Production of new ent-hardwickiic acid derivatives by microbial transformation and their antifungal activity.

Ent-hardwickiic acid is the major compound of Copaifera pubiflora Benth oleoresin traditionally used in Brazilian folk medicine as an antimicrobial agent. Microbial transformation of ent-hardwickiic by Cunninghamella elegans ATCC 10028b resulted in two and five antifungal derivatives (four new ones) produced in the Czapek modified and Koch's K1 media, respectively. The derivatives were isolated and their structures were determined by spectral analysis, namely 1D/2D NMR and HR-ESIMS. All compounds were tested for cytotoxic and antifungal activities and they were not cytotoxic to the tested cell lines, but all derivatives showed fungicidal activity against Candida glabrata and Candida krusei, which have emerged as resistant to fluconazole. One of the yet unreported biotransformation products displayed the strongest activity with minimum fungicidal concentration values smaller than the other compounds, including fluconazole.

Standardized ileal digestible tryptophan and lysine affects the eating and sleeping behavior of 15-30 kg barrows.

The objective of this study was to evaluate the effect of standardized ileal digestible (SID) tryptophan (Trp) and lysine (Lys) levels on eating and sleeping behavior and the respective feed intake of barrows. Sixty-four pigs, averaging 15.00 ± 1.63 kg of initial body weight, were used and distributed in a randomized blocks design, in a 4 × 4 factorial scheme, consisting of four levels of SID Trp (0.155, 0.185, 0.215, 0.245%) and four levels of SID Lys (0.972, 1.112, 1.252, and 1.392%). Behavior evaluation was performed by an instantaneous sampling using 10-min intervals during 24 h, at each 7 days (days 7, 14, and 21), and each day was divided into four times of 6 h each one (08:30-14:20, 14:30-20:20, 20:30-02:20, and 02:30-08:20 h), during all the experimental period, yielding a total of 3 × 24 h behavior recordings (72 h) × 6 10-min intervals, totalizing 432 observations per animal. Data were analyzed by classifying behavior into eating or sleeping. All these behaviors were measured in order to obtain the estimated frequency of the eating and sleeping behaviors. Changes were observed (P<0.05) for all the behavioral parameters during the starting phase. SID Trp and SID Lys showed an interactive positive effect on the estimated frequency of eating behavior, and mainly SID Trp increased the estimated frequency of the sleeping behavior of starting pigs in the nocturnal time. Pig diets with increasing levels of SID Trp and SID Lys until 0.245 and 1.392%, respectively, increased the average daily feed intake, and the interaction of the amino acids increased the estimated frequency of eating behavior during all the starting phase, and mainly the increasing levels of SID Trp increased the estimated frequency of sleeping behavior of pigs from the middle to the end of the starting phase, from 2:30 to 8:20 h.

Optimized Automated Analysis of Live Neuronal Mitochondria Homeostasis Modulation by Isoform-Specific Retinoic Acid Receptors.

The complex mitochondrial network makes it very challenging to segment, follow, and analyze live cells. MATLAB tools allow the analysis of mitochondria in timelapse files, considerably simplifying and speeding up the process of image processing. Nonetheless, existing tools produce a large output volume, requiring individual manual attention, and basic experimental setups have an output of thousands of files, each requiring extensive and time-consuming handling. To address these issues, a routine optimization was developed, in both MATLAB code and live-script forms, allowing for swift file analysis and significantly reducing document reading and data processing. With a speed of 100 files/min, the optimization allows an overall rapid analysis. The optimization achieves the results output by averaging frame-specific data for individual mitochondria throughout time frames, analyzing data in a defined manner, consistent with those output from existing tools. Live confocal imaging was performed using the dye tetramethylrhodamine methyl ester, and the routine optimization was validated by treating neuronal cells with retinoic acid receptor (RAR) agonists, whose effects on neuronal mitochondria are established in the literature. The results were consistent with the literature and allowed further characterization of mitochondrial network behavior in response to isoform-specific RAR modulation. This new methodology allowed rapid and validated characterization of whole-neuron mitochondria network, but it also allows for differentiation between axon and cell body mitochondria, an essential feature to apply in the neuroscience field. Moreover, this protocol can be applied to experiments using fast-acting treatments, allowing the imaging of the same cells before and after treatments, transcending the field of neuroscience.

Effects of exercise training on glucocorticoid-induced muscle atrophy: Literature review.

Glucocorticoids (GCs) administration, such as cortisol acetate (CA) and dexamethasone (DEXA), is used worldwide due to their anti-inflammatory, anti-allergic, and immunosuppressive properties. However, muscle atrophy is one of the primary deleterious induced responses from the chronic treatment with GCs since it stimulates muscle degradation inhibiting muscle protein synthesis. Animal models allow a better understanding of the molecular pathways involved in this process of gene modulation and production of hypertrophic and atrophic proteins. The treatment with GCs, such as DEXA, promotes the reduction of hypertrophic proteins such as serine/threonine tyrosine kinase (AKT), protein kinase mammalian target of rapamycin (mTOR), and ribosomal protein S6 kinase (p70S6K) and increased gene expression or production of atrophic proteins, such as myostatin, muscle atrophic F-box (atrogin-1), or muscle ring finger protein-1 (MuRF-1). In both continuous exercise (CE) and resistance exercise (RE) forms, exercise training is used to mitigate muscle atrophy induced by GCs. The CE attenuated muscle atrophy induced by CA or DEXA in the plantaris and extensor digitorum longus muscles, while RE mitigated the DEXA-induced atrophy in plantaris and flexor hallucis longus muscles. The RE response appears to have occurred by modulation of hypertrophic proteins through increased protein production or phosphorylated/total ratio of mTOR and p70S6K and decreased atrophic protein production of MuRF-1. CE needs future research to understand the molecular pathways of its protective response.

Dexamethasone-Induced Arterial Stiffening Is Attenuated by Training due to a Better Balance Between Aortic Collagen and Elastin Levels.

PURPOSE: Although the cardioprotective benefits of exercise training are well known, the effects of training on dexamethasone (DEX)-induced arterial stiffness are still unclear. This study was aimed at investigating the mechanisms induced by training to prevent DEX-induced arterial stiffness. METHODS: Wistar rats were allocated into 4 groups and submitted to combined training (aerobic and resistance exercises, on alternate days, 60% of maximal capacity, for 74 d) or were kept sedentary: sedentary control rats (SC), DEX-treated sedentary rats (DS), combined training control (CT), and DEX-treated trained rats (DT). During the last 14 d, rats were treated with DEX (50 µg/kg per body weight, per day, s.c.) or saline. RESULTS: DEX increased PWV (+44% vs +5% m/s, for DS vs SC, p<0.001) and increased aortic COL 3 protein level (+75%) in DS. In addition, PWV was correlated with COL3 levels (r=0.682, p<0.0001). Aortic elastin and COL1 protein levels remained unchanged. On the other hand, the trained and treated groups showed lower PWV values (-27% m/s, p<0.001) vs DS and lower values of aortic and femoral COL3 compared with DS. CONCLUSION: As DEX is widely used in several situations, the clinical relevance of this study is that the maintenance of good physical capacity throughout life can be crucial to alleviate some of its side effects, such as arterial stiffness.

Acute toxicity characterization of organic UV-filters and chronic exposure revealing multigenerational effects in DAPHNIA MAGNA.

Organic ultraviolet (UV) filters have often been detected in aquatic ecosystems in concentrations ranging from ng/L to µg/L. However, both their acute and chronic effects on aquatic organisms have been insufficiently explored. This study aimed to evaluate acute toxicity of some of the main UV filters used worldwide (2-ethylhexyl,4-methoxycinnamate/EHMC, avobenzone/AVO, benzophenone-3/BP-3, and octocrylene/OC), in three aquatic organisms (Artemia salina, Desmodesmus subspicatus, and Daphnia magna), and to further investigate multigenerational effects in D. magna. After acute toxicity was confirmed, daphnids were chronically exposed to environmentally relevant concentrations of UV filters for two consecutive generations (F0 and F1), and reproductive endpoints, as well as catalase (CAT) and glutathione-S-transferase (GST) activities, were assessed. EHMC showed the most toxic potential, with the lowest EC50 values for the three organisms. On the other hand, reproductive delays and a decrease in the reproduction rate were observed in the F1 generation exposed to AVO (4.4 µg/L), BP-3 (0.17 µg/L), EHMC (0.2 µg/L), and MIX. An increase of the CAT activity in organisms exposed to BP-3 and EHMC suggested induction of the antioxidant system. Although no reproductive effect was observed in the first generation, toxic effects obtained in the F1 revealed the importance of multigenerational studies and the potential harm of UV filters to the life cycle of D. magna, even at environmentally relevant concentrations. This emphasizes the need for further studies considering these levels of exposure and more realistic experimental designs to better understand their potential risks. Environmentally relevant concentrations of Organic UV filters are not lethal to aquatic organisms, however may affect reproductive parameters in Daphnia magna though multigenerational exposures.

Treatment of a clinical analysis laboratory wastewater from a hospital by photo-Fenton process at four radiation settings and toxicity response.

The photo-Fenton process was performed with four radiation settings to treat clinical analysis laboratory wastewater (CALWW) from a hospital, with the aim of evaluating its treatability and acute toxicity response in Daphnia magna and Lactuca sativa. The experiments were performed in a borosilicate bench-scale conventional reactor for 320 min. The light radiation was suspended 13 cm from the CALWW surface for mild radiation or immersed into the matrix for intense radiation. All photo-Fenton experimental conditions were set at pH 3.0, 15 mg L-1 of Fe2+, and initial H2O2 of 300 mg L-1. The initial Fe2+ concentration was converted to Fe3+ ion in the first 15 min of photooxidation for all processes. Furthermore, the intense radiation processes regenerated Fe2+ faster than other systems. Neither mild UVA-Vis nor mild UVC-Vis radiation significantly treated the organic matter or phenols. However, mild UVC-Vis resulted in a higher biodegradability transformation rate (biochemical oxygen demand/chemical oxygen demand 0.51), indicating that it could treat more recalcitrant organic matter than mild UVA-Vis. Intense radiation proved to be more efficient, with a chemical oxygen demand removal rate of 95% for intense UVA-Vis and 99% for intense UVC-Vis treatments. All treatments reduced acute toxicity in D. magna. Moreover, photo-Fenton treatment by intense UVA-Vis decreased toxicity ~98%, compared to mild and intense UVC-Vis, ~75%. Both of the mild radiation treatments inhibited the germination of L. sativa seeds. The intense UVA-Vis photo-Fenton treatment was the only setting that removed phytotoxicity, resulting in a non-significant effect, and the intense UVC-Vis treatment inhibited the seed growth.

Sublethal effects of triclosan and triclocarban at environmental concentrations in silver catfish (Rhamdia quelen) embryos.

Although banished in some countries, triclosan (TCS) and triclocarban (TCC) have been detected in surface waters in concentrations ranging from ng L-1 to µg L-1 and have shown to affect non-target organisms posing risk to aquatic ecosystems. However, the majority of the studies consider higher levels of these chemicals and single exposure effects to investigate their potential risks, rather than using environmentally relevant concentrations and their binary mixture. In this study, the toxicity of TCS and TCC, and their binary mixture was assessed in catfish embryos (Rhamdia quelen, a south American native species) exposed to environmental concentrations during 96 h. Organisms were evaluated through the endpoints of developmental abnormalities (spine, fin, facial/cranial and thorax), biochemical biomarkers related to oxidative stress responses: catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST) activities, protein carbonylation (PCO) and neurotoxicity by acetylcholinesterase activity (AChE). The data showed that TCS caused fin abnormalities, decrease of SOD activity and increase of AChE activity in the catfish embryos of 96hpf. On the other hand, TCC and the binary mixture showed a higher abnormality index for the 96hpf embryos, and an induction of CAT and GST activities for the mixture treatment. The results obtained were able to show potential, but not severe, toxicity of TCS and TCC even in low concentrations and a short period of exposure. The relevance of studies approaching real scenarios of exposure should be reinforced, considering environmental concentrations of chemicals, interactions of contaminants in complex mixtures and the use of a native species such as R. quelen exposed during initial stages of development.

The solar photo-Fenton process at neutral pH applied to microcystin-LR degradation: Fe2+, H2O2 and reaction matrix effects.

Microcystins are a group of cyanotoxins with known hepatotoxic effects, and their presence in drinking water represents a public health concern all over the world. The main objective of this work was to evaluate the solar photo-Fenton process at near-neutral pH in the degradation of microcystin-LR (MC-LR) under conditions close to those found in bloom episodes, with a high concentration of cell debris and natural organic matter (NOM). The influence of experimental parameters such as Fe2+ and H2O2 concentrations, reaction matrix, and the presence of scavenger ions, as well as ecotoxicity before and after treatment, was also evaluated. The reaction matrix was obtained from Microcystis aeruginosa cultivated in ASM-1 medium (ACE1 and ACE2 extracts). H2O2 and Fe2+ concentrations were optimized by 22 factorial design with the central point in a bench-scale solar reactor, using ACE1 extract, and the improved condition was applied in a compound parabolic collector (CPC) reactor, for the ACE2, natural water (RVW) and natural water with M. aeruginosa crude extract (RVCE). Matrix effect assays indicated that radical scavengers present in the medium were responsible for the decrease in the mineralization rates. The solar photo-Fenton process in the CPC reactor achieved COD (75%) and MC-LR (70%) reduction after 120 min at pH = 7.8, [H2O2]/COD = 3.18 and [H2O2]/[Fe2+] = 10 for the ACE2 sample. When the same conditions were applied to the RVCE sample, the process removed 77% of DOC and up to 99% of MC-LR after 45 min of the reaction. Sinapis alba bioassays showed that there was no increase in ecotoxicity after the solar photo-Fenton treatment. These results demonstrate the potential of the solar photo-Fenton process at neutral pH as an additional step in the treatment of natural matrices contaminated with microcystins. In addition, the work reinforces the importance of bioassays in treatment process monitoring.

Solitonic lattice and Yukawa forces in the rare-earth orthoferrite TbFeO3.

The random fluctuations of spins give rise to many interesting physical phenomena, such as the 'order-from-disorder' arising in frustrated magnets and unconventional Cooper pairing in magnetic superconductors. Here we show that the exchange of spin waves between extended topological defects, such as domain walls, can result in novel magnetic states. We report the discovery of an unusual incommensurate phase in the orthoferrite TbFeO(3) using neutron diffraction under an applied magnetic field. The magnetic modulation has a very long period of 340 Å at 3 K and exhibits an anomalously large number of higher-order harmonics. These domain walls are formed by Ising-like Tb spins. They interact by exchanging magnons propagating through the Fe magnetic sublattice. The resulting force between the domain walls has a rather long range that determines the period of the incommensurate state and is analogous to the pion-mediated Yukawa interaction between protons and neutrons in nuclei.