microbiota transplantation in the intestinal decolonization of carbapenamase-producing enterobacteriaceae

BACKGROUND AND AIMS: fecal microbiota transplantation (FMT) is effective for recurrent Clostridium difficile infection (CDI). Intestinal decolonization of carbapenamase-producing enterobacteriaceae (CPE) can prevent transmission and infection by these agents. The aim of this study was to assess CPE decolonization after FMT. METHODS: this was a case-series study that consecutively included all CPE-carriers that underwent FMT between 2014 and 2019. The indications included refractory/recurrent CDI and CPE-decolonization. RESULTS: out of 21 CPE-carriers, eight were excluded due to incomplete post-FMT testing. CPE decolonization was confirmed in 76.9 % (n = 10). The median decolonization time was 16-weeks (IQR-23) and ranged from two to 53 weeks. CONCLUSION: FMT may be used in the clinical practice for CPE-decolonization as an alternative to combined antibiotic regimens

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Effects of caffeine on brain antioxidant status and mitochondrial respiration in acetaminophen-intoxicated mice.

Hepatic encephalopathy is a pathophysiological complication of acute liver failure, which may be triggered by hepatotoxic drugs such as acetaminophen (APAP). Although APAP is safe in therapeutic concentration, APAP overdose may induce neurotoxicity, which is mainly associated with oxidative stress. Caffeine is a compound widely found in numerous natural beverages. However, the neuroprotective effect of caffeine remains unclear during APAP intoxication. The present study aimed to investigate the possible modulatory effects of caffeine on brain after APAP intoxication. Mice received intraperitoneal injections of APAP (250 mg/kg) and/or caffeine (20 mg/kg) and, 4 h after APAP administration, samples of brain and blood were collected for the biochemical analysis. APAP enhanced the transaminase activity levels in plasma, increased oxidative stress biomarkers (lipid peroxidation and reactive oxygen species), promoted an imbalance in endogenous antioxidant system in brain homogenate and increased the mortality. In contrast, APAP did not induce dysfunction of the mitochondrial bioenergetics. Co-treatment with caffeine modulated the biomarkers of oxidative stress as well as antioxidant system in brain. Besides, survival assays demonstrated that caffeine protective effects could be dose- and time-dependent. In addition, caffeine promoted an increase of mitochondrial bioenergetics response in brain by the enhancement of the oxidative phosphorylation, which could promote a better energy supply necessary for brain recovery. In conclusion, caffeine prevented APAP-induced biochemical alterations in brain and reduced lethality in APAP-intoxicated mice, these effects may relate to the preservation of the cellular antioxidant status, and these therapeutic properties could be useful in the treatment of hepatic encephalopathy induced by APAP intoxication.

Fecal microbiota transplantation in the intestinal decolonization of carbapenamase-producing enterobacteriaceae.

BACKGROUND AND AIMS: fecal microbiota transplantation (FMT) is effective for recurrent Clostridium difficile infection (CDI). Intestinal decolonization of carbapenamase-producing enterobacteriaceae (CPE) can prevent transmission and infection by these agents. The aim of this study was to assess CPE decolonization after FMT. METHODS: this was a case-series study that consecutively included all CPE-carriers that underwent FMT between 2014 and 2019. The indications included refractory/recurrent CDI and CPE-decolonization. RESULTS: out of 21 CPE-carriers, eight were excluded due to incomplete post-FMT testing. CPE decolonization was confirmed in 76.9 % (n = 10). The median decolonization time was 16-weeks (IQR-23) and ranged from two to 53 weeks. CONCLUSION: FMT may be used in the clinical practice for CPE-decolonization as an alternative to combined antibiotic regimens.

Guanosine protects against behavioural and mitochondrial bioenergetic alterations after mild traumatic brain injury.

Traumatic brain injury (TBI) constitutes a heterogeneous cerebral insult induced by traumatic biomechanical forces. Mitochondria play a critical role in brain bioenergetics, and TBI induces several consequences related with oxidative stress and excitotoxicity clearly demonstrated in different experimental model involving TBI. Mitochondrial bioenergetics alterations can present several targets for therapeutics which could help reduce secondary brain lesions such as neuropsychiatric problems, including memory loss and motor impairment. Guanosine (GUO), an endogenous neuroprotective nucleoside, affords the long-term benefits of controlling brain neurodegeneration, mainly due to its capacity to activate the antioxidant defense system and maintenance of the redox system. However, little is known about the exact protective mechanism exerted by GUO on mitochondrial bioenergetics disruption induced by TBI. Thus, the aim of this study was to investigate the effects of GUO in brain cortical and hippocampal mitochondrial bioenergetics in the mild TBI model. Additionally, we aimed to assess whether mitochondrial damage induced by TBI may be related to behavioral alterations in rats. Our findings showed that 24 h post-TBI, GUO treatment promotes an adaptive response of mitochondrial respiratory chain increasing oxygen flux which it was able to protect against the uncoupling of oxidative phosphorylation (OXPHOS) induced by TBI, restored the respiratory electron transfer system (ETS) established with an uncoupler. Guanosine treatment also increased respiratory control ratio (RCR), an indicator of the state of mitochondrial coupling, which is related to the mitochondrial functionality. In addition, mitochondrial bioenergetics failure was closely related with locomotor, exploratory and memory impairments. The present study suggests GUO treatment post mild TBI could increase GDP endogenous levels and consequently increasing ATP levels promotes an increase of RCR increasing OXPHOS and in substantial improve mitochondrial respiration in different brain regions, which, in turn, could promote an improvement in behavioral parameters associated to the mild TBI. These findings may contribute to the development of future therapies with a target on failure energetic metabolism induced by TBI.

Therapeutic Cannabis and COVID-19: between opportunism and infoxication. / Cannabis terapéutico y COVID-19: entre el oportunismo y la infoxicación.

Editorial.

Editorial.

Caffeine effects on systemic metabolism, oxidative-inflammatory pathways, and exercise performance.

Caffeine, a xanthine alkaloid compound, is consumed widely and daily by humans, as it is present in several regular beverages such as tea, coffee, soda beverages, and some drugs. Its consumption triggers arousal and alertness, improves mood, and causes the release of catecholamines, which induce beneficial effects on human behavior. Nonetheless, caffeine has been related to other beneficial effects such as antioxidant and anti-inflammatory actions that are extremely important to human health, altering the cellular redox and inflammatory status in a dose-dependent manner. Caffeine intake has also shown ergogenic effects, which are attributed to different factors, such as enhanced substrate utilization, fatigue delay, and alertness. As such, caffeine has been consumed by athletes from different sports modalities, with positive and negative effects declared. Although peripheral tissues such as the heart, skeletal muscle, and adipocytes are also impacted, there is a deficit of recognized mechanisms in systemic metabolism when compared to caffeine action in the central nervous system. This review summarizes the most relevant classical and current literature available regarding the use of caffeine in different metabolic situations, such as oxidative and inflammatory status, as well as anaerobic and aerobic physical exercises. Here, we identified the non-central nervous system caffeine mechanisms modulation, as most are still unknown or controversial, highlighting its influence in the peripheral system and its essential and crucial impacts on the human's organism adaptation.

Acetaminophen Oxidation and Inflammatory Markers - A Review of Hepatic Molecular Mechanisms and Preclinical Studies.

Acetaminophen is a widely used analgesic for pain management, especially useful in chronic diseases, such as rheumatoid arthritis. However, easy access to this medicine has increased the occurrence of episodes of poisoning. Patients often develop severe liver damage, which may quickly lead to death. Consequently, numerous studies have been conducted to identify new biomarkers that allow the prediction of the degree of acetaminophen intoxication and thus intervene in a timely manner to save patients' lives. This review highlights the main mechanisms of the induction and progression of liver damage arising from acetaminophen poisoning. In addition, we have discussed the possibility of using new clinical biomarkers for detecting acetaminophen poisoning.

The insertion of functional groups in organic selenium compounds promote changes in mitochondrial parameters and raise the antibacterial activity.

Organic selenium compounds are widely associated with numerous pharmacological properties. However, selenium compounds, such as Ebselen (Ebs) and Diphenyl Diselenide (DPDS), could interact with mitochondrial respiratory complexes, especially with thiol groups. The present study evaluated whether the insertion of functional groups, o-methoxy, and p-methyl on organic selenium compounds promotes changes in mitochondrial functioning parameters and whether this is related to antibacterial activity. Here we tested some in vitro parameters after the exposure of mitochondria to different concentrations of ß-selenoamines 1-phenyl-3-(p-tolylselanyl)propan-2-amine (C1) and 1-(2-methoxyphenylselanyl)-3-phenylpropan-2-amine (C2) and analogs of DPDS 1,2-bis(2-methoxyphenyl)diselenide (C3) and 1,2-bisp-tolyldiselenide (C4). We also evaluated the antibacterial activity of ß-selenoamines and diselenides against Methicillin-resistant Staphylococcus aureus and Escherichia coli. Our results showed that o-methoxy insertion increased the antioxidant properties, without affecting the mitochondrial membrane potential. The compounds with a p-methyl insertion affected the mitochondrial membrane potential and significantly decreased the State III respiration and RCR. Besides, the p-methyl compounds presented antibacterial activity at lower concentrations than those shown in o-methoxy, precisely by the same mechanism that promotes damage to thiol groups and better absorption in gram-positive bacteria due to their relationship with cell wall constituents. Finally, our study confirms that structural modifications in organic selenium compounds provide changes in mitochondrial functioning but also raise their antibacterial effect. This strategy can be used as a target for the development of new enough potent antibacterial to restrict the advance of resistant bacterial infections.

The potential of insects as food sources - a review.

Entomophagy is a long-time practice and a food source for many cultures. Still, many societies have abandoned it a long time ago, and regard it as a primal behavior. However, nowadays, the challenge for food demand, with the urge of new nutritional sources, and the problems of undernourishment, mainly on underdeveloped countries, has reached a point where a new perspective is demanded. This review gathers some of the most recent studies regarding the potential benefits and concerns of entomophagy, trying to show the potential of insects as food source and possible ways to introduce them in cultures that have disregarded entomophagy. Entomophagy is taking its place, showing the grand potential of insects as feed and food source. As neophobia and disgust are the main western cultures barriers to accept entomophagy, today's comprehension of this practice and processing capabilities can take that source, to any dish in any form. A simple but nutritive insect powder can create a path to a widely, sustainable, rich food source-insects.

Cannabis terapéutico y COVID-19: entre el oportunismo y la infoxicación / Therapeutic Cannabis and COVID-19: between opportunism and infoxication

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Acute Exposure to Permethrin Modulates Behavioral Functions, Redox, and Bioenergetics Parameters and Induces DNA Damage and Cell Death in Larval Zebrafish.

Permethrin (PM) is a synthetic pyrethroid insecticide widely used as domestic repellent. Damage effects to nontarget organisms have been reported, particularly in the early stages of development. Studies indicate redox unbalance as secondary PM effect. Therefore, our goal was to investigate the acute PM effects on larval zebrafish. Larvae (6 days postfertilization) were exposed to PM (25-600 µg/L) during 24 hours, and 50% lethal concentration was estimated. For subsequent assays, the sublethal PM concentrations of 25 and 50 µg/L were used. PM increased anxiety-like behaviors according to the Novel Tank and Light-Dark tests. At the molecular level, PM induced increased ROS, which may be related to the increased lipid peroxidation, DNA damage, and apoptosis detected in PM-exposed organisms. In parallel, upregulation of the antioxidant system was detected after PM exposure, with increased superoxide dismutase, glutathione S-transferase and glutathione reductase activities, and thiol levels. The increased of Nrf2 target genes and the activation of an electrophile response element-driven reporter Tg(EPRE:LUC-EGFP) suggest that the Nrf2 pathway can mediate a fast response to PM, leading to antioxidant amplification. By using high-resolution respirometry, we found that exposure to PM decreased the oxygen consumption in all respiratory stages, disrupting the oxidative phosphorylation and inhibiting the electron transfer system, leading to decrease in bioenergetics capacity. In addition, PM led to increases of residual oxygen consumption and changes in substrate control ratio. Glucose metabolism seems to be affected by PM, with increased lactate dehydrogenase and decreased citrate synthase activities. Taken together, our results demonstrated the adverse effects of acute sublethal PM concentrations during larval development in zebrafish, causing apparent mitochondrial dysfunction, indicating a potential mechanism to redox unbalance and oxidative stress, which may be linked to the detected cell death and alterations in normal behavior patterns caused by acute PM exposure.

Potential prebiotic activity of Tenebrio molitor insect flour using an optimized in vitro gut microbiota model.

The Tenebrio molitor insect flour (TMIF) is considered a nutritive food ingredient, but its impact at the gut microbiota level and its potential prebiotic activity still need be assessed. For such studies, an in vitro simulation model of gut microbiota was optimized. Pure cultures of Lactobacillus and Bifidobacterium strains in monocultures and co-cultures (pairs and consortium) were used in this model to evaluate the effect of TMIF on the viability and metabolic activity of those bacteria. The optimization of the in vitro model of the gut microbiota was successful, and growth of the most important groups of bacteria in the gut microbiota was observed. So this model can be used to study the effects of other ingredients at that level. It also enabled pinpointing the prebiotic effects of the studied TMIF suggesting possible symbiotic interactions. In addition, the direct effect of the TMIF on bacterial cells, when in nutritive stress was also evaluated. In terms of TMIF effects on probiotic bacteria viability and growth, no negative effects were observed, and even an enhancement of growth and an increase of production of short chain fatty acids (SCFA) and lactate, in most of the cases, was observed. Also, this study showed that TMIF helps in maintaining the viability of bacteria during incubation time when these are under nutritional stress conditions. A potential prebiotic effect of TMIF is then predictable with this study, opening a path to new research on this subject.

Guanosine protects against Ca2+-induced mitochondrial dysfunction in rats.

Mitochondria play an important role in cell life and in the regulation of cell death. In addition, mitochondrial dysfunction contributes to a wide range of neuropathologies. The nucleoside Guanosine (GUO) is an endogenous molecule, presenting antioxidant properties, possibly due to its direct scavenging ability and/or from its capacity to activate the antioxidant defense system. GUO demonstrate a neuroprotective effect due to the modulation of the glutamatergic system and maintenance of the redox system. Thus, considering the few studies focused on the direct effects of GUO on mitochondrial bioenergetics, we designed a study to evaluate the in vitro effects of GUO on rat mitochondrial function, as well as against Ca2+-induced impairment. Our results indicate that GUO prevented mitochondrial dysfunction induced by Ca2+ misbalance, once GUO was able to reduce mitochondrial swelling in the presence of Ca2+, as well as ROS production and hydrogen peroxide levels, and to increase manganese superoxide dismutase activity, oxidative phosphorylation and tricarboxylic acid cycle activities. Our study indicates for the first time that GUO could direct prevent the mitochondrial damage induced by Ca2+ and that these effects were not related to its scavenging properties. Our data indicates that GUO could be included as a new pharmacological strategy for diseases linked to mitochondrial dysfunction.