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Abstract Lipopolysaccharide (LPS) challenge in mice has been used to identify the mechanisms and therapeutics for neuroinflammation. In this study, we aimed to comprehensively evaluate the behavioral changes including locomotion, exploration, and memory, correlating them with a panel of thirteen inflammatory cytokines in both blood and brain. We found that acute LPS administration (0.83 mg/Kg i.p.) reduced body weight, food intake, and glucose levels compared to the saline-injected mice, concomitant with decreased activity in home cage monitoring. Locomotion was significantly reduced in Open Field, Introduced Object, and Y-Maze tests. Decreased exploratory behavior in the Y-Maze and Introduced Object tests was noticed, by measuring the number of arms explored and object interaction time, respectively. Additionally, in rotarod, LPS administration led to a significant decrease in the distance achieved, while in the MouseWalker, LPS led to a reduction in average velocity. LPS induced a decrease in microglia ramification index in the motor cortex and the striatum, while surprisingly a reduction in microglia number was observed in the motor cortex. The concentrations of thirteen cytokines in the blood were significantly altered, while only CXCL1, CCL22, CCL17, G-CSF, and IL-12p40 were changed in the brain. Correlations between cytokine levels in blood and brain were found, most notably for CCL17 and CCL22. TGFβ was the only one with negative correlations to other cytokines. Correlations between cytokines and behavior changes were also disclosed, especially for CCL17, CCL22, G-CSF, and IL-6 and negatively for TGFβ and IL-10. In summary, our study employing acute LPS challenge in mice has revealed a comprehensive profile of behavioral alterations alongside significant changes in inflammatory cytokine levels, both in peripheral blood and brain tissue. These findings contribute to a deeper understanding of the interplay between inflammation and behavior, with possible implications for identifying prognostics and therapeutic targets for neuroinflammatory conditions.

Abstract Staphylococcus aureus is considered a high priority pathogen by the World Health Organization due to its high prevalence and the potential to form biofilms. Currently, the available treatments for S. aureus biofilm-associated infections do not target the extracellular polymeric substances (EPS) matrix. This matrix is a physical barrier to bactericidal agents, contributing to the increase of antimicrobial tolerance. The present work proposes the development of lipid nanoparticles encapsulating caspofungin (CAS) as a matrix-disruptive nanosystem. The nanoparticles were functionalized with D-amino acids to target the matrix. In a multi-target nano-strategy against S. aureus biofilms, CAS-loaded nanoparticles were combined with a moxifloxacin-loaded nanosystem, as an adjuvant to promote the EPS matrix disruption. In vitro and in vivo studies showed biofilm reduction after combining the two nanosystems. Besides, the combinatory therapy showed no signs of bacterial dissemination into vital organs of mice, while dissemination was observed for the treatment with the free compounds. Additionally, the in vivo biodistribution of the two nanosystems revealed their potential to reach and accumulate in the biofilm region, after intraperitoneal administration. Thus, this nano-strategy based on the encapsulation of matrix-disruptive and antibacterial agents is a promising approach to fight S. aureus biofilms.

Damaged yacon roots, often discarded, are a rich source of sweet carbohydrates. In this context, yacon roots from the Hualqui and Crespo varieties were characterized and processed into low-calorie and low-glycemic syrups for sugar reduction in foods. Syrups were obtained using, as technological adjuvants, lemon juice and its most relevant components: citric acid and ascorbic acid. The Hualqui variety was found to be mostly composed of fructose (210 g/kg), while the Crespo variety was rich in inulin (352 g/kg). The use of lemon juice during syrup production promoted the hydrolysis of inulin to fructooligosaccharides and fructose, yielding syrups with competitive relative sweetness (0.52–0.91), glycemic index (0.21–0.40), and caloric values (186–263 kcal/100 g) to commercial syrups. The increase in citric acid concentrations promoted inulin hydrolysis, yielding, at the highest concentration, syrups with higher fructose (333–445 g/kg) and kesto-type fructooligosaccharides (11–85 g/kg) content and lower surface stickiness and stringiness. The addition of ascorbic acid, as an antioxidant agent, decreased by 10% the free sugar content, negatively impacting the sweetness level. These results evidence that fructooligosaccharides-rich syrup can be obtained from yacon-damaged roots with tailored sweetness and low glycemic and caloric properties.

The Aryl Hydrocarbon Receptor (AHR) is a ligand-dependent transcription factor able to control complex transcriptional processes in several cell types, which has been correlated with various diseases, including inflammatory bowel diseases (IBD). Numerous studies have described different compounds as ligands of this receptor, like xenobiotics, natural compounds, and several host-derived metabolites.Dietary (poly)phenols have been studied regarding their pleiotropic activities (e.g., neuroprotective and anti-inflammatory), but their AHR modulatory capabilities have also been considered. However, dietary (poly)phenols are submitted to extensive metabolism in the gut (e.g., gut microbiota). Thus, the resulting gut phenolic metabolites could be key players modulating AHR since they are the ones that reach the cells and may exert effects on the AHR throughout the gut and other organs. This review aims at a comprehensive search for the most abundant gut phenolic metabolites detected and quantified in humans to understand how many have been described as AHR modulators and what could be their impact on inflammatory gut processes. Even though several phenolic compounds have been studied regarding their anti-inflammatory capacities, only 1 gut phenolic metabolite, described as AHR modulator, has been evaluated on intestinal inflammatory models. Searching for AHR ligands could be a novel strategy against IBD.

Purpose The colon and ileum play significant roles on liver physiology. Studies about simultaneous hepatectomy and colectomy or enterectomy are scarce and controversial. We investigated and compared the effects of ileum and colon resection on liver regeneration. Materials and Methods Twenty four Wistar rats were allocated in group I-(sham), group II-70% hepatectomy; group III-70% hepatectomy + ileal resection, and group IV-70% hepatectomy + partial colectomy. On the sixth day, serum hepatic enzymes, albumin, hepatocyte growth-factor (HGF) and transforming growth factor-alpha (TGF-α) were measured. The hepatic regeneration rate was estimated. Ki-67 immunohistochemical analysis was done in remnant liver. Results Hepatic enzymes levels were significantly higher in group III rats comparing to the other groups (p 0.05). Cytokines HGF and TGF-α levels in group IV were significantly higher than in the other groups (p 0.05). Conclusion Ileum and colon resection have different effects on liver regeneration. Colon resection positively influences liver regeneration, while ileum resection negatively influences the regenerative process, in a rat model.

ABSTRACT Purpose: To examine the effects of a negatively charged nanostructured curcumin microemulsion in experimental ulcerative colitis (UC) in rats. Methods: Four percent acetic acid was used to induce UC. The animals were treated for seven days and randomly assigned to four groups: normal control (NC), colitis/normal saline (COL/NS), colitis/curcumin (COL/CUR), and colitis/mesalazine (COL/MES). The nanostructured curcumin was formulated with a negative zeta potential (-16.70 ± 1.66 mV). Dosage of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin 1-β (IL-1β), interleukin 6 (IL-6), and antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase), macro and microscopic evaluation of the colon tissue were analyzed. Results: The COL/CUR group had a higher level of antioxidant enzymes compared to the COL/MESgroup. The levels of TNF-α, IL-1β and IL-6 were significantly lower in the colonic tissue of the COL/CUR group rats, when compared to the COL/NS and COL/MES groups (p < 0.001). The presence of ulcers in the colonic mucosa in rats of the COL/NSgroup was significantly higher than in the COL/MES group (p < 0.001). In the NC and COL/CUR groups, there were no ulcers in the colonic mucosa. Conclusions: The nanostructured microemulsion of curcumin, used orally, positively influenced the results of the treatment of UC in rats. The data also suggests that nanostructured curcumin with negative zeta potential is a promising phytopharmaceutical oral delivery system for UC therapy. Further research needs to be done to better understand the mechanisms of the negatively charged nanostructured curcumin microemulsion in UC therapy.

In this study, the chemical composition and antioxidant profile of five edible macroalgae, Fucus vesiculosus, Palmaria palmata, Porphyra dioica, Ulva rigida, and Gracilaria gracilis, cultivated in fully controlled closed systems, were determined. Protein, carbohydrates, and fat contents ranged between 12.4% and 41.8%, 27.6% and 42.0%, and 0.1% and 3.4%, respectively. The tested seaweeds presented considerable amounts of Ca, Mg, K, Mn, and Fe, which reinforce their favorable nutritional profile. Regarding their polysaccharide composition, Gracilaria gracilis and Porphyra dioica were rich in sugars common to agar-producing red algae, and Fucus vesiculosus was composed mainly of uronic acids, mannose, and fucose, characteristic of alginate and fucoidans, whereas rhamnose and uronic acid, characteristic of ulvans, predominated in Ulva rigida. Comparatively, the brown F. vesiculosus clearly stood out, presenting a high polysaccharide content rich in fucoidans, and higher total phenolic content and antioxidant scavenging activity, determined by DPPH and ABTS. The remarkable potential of these marine macroalgae makes them excellent ingredients for a wide range of health, food, and industrial applications.

Fucoidan has been reported to present diverse bioactivities, but each extract has specific features from which a particular biological activity, such as immunomodulation, must be confirmed. In this study a commercially available pharmaceutical-grade fucoidan extracted from Fucus vesiculosus, FE, was characterized and its anti-inflammatory potential was investigated. Fucose was the main monosaccharide (90 mol%) present in the studied FE, followed by uronic acids, galactose, and xylose that were present at similar values (3.8–2.4 mol%). FE showed a molecular weight of 70 kDa and a sulfate content of around 10%. The expression of cytokines by mouse bone-marrow-derived macrophages (BMDMs) revealed that the addition of FE upregulated the expression of CD206 and IL-10 by about 28 and 22 fold, respectively, in respect to control. This was corroborated in a stimulated pro-inflammatory situation, with the higher expression (60 fold) of iNOS being almost completely reversed by the addition of FE. FE was also capable of reverse LPS-caused inflammation in an in vivo mouse model, including by reducing macrophage activation by LPS from 41% of positive CD11C to 9% upon fucoidan injection. Taken together, the potential of FE as an anti-inflammatory agent was validated, both in vitro and in vivo.

In this paper we present a solution to a second order differential–difference equation that occurs in different contexts, specially in control engineering and finance. This equation leads to an ordinary differential equation, whose homogeneous part is a Cauchy–Euler equation. We derive a particular solution to this equation, presenting explicitly all the coefficients. The differential–difference equation is motivated by investment decisions addressed in the context of real options. It appears when the underlying stochastic process follows a jump-diffusion process, where the diffusion is a geometric Brownian motion and the jumps are driven by a Poisson process. The solution that we present - which takes into account the geometry of the problem - can be written backwards, and therefore its analysis is easier to follow.

Brown macroalgae are an important source of polysaccharides, mainly fucose-containing sulphated polysaccharides (FCSPs), associated with several biological activities. However, the structural diversity and structure–function relationships for their bioactivities are still undisclosed. Thus, the aim of this work was to characterize the chemical structure of water-soluble Saccharina latissima polysaccharides and evaluate their immunostimulatory and hypocholesterolemic activities, helping to pinpoint a structure–activity relationship. Alginate, laminarans (F1, neutral glucose-rich polysaccharides), and two fractions (F2 and F3) of FCSPs (negatively charged) were studied. Whereas F2 is rich in uronic acids (45 mol%) and fucose (29 mol%), F3 is rich in fucose (59 mol%) and galactose (21 mol%). These two fractions of FCSPs showed immunostimulatory activity on B lymphocytes, which could be associated with the presence of sulphate groups. Only F2 exhibited a significant effect in reductions in in vitro cholesterol’s bioaccessibility attributed to the sequestration of bile salts. Therefore, S. latissima FCSPs were shown to have potential as immunostimulatory and hypocholesterolemic functional ingredients, where their content in uronic acids and sulphation seem to be relevant for the bioactive and healthy properties.

Fucus vesiculosus is a brown seaweed with applications in the food, pharmaceutic, and cosmetic industries. Among its most valuable bioactive compounds are the pigment fucoxanthin and polysaccharides (e.g., fucoidans). In this study, we profiled the photosynthetic pigments and carbohydrates of F. vesiculosus from six locations along the Ílhavo Channel in the Iberian coastal lagoon of Ria de Aveiro, Portugal. Photosynthetic performance (Fv/Fm), pigment, and carbohydrate concentrations were similar between locations, despite differences in environmental factors, such as salinity and periods of exposure to desiccation. Concentration of total carbohydrates (neutral sugars + uronic acids) averaged 418 mg g−1 dw. Fucose was the second most abundant neutral sugar, with an average concentration of 60.7 mg g−1 dw, indicating a high content of fucoidans. Photosynthetic pigments included chlorophylls a and c, β,β-carotene, and the xanthophylls fucoxanthin, violaxanthin, antheraxanthin, and zeaxanthin. Concentrations of fucoxanthin were higher than those reported for most brown macroalgae, averaging 0.58 mg g−1 dw (65% of total carotenoids). This study indicates that F. vesiculosus from Ria de Aveiro is a valuable macroalgal resource for aquaculture companies operating in the region, with considerable potential to yield high-value bioactive compounds.

Cationic antimicrobial peptides (CAMPs) offer a promising strategy to counteract bacterial resistance, mostly due to their membrane-targeting activity. W-BP100 is a potent broad-spectrum cecropin-melittin CAMP bearing a single N-terminal Trp, which was previously found to improve its antibacterial activity. W-BP100 has high affinity toward anionic membranes, inducing membrane saturation at low peptide-to-lipid (P/L) ratios and membrane permeabilization, with the unique property of promoting the aggregation of anionic vesicles only at specific P/L ratios. Herein, we aimed to investigate this unusual behavior of W-BP100 by studying its aggregation and fusion properties with negatively-charged large (LUVs) or giant (GUVs) unilamellar vesicles using biophysical tools. Circular dichroism (CD) showed that W-BP100 adopted an α-helical conformation in anionic LUVs, neutralizing its surface charge at the aggregation P/L ratio. Its fusion activity, assessed by Förster resonance energy transfer (FRET) using steady-state fluorescence spectroscopy, occurred mainly at the membrane saturation/aggregation P/L ratio. Confocal microscopy studies confirmed that W-BP100 displays aggregation and detergent-like effects at a critical P/L ratio, above which it induces the formation of new lipid aggregates. Our data suggest that W-BP100 promotes the aggregation and fusion of anionic vesicles at specific P/L ratios, being able to reshape the morphology of GUVs into new lipid structures.

Coccolithophore microalgae, such as Emiliania huxleyi (EHUX) and Chrysotila pseudoroscoffensis (CP), are composed of calcium carbonate (CaCO3) and contain bioactive compounds that can be explored to produce sustainable food packaging. In this study, for the first time, these microalgae were incorporated as fillers in starch-based films, envisioning the development of biodegradable and bioactive materials for food packaging applications. The films were obtained by solvent casting using different proportions of the filler (2.5, 5, 10, and 20%, w/w). For comparison, commercial CaCO3, used as filler in the plastic industry, was also tested. The incorporation of CaCO3 and microalgae (EHUX or CP) made the films significantly less rigid, decreasing Young’s modulus up to 4.7-fold. Moreover, the incorporation of microalgae hydrophobic compounds as lipids turned the surface hydrophobic (water contact angles > 90°). Contrary to what was observed with commercial CaCO3, the films prepared with microalgae exhibited antioxidant activity, increasing from 0.9% (control) up to 60.4% (EHUX 20%) of ABTS radical inhibition. Overall, the introduction of microalgae biomass improved hydrophobicity and antioxidant capacity of starch-based films. These findings should be considered for further research using coccolithophores to produce active and sustainable food packaging material.

Chlorella vulgaris is a green microalga with a high chlorophyll content, representing a valuable source of green pigments for food applications. As the application of whole biomass can promote an unpleasant fish-like flavor, the use of chlorophyll extract can overcome this drawback. However, chlorophylls tend to easily degrade when out of the chloroplasts, decreasing their potential as a food ingredient. Thus, to study the suitable conditions for isolated chlorophylls preservation, in this work, the influence of temperature (4 to 60 °C), light (dark or 24 h photoperiod), alkaline conditions (with or without aqueous NaOH addition), and modified atmosphere (air or argon atmosphere) on the stability of the color in ethanolic solutions obtained from C. vulgaris were studied. The loss of green color with temperature followed the first-order kinetics, with an activation energy of 74 kJ/mol. Below 28 °C and dark conditions were suitable to preserve isolated chlorophylls. The addition of NaOH and an inert argon-rich atmosphere did not exhibit a statistically positive effect on color preservation. In the case study, cooked cold rice was colored to be used in sushi. The color remained stable for up to 3 days at 4 °C. Therefore, this work showed that C. vulgaris chlorophylls could be preserved in ethanolic solutions at room or lower temperatures when protected from light, allowing them to obtain a suitable natural food ingredient to color foodstuffs.

It is often found that a company has the opportunity to change its original production process to a different one. Here we consider two different situations: in the first one, the new production process may lead to larger losses (in case the demand decreases), but may also lead to larger profits (in case the demand increases); so we increase the risk. In the second one, the opposite holds (and we decrease the risk). We derive the optimal replacement strategy, and we study the impact of the drift and the volatility in the decision. Afterward, we include the option to exit the market and we compare both situations (with and without the exit option), concluding that in case the investment is in a less risky process, the impact of the exit option is different, depending on a relation involving the costs and the drift parameters.

ABSTRACT A multigene polysaccharide utilization locus (PUL) encoding enzymes and surface carbohydrate (glycan)-binding proteins (SGBPs) was recently identified in prominent members of Bacteroidetes in the human gut and characterized in Bacteroides ovatus. This PUL-encoded system specifically targets mixed-linkage β1,3-1,4-glucans, a group of diet-derived carbohydrates that promote a healthy microbiota and have potential as prebiotics. The BoSGBPMLG-A protein encoded by the BACOVA_2743 gene is a SusD-like protein that plays a key role in the PUL’s specificity and functionality. Here, we perform a detailed analysis of the molecular determinants underlying carbohydrate binding by BoSGBPMLG-A, combining carbohydrate microarray technology with quantitative affinity studies and a high-resolution X-ray crystallography structure of the complex of BoSGBPMLG-A with a β1,3-1,4-nonasaccharide. We demonstrate its unique binding specificity toward β1,3-1,4-gluco-oligosaccharides, with increasing binding affinities up to the octasaccharide and dependency on the number and position of β1,3 linkages. The interaction is defined by a 41-Å-long extended binding site that accommodates the oligosaccharide in a mode distinct from that of previously described bacterial β1,3-1,4-glucan-binding proteins. In addition to the shape complementarity mediated by CH-π interactions, a complex hydrogen bonding network complemented by a high number of key ordered water molecules establishes additional specific interactions with the oligosaccharide. These support the twisted conformation of the β-glucan backbone imposed by the β1,3 linkages and explain the dependency on the oligosaccharide chain length. We propose that the specificity of the PUL conferred by BoSGBPMLG-A to import long β1,3-1,4-glucan oligosaccharides to the bacterial periplasm allows Bacteroidetes to outcompete bacteria that lack this PUL for utilization of β1,3-1,4-glucans. IMPORTANCE With the knowledge of bacterial gene systems encoding proteins that target dietary carbohydrates as a source of nutrients and their importance for human health, major efforts are being made to understand carbohydrate recognition by various commensal bacteria. Here, we describe an integrative strategy that combines carbohydrate microarray technology with structural studies to further elucidate the molecular determinants of carbohydrate recognition by BoSGBPMLG-A, a key protein expressed at the surface of Bacteroides ovatus for utilization of mixed-linkage β1,3-1,4-glucans. We have mapped at high resolution interactions that occur at the binding site of BoSGBPMLG-A and provide evidence for the role of key water-mediated interactions for fine specificity and affinity. Understanding at the molecular level how commensal bacteria, such as prominent members of Bacteroidetes, can differentially utilize dietary carbohydrates with potential prebiotic activities will shed light on possible ways to modulate the microbiome to promote human health.

The major risk factor associated with the development of gastric cancer is chronic infection with Helicobacter pylori. The available treatments, based on a cocktail of antibiotics, fail in up to 40% of patients and disrupt their gut microbiota. The potential of blank nanostructured lipid carriers (NLC) for H. pylori eradication was previously demonstrated by us. However, the effect of NLC charge, size and protein corona on H. pylori-specific bactericidal activity herein studied was unknown at that time. All developed NLC formulations proved bactericidal against H. pylori. Although cationic NLC had 10-fold higher bactericidal activity than anionic NLC, they lacked specificity, since Lactobacillus acidophilus was also affected. Anionic NLC achieved complete clearance in both H. pylori morphologies (rod- and coccoid-shape) by inducing alterations in bacteria membranes and the cytoplasm, as visualized by transmission electron microscopy (TEM). The presence of an NLC protein corona, composed of 93% albumin, was confirmed by mass spectrometry. This protein corona delayed the bactericidal activity of anionic NLC against H. pylori and hindered NLC activity against Escherichia coli. Overall, these results sustain the use of NLC as a promising antibiotic-free strategy targeting H. pylori.

Ceftriaxone (CTX) a third-generation cephalosporin, is a broad-spectrum antibiotic that can be administered via intramuscular or intravenous routes to treat various types of infection. However, CTX has poor cellular penetration and poor diffusion due to its high molecular weight and high hydrophilicity. To address these problems, we propose an innovative nanotherapy based on the encapsulation of CTX in a nanostructured lipid carrier. Usually, several attempts must be made, on a trial-and-error basis, before a formulation that guarantees high drug encapsulation and suitable physicochemical properties is found. Machine Learning (ML) has recently stirred great interest as a tool to model and predict nanoparticles’ biological activity. Herein, for the first time, the use of ML for the optimization of a nanoformulation is explored. Several variables were optimized simultaneously, namely, the amount of solid lipid, the percentage of liquid lipid, the surfactant solution, the water volume, the sonication amplitude, and the sonication time. To define the best nanoformulation, three different outcomes were considered: the encapsulation efficiency of CTX, the size of the nanoparticles, and their zeta potential. Our ML approach was able to find, with a low number of experiments, the conditions that provided formulations with the highest encapsulation efficiency of CTX and nanoparticles with suitable size and adequate zeta potential. Besides the impressive acceleration of the optimization process that was achieved, the optimization guided by our ML model also provided insights into the optimization of other nanoformulations.

Chitosan–genipin (Ch-Ge) films have been proposed for the replacement of sulfur dioxide (SO2) in white wines preservation to circumvent the adverse health consequences caused by SO2 intake. To assess the effects of different-sized Ch-Ge films (25 and 100 cm2) on wine composition compared to SO2-treated and untreated wines, nuclear magnetic resonance metabolomics was applied. Relative to SO2, 100 cm2 films induced significant changes in the levels of organic acids, sugars, amino acids, 5-hydroxymethylfurfural, among other compounds, while 25 cm2 films appeared to induce only small variations. The observed metabolite variations were proposed to arise from the mitigation of fermentative processes, electrostatic interactions between acids and the positively charged films and the promotion of Maillard and Strecker reactions. Qualitative sensory analysis showed that wines maintained overall appropriate sensory characteristics, with 100 cm2 film treated wines showing slightly higher attributes. Based on these results, the possibility of using Ch-Ge films as a replacement for SO2 treatment is discussed.

Bacterial biofilms of Staphylococcus aureus, formed on implants, have a massive impact on the increasing number of antimicrobial resistance cases. The current treatment for biofilm-associated infections is based on the administration of antibiotics, failing to target the biofilm matrix. This work is focused on the development of multiple lipid nanoparticles (MLNs) encapsulating the antibiotic moxifloxacin (MOX). The nanoparticles were functionalized with d-amino acids to target the biofilm matrix. The produced formulations exhibited a mean hydrodynamic diameter below 300 nm, a low polydispersity index, and high encapsulation efficiency. The nanoparticles exhibited low cytotoxicity towards fibroblasts and low hemolytic activity. To target bacterial cells and the biofilm matrix, MOX-loaded MLNs were combined with a nanosystem encapsulating a matrix-disruptive agent: N-acetyl-L-cysteine (NAC). The nanosystems alone showed a significant reduction of both S. aureus biofilm viability and biomass, using the microtiter plate biofilm model. Further, biofilms grown inside polyurethane catheters were used to assess the effect of combining MOX-loaded and NAC-loaded nanosystems on biofilm viability. An increased antibiofilm efficacy was observed when combining the functionalized MOX-loaded MLNs and NAC-loaded nanosystems. Thus, nanosystems as carriers of bactericidal and matrix-disruptive agents are a promising combinatory strategy towards the eradication of S. aureus biofilms.

Abstract Background Flavonoids are produced in all flowering plants in a wide range of tissues including in berry fruits. These compounds are of considerable interest for their biological activities, health benefits and potential pharmacological applications. However, transcriptomic and genomic resources for wild and cultivated berry fruit species are often limited, despite their value in underpinning the in-depth study of metabolic pathways, fruit ripening as well as in the identification of genotypes rich in bioactive compounds. Results To access the genetic diversity of wild and cultivated berry fruit species that accumulate high levels of phenolic compounds in their fleshy berry(-like) fruits, we selected 13 species from Europe, South America and Asia representing eight genera, seven families and seven orders within three clades of the kingdom Plantae. RNA from either ripe fruits (ten species) or three ripening stages (two species) as well as leaf RNA (one species) were used to construct, assemble and analyse de novo transcriptomes. The transcriptome sequences are deposited in the BacHBerryGEN database (http://jicbio.nbi.ac.uk/berries) and were used, as a proof of concept, via its BLAST portal (http://jicbio.nbi.ac.uk/berries/blast.html) to identify candidate genes involved in the biosynthesis of phenylpropanoid compounds. Genes encoding regulatory proteins of the anthocyanin biosynthetic pathway (MYB and basic helix-loop-helix (bHLH) transcription factors and WD40 repeat proteins) were isolated using the transcriptomic resources of wild blackberry (Rubus genevieri) and cultivated red raspberry (Rubus idaeus cv. Prestige) and were shown to activate anthocyanin synthesis in Nicotiana benthamiana. Expression patterns of candidate flavonoid gene transcripts were also studied across three fruit developmental stages via the BacHBerryEXP gene expression browser (http://www.bachberryexp.com) in R. genevieri and R. idaeus cv. Prestige. Conclusions We report a transcriptome resource that includes data for a wide range of berry(-like) fruit species that has been developed for gene identification and functional analysis to assist in berry fruit improvement. These resources will enable investigations of metabolic processes in berries beyond the phenylpropanoid biosynthetic pathway analysed in this study. The RNA-seq data will be useful for studies of berry fruit development and to select wild plant species useful for plant breeding purposes.

A handful of sea slugs of the order Sacoglossa are able to steal chloroplasts—kleptoplasts—from their algal food sources and maintain them functionally for periods ranging from several weeks to a few months. In this study, we investigated the role of kleptoplast photosynthesis on mucus production by the tropical sea slug Elysia crispata. Animals reared for 5 weeks in quasi dark (5 μmol photons m−2 s−1) showed similar growth to those under regular light (60–90 μmol photons m−2 s−1), showing that kleptoplast photosynthesis was not relevant for growth when sea slugs were fed ad libitum. However, when subjected to short-term desiccation stress, animals reared under regular light produced significantly more mucus. Furthermore, the carbohydrate content of secreted mucus was significantly lower in slugs limited in the photosynthetic activity of their kleptoplasts by quasi-dark conditions. This study indicates that photosynthesis supports the synthesis of protective mucus in kleptoplast-bearing sea slugs.

Inflammatory bowel diseases (IBD) with chronic infiltration of immune cells in the gastrointestinal tract are common and largely incurable. The therapeutic targeting of IBD has been hampered by the complex causality of the disease, with environmental insults like cholesterol-enriched Western diets playing a critical role. To address this drug development challenge, we report an easy-to-handle dietary cholesterol-based in vivo assay that allows the screening of immune-modulatory therapeutics in transgenic zebrafish models. An improvement in the feeding strategy with high cholesterol diet (HCD) selectively induces a robust and consistent infiltration of myeloid cells in larvae intestines that is highly suitable for compound discovery efforts. Using transgenics with fluorescent reporter expression in neutrophils, we take advantage of the unique zebrafish larvae clarity to monitor an acute inflammatory response in a whole organism context with a fully functional innate immune system. The use of semi-automated image acquisition and processing combined with quantitative image analysis allows categorizing anti- or pro-inflammatory compounds based on a leukocytic inflammation index. Our HCD gut inflammation (HCD-GI) assay is simple, cost- and time-effective as well as highly physiological which makes it unique when compared to chemical-based zebrafish models of IBD. Besides, diet is a highly controlled, selective and targeted trigger of intestinal inflammation that avoids extra-intestinal outcomes and reduces the chances of chemical-induced toxicity during screenings. We show the validity of this assay for a screening platform by testing two dietary phenolic acids, namely gallic acid (GA; 3,4,5-trihydroxybenzoic acid) and ferulic acid (FA; 4-hydroxy-3-methoxycinnamic acid), with well described anti-inflammatory actions in animal models of IBD. Analysis of common IBD therapeutics (Prednisolone and Mesalamine) proved the fidelity of our IBD-like intestinal inflammation model. In conclusion, the HCD-GI assay can facilitate and accelerate drug discovery efforts on IBD, by identification of novel lead molecules with immune modulatory action on intestinal neutrophilic inflammation. This will serve as a jumping-off point for more profound analyses of drug mechanisms and pathways involved in early IBD immune responses.

Bivalves are widely distributed through diverse habitats, including estuaries and coastal lagoons which are extremely productive ecosystems, and play important roles in trophic webs and in ecosystems’ biological processes. Bivalves, as well as other marine resources, have been a part of the humans’ diet since mankind started fishing. These resources have high nutritional values, being constituted by high protein and low fat contents, and its consumption is associated with several health benefits. Marine resources, like bivalves, that are highly appreciated by humans, represent an important economic value, being under pressure due to an increasing demand. Thus, it is important a sustainable and balanced exploitation of these resources, based on the knowledge of the biochemical composition of the aquatic species to comprehend its’ potential and nutritional value.The present study was conducted in Portugal, a country that has one of the highest consumptions of seafood in the world. Six commercially valuable species of marine bivalves were harvested in two distinct areas, Mondego estuary and Ria Formosa lagoon, and in two seasons, winter 2016 and summer 2017. The aims of the study were to: 1) determine the biochemical composition of each species in terms of total protein content, fatty acid and carbohydrate profiles; 2) identify potential spatial and seasonal variations between bivalve species sampled in each study area and season; 3) assess feeding behaviour of the bivalve species in both seasons and study areas.The results indicated diverse biochemical composition among bivalve species, with total protein as the major component, followed by fatty acid content, particularly by the essential fatty acids DHA and EPA, and glycogen and glucose as the main polysaccharide and monosaccharide, respectively, found in all specimens. In general, all species demonstrated a tendency for omnivory, with only S. marginatus presenting a clear herbivorous behaviour in summer. Despite M. galloprovincialis and R. decussatus showed the highest nutritional value in the Mondego estuary, in both seasons, it was more noticeable in winter. In Ria Formosa, C. edule and R. decussatus showed the highest nutritious value in both seasons, while C. gigas showed higher nutritive value in summer.

Summary: Impairment of the p53 pathway is a critical event in cancer. Therefore, reestablishing p53 activity has become one of the most appealing anticancer therapeutic strategies. Here, we disclose the p53-activating anticancer drug (3S)-6,7-bis(hydroxymethyl)-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazole (MANIO). MANIO demonstrates a notable selectivity to the p53 pathway, activating wild-type (WT)p53 and restoring WT-like function to mutant (mut)p53 in human cancer cells. MANIO directly binds to the WT/mutp53 DNA-binding domain, enhancing the protein thermal stability, DNA-binding ability, and transcriptional activity. The high efficacy of MANIO as an anticancer agent toward cancers harboring WT/mutp53 is further demonstrated in patient-derived cells and xenograft mouse models of colorectal cancer (CRC), with no signs of undesirable side effects. MANIO synergizes with conventional chemotherapeutic drugs, and in vitro and in vivo studies predict its adequate drug-likeness and pharmacokinetic properties for a clinical candidate. As a single agent or in combination, MANIO will advance anticancer-targeted therapy, particularly benefiting CRC patients harboring distinct p53 status.

Abstract Purpose The objective of this study was to investigate the accuracy of 18F-FDG-PET in the diagnosis of multibacterial abdominal sepsis by cecum ligation and puncture (CLP) in rats. Methods Adult Wistar rats ( Rattus norvegicus ), weighing 227±35g, were allocated into a sepsis group by CLP (n=10) and sham group (n=10). 18F-FDG-PET using microPET was performed on all rats after 24 hours. Results All animals survived for postoperative 24h. The abdomen/liver ratio of the standardized uptake value (SUV) percentage was significantly higher in the sepsis group than in the sham (p=0.004). The ROC curve showed an accuracy of 18F-FDG-PET to detect abdominal sepsis of 88.9% (p=0.001), sensitivity of 90% and specificity of 88.9%. When a cut-off point of 79% of the ratio between the SUV on the abdominal region and liver was established, the sensitivity was 90%, specificity of 88.9%; positive and negative predictive values of 90.0% and 88.9%, respectively. Conclusions The diagnostic accuracy of 18F-FDG-PET in rats with abdominal sepsis was significantly high. It was also demonstrated the predictive ability of the abdomen/liver SUV ratio to diagnose abdominal sepsis. These findings may have implications for the clinical setting, locating septic foci with PETscan.

Bacterial biofilms represent a major concern at a worldwide level due to the high demand for implantable medical devices and the rising numbers of bacterial resistance. The complex structure of the extracellular polymeric substances (EPS) matrix plays a major role in this phenomenon, since it protects bacteria from antibiotics, avoiding drug penetration at bactericidal concentrations. Besides, this structure promotes bacterial cells to adopt a dormant lifestyle, becoming less susceptible to antibacterial agents. Currently, the available treatment for biofilm-related infections consists in the administration of conventional antibiotics at high doses for a long-term period. However, this treatment lacks efficiency against mature biofilms and for implant-associated biofilms it may be necessary to remove the medical device. Thus, biofilm-related infections represent an economical burden for the healthcare systems. New strategies focusing on the matrix are being highlighted as alternative therapies to eradicate biofilms. Here, we outline reported matrix disruptive agents, nanocarriers, and technologies, such as application of magnetic fields, photodynamic therapy, and ultrasounds, that have been under investigation to disrupt the EPS matrix of clinically relevant bacterial biofilms. In an ideal therapy, a synergistic effect between antibiotics and the explored innovated strategies is aimed to completely eradicate biofilms and avoid antimicrobial resistance phenomena.

In the last years, microneedles (MNs) have been considered a valuable, painless, and minimally invasive approach for controlled transdermal drug delivery (TDD). Rivastigmine (RV), a drug administered to patients suffering from dementia, is currently delivered by oral or transdermal routes; however, both present limitations, mainly gastrointestinal adverse symptoms or local skin irritation and drug losses, respectively, for each route. Given this, the objective of the present work was to develop and evaluate the potential of polymeric MNs for RV transdermal delivery in a controlled manner. Polymeric MNs with two needle heights and different compositions were developed with calcein as a fluorescent model molecule. Morphology and mechanical characterisation were accessed. Skin permeation experiments showed the ability of the devices to deliver calcein and confirmed that the arrays were able to efficiently pierce the skin. To obtain a new TDD anti-dementia therapeutic solution, RV was loaded in 800 µm polymeric MNs of alginate and alginate/k-carrageenan MNs. In the presence of RV, the MN’s morphology was maintained; however, the presence of RV influenced the compression force. Skin permeation studies revealed that RV-loaded MNs allowed a more efficient controlled release of the drug than the commercial patch. In vivo, skin irritation tests in rabbits revealed that the developed MNs were innocuous upon removal, in contrast with the evidence found for Exelon®, the commercial patch, which caused slight mechanical damage to the skin. The herein-produced MNs demonstrated a more controlled release of the drug, being the more suitable option for the transdermal delivery of RV.

The low solubility of active pharmaceutical ingredients (APIs) is a problem in pharmaceutical development. Several methodologies can be used to improve API solubility, including the use of eutectic systems in which one of the constituents is the API. This class of compounds is commonly called Therapeutic Deep Eutectic Systems (THEDES). THEDES has been gaining attention due to their properties such as non-toxicity, biodegradability, and being non-expensive and easy to prepare. Since the knowledge of the solid liquid diagram of the mixture and the ideal eutectic point is necessary to ascertain if a mixture is a deep eutectic or just a eutectic mixture that is liquid at ambient temperature, the systems studied in this work are called Therapeutic Liquid Eutectic Systems (THELES). Therefore, the strategy proposed in this work is to improve the solubility of chlorpropamide and tolbutamide by preparing THELES. Both APIs are sulfonylurea compounds used for the treatment of type 2 diabetes mellitus and have low solubility in water. To prepare the THELES, several coformers were tested, namely, tromethamine, L(+)-arginine, L-tryptophan, citric acid, malic acid, ascorbic acid, and p-aminobenzoic acid, in molar ratios of 1:1 and 1:2. To improve viscosity, water was added in different molar ratios to all systems. THELES were characterized by mid-infrared spectroscopy (MIR), and differential scanning calorimetry. Their viscosity, solubility, and permeability were also determined. Their stability at room temperature and 40 °C was accessed by MIR. Cytocompatibility was performed by metabolic activity and cell lysis evaluation, according to ISO10993-5:2009, and compared with the crystalline APIs. THELES with TRIS were successfully synthesized for both APIs. Results showed an increased solubility without a decrease in the permeability of the APIs in the THELES when compared with the pure APIs. The THELES were also considered stable for 8 weeks at ambient temperature. The cells studied showed that the THELES were not toxic for the cell lines used.

Magnetic nanoparticles (NP), such as magnetite, have been the subject of research for application in the biomedical field, especially in Magnetic Hyperthermia Therapy (MHT), a promising technique for cancer therapy. NP are often coated with different compounds such as natural or synthetic polymers to protect them from oxidation and enhance their colloidal electrostatic stability while maintaining their thermal efficiency. In this work, the synthesis and characterization of magnetite nanoparticles coated with fucoidan, a biopolymer with recognized biocompatibility and antitumoral activity, is reported. The potential application of NP in MHT was evaluated through the assessment of Specific Loss Power (SLP) under an electromagnetic field amplitude of 14.7 kA m−1 and at 276 kHz. For fucoidan-coated NP, it was obtained SLP values of 100 and 156 W/g, corresponding to an Intrinsic Loss Power (ILP) of 1.7 and 2.6 nHm2kg−1, respectively. These values are, in general, higher than the ones reported in the literature for non-coated magnetite NP or coated with other polymers. Furthermore, in vitro assays showed that fucoidan and fucoidan-coated NP are biocompatible. The particle size (between ca. 6 to 12 nm), heating efficiency, and biocompatibility of fucoidan-coated magnetite NP meet the required criteria for MHT application.

Niacinamide (NIA) has been widely used in halting the features of ageing by acting as an antioxidant and preventing dehydration. NIA’s physicochemical properties suggest difficulties in surpassing the barrier imposed by the stratum corneum layer to reach the target in the skin. To improve cutaneous delivery of NIA, a hybrid nanogel was designed using carrageenan and polyvinylpyrrolidone polymers combined with jojoba oil as a permeation enhancer. Three different types of transethosomes were prepared by the thin-film hydration method, made distinct by the presence of either an edge activator or a permeation enhancer, to allow for a controlled delivery of NIA. Formulations were characterized by measurements of size, polydispersity index, zeta potential, encapsulation efficiency, and loading capacity, and by evaluating their chemical interactions and morphology. Skin permeation assays were performed using Franz diffusion cells. The hybrid hydrogels exhibited robust, porous, and highly aligned macrostructures, and when present, jojoba oil changed their morphology. Skin permeation studies with transethosomes-loaded hydrogels showed that nanogels per se exhibit a more controlled and enhanced permeation, in particular when jojoba oil was present in the transethosomes. These promising nanogels protected the human keratinocytes from UV radiation, and thus can be added to sunscreens or after-sun lotions to improve skin protection.

Hyaluronic acid (HA) is a natural polymer, produced endogenously by the human body, which has unique physicochemical and biological properties, exhibiting desirable biocompatibility and biodegradability. Therefore, it has been widely studied for possible applications in the area of inflammatory diseases. Although exogenous HA has been described as unable to restore or replace the properties and activities of endogenous HA, it can still provide satisfactory pain relief. This review aims to discuss the advances that have been achieved in the treatment of inflammatory diseases using hyaluronic acid as a key ingredient, essentially focusing on studies carried out between the years 2017 and 2021.

Multi-segmented bilayered Fe/Cu nanowires have been fabricated through the electrodeposition in porous anodic alumina membranes. We have assessed, with the support of micromagnetic simulations, the dependence of fabricated nanostructures’ magnetic properties either on the number of Fe/Cu bilayers or on the length of the magnetic layers, by fixing both the nonmagnetic segment length and the wire diameter. The magnetic reversal, in the segmented Fe nanowires (NWs) with a 300 nm length, occurs through the nucleation and propagation of a vortex domain wall (V-DW) from the extremities of each segment. By increasing the number of bilayers, the coercive field progressively increases due to the small magnetostatic coupling between Fe segments, but the coercivity found in an Fe continuous nanowire is not reached, since the interactions between layers is limited by the Cu separation. On the other hand, Fe segments 30 nm in length have exhibited a vortex configuration, with around 60% of the magnetization pointing parallel to the wires’ long axis, which is equivalent to an isolated Fe nanodisc. By increasing the Fe segment length, a magnetic reversal occurred through the nucleation and propagation of a V-DW from the extremities of each segment, similar to what happens in a long cylindrical Fe nanowire. The particular case of the Fe/Cu bilayered nanowires with Fe segments 20 nm in length revealed a magnetization oriented in opposite directions, forming a synthetic antiferromagnetic system with coercivity and remanence values close to zero.

Acrylamide (AA) is a food contaminant in thermally processed products that is object of tight control. A simple and easy-to-apply methodology for routine monitoring of AA levels in food products could allow producers to be players in the control of their own products. In this work, a simple methodology for AA quantification without derivatization was developed for biscuits, for which the benchmark levels recommended by EFSA are 350 µg/kg, and 150 µg/kg for biscuits for infants and young children. Headspace-solid phase microextraction (HS-SPME) was used in 120 mL screwed-cap vials with a carboxen/polydimetylsiloxane fiber, 4 g of biscuits, and 10 mL of water during 15 min at room temperature under stirring. The addition of 30 mL of propanol under stirring during 15 min at room temperature and 15 min at 60 °C was used to promote AA transfer to the headspace. The fiber exposure was 45 min. A gas chromatography-mass spectrometry analysis allowed to obtain an external calibration curve at m/z 71, with linearity R2 > 0.99 and precision RSD < 9%. The detection and quantification limits were 27.4 µg/kg and 91.5 µg/kg, respectively. The methodology was successfully used in biscuits with lower AA amount, where mitigation strategies (asparaginase or pectate) were applied.

Inflammatory bowel disease (IBD) is a group of disabling, destructive and incurable immune-mediated inflammatory diseases comprising Crohn’s disease (CD) and ulcerative colitis (UC), disorders that are highly prevalent worldwide and demand a large investment in healthcare. A persistent inflammatory state enables the dysfunction and destruction of healthy tissue, hindering the initiation and endurance of wound healing. Current treatments are ineffective at counteracting disease progression. Further, increased risk of serious side effects, other comorbidities and/or opportunistic infections highlight the need for effective treatment options. Gut microbiota, the key to preserving a healthy state, may, alternatively, increase a patient’s susceptibility to IBD onset and development given a relevant bacterial dysbiosis. Hence, the main goal of this review is to showcase the main conventional and emerging therapies for IBD, including microbiota-inspired untargeted and targeted approaches (such as phage therapy) to infection control. Special recognition is given to existing targeted strategies with biologics (via monoclonal antibodies, small molecules and nucleic acids) and stimuli-responsive (pH-, enzyme- and reactive oxygen species-triggered release), polymer-based nanomedicine that is specifically directed towards the regulation of inflammation overload (with some nanosystems additionally functionalized with carbohydrates or peptides directed towards M1-macrophages). The overall goal is to restore gut balance and decrease IBD’s societal impact.

The diversity of zinc oxide (ZnO) particles and derived composites applications is highly dependent on their structure, size, morphology, defect amounts, and/or presence of dopant molecules. In this work, ZnO nanostructures are grown in situ on graphene oxide (GO) sheets by an easily implementable solvothermal method with simultaneous reduction of GO. The effect of two zinc precursors (zinc acetate (ZA) and zinc acetate dihydrate (ZAD)), NaOH concentration (0.5, 1 or 2 M), and concentration (1 and 12.5 mg/mL) and pH (pH = 1, 4, 8, and 12) of GO suspension were evaluated. While the ZnO particle morphology shows to be precursor dependent, the average particle size length decreases with lower NaOH concentration, as well as with the addition of a higher basicity and concentration of GO suspension. A lowered band gap and a higher specific surface area are obtained from the ZnO composites with higher amounts of GO suspension. Otherwise, the low concentration and the higher pH of GO suspension induce more lattice defects on the ZnO crystal structure. The role of the different condition parameters on the ZnO nanostructures and their interaction with graphene sheets was observed to tune the ZnO–rGO nanofiller properties for photocatalytic and antimicrobial activities.

Chitosan-genipin films have been proposed for preservation of white wine, maintaining their varietal key odorants and organoleptic characteristics of sulfur dioxide treated wines. Nevertheless, these wines showed aroma notes that slightly distinguish them. It is possible that during the contact of films with wine for at least 2 months, after fermentation and prior to bottling, interactions or chemical reactions are promoted. In this work, wine model solutions with volatile compounds in contact with chitosan-genipin films were performed to evaluate their evolution along time. To complement these analyses, the volatile compounds of white and red wines kept in contact with chitosan-genipin films during 2 and 8 months were also studied. The results obtained allowed us to conclude that the contact of chitosan-genipin films with both white and red wines tend to retain long carbon chain volatile compounds, such as ethyl hexanoate and octan-3-one. It also promoted the formation of Maillard reaction products, such as furfural by dehydration of pentoses and Strecker aldehydes, such as 3-methylbutanal and phenylacetaldehyde, by degradation of amino acids. This study reveals that the use of chitosan-genipin films for wine preservation is also able to promote the formation of compounds that can modulate the wines aroma, maintaining the varietal notes.

Several classes of polysaccharides have been described to have hypocholesterolemic potential, namely cholesterol bioaccessibility and bioavailability. This review will highlight the main mechanisms by which polysaccharides are known to affect cholesterol homeostasis at the intestine, namely the effect (i) of polysaccharide viscosity and its influence on cholesterol bioaccessibility; (ii) on bile salt sequestration and its dependence on the structural diversity of polysaccharides; (iii) of bio-transformations of polysaccharides and bile salts by the gut microbiota. Different quantitative structure–hypocholesterolemic activity relationships have been explored depending on the mechanism involved, and these were based on polysaccharide physicochemical properties, such as sugar composition and ramification degree, linkage type, size/molecular weight, and charge. The information gathered will support the rationalization of polysaccharides’ effect on cholesterol homeostasis and highlight predictive rules towards the development of customized hypocholesterolemic functional food.

Parkinson’s disease (PD) is an age-related neurodegenerative disorder associated with the misfolding and aggregation of alpha-synuclein (aSyn) in proteinaceous inclusions. These inclusions are common to a wider spectrum of disorders known as synucleinopathies. While the molecular bases of PD are still unclear, oxidative stress and impairment of protein quality-control systems play an important role, and are regarded as valuable targets for therapeutic interventions. We employed a yeast model of synucleinopathies to test the cytoprotective potential of phycocyanin, a biliprotein used as a nutritional supplement. We found that phycocyanin effectively protected against aSyn toxicity in yeast and, importantly, the mechanism of action involves the reduction of aSyn inclusions and superoxide levels, through the regulation of genes and enzymes involved in oxidative stress response, glutathione metabolism, and cellular protein quality-control systems. Overall, this study highlights the potential of phycocyanin as a nutraceutical in neurodegenerative diseases associated with proteotoxicity, such as synucleinopathies.

Abstract Despite doxorubicin being commonly used in chemotherapy there still remain significant holes in our knowledge regarding its delivery efficacy and an observed resistance mechanism that is postulated to involve the cell membrane. One possible mechanism is the efflux by protein P-gp, which is found predominantly in cholesterol enriched domains. Thereby, a hypothesis for the vulnerability of doxorubicin to efflux through P-gp is its enhanced affinity for the ordered cholesterol rich regions of the plasma membrane. Thus, we have studied doxorubicin’s interaction with model membranes in a cholesterol rich, ordered environment and in liquid-disordered cholesterol poor environment. We have combined three separate experimental protocols: UV-Vis spectrophotometry, fluorescence quenching and steady-state anisotropy and computational molecular dynamics modeling. Our results show that the presence of cholesterol induces a change in membrane structure and doesn’t impair doxorubicin’s membrane partitioning, but reduces drug’s influence on membrane fluidity without directly interacting with it. It is thus possible that the resistance mechanism that lowers the efficacy of doxorubicin, results from an increased density in membrane regions where the efflux proteins are present. This work represents a successful approach, combining experimental and computational studies of membrane based systems to unveil the behavior of drugs and candidate drug molecules.

Abstract The present study aims to assess the plastic response of Zostera noltei meadows traits under spatio-temporal shifts in salinity combined with sediment environmental variables (temperature; pH; loss-on-ignition (LOI); carbon (C) and nitrogen (N) pools (top 5 cm)). Z. noltei biomass, C and N pools, leaf photosynthetic performance and esterified fatty acid (FA) profile were assessed within a temperate coastal lagoon during winter and late spring, along sites spatially distributed. None of the surveyed traits for Z. noltei displayed a clear spatial trend. Z. noltei proved to be euryhaline, whose biology was only slightly affected within this salinity range, in each season (14–39 in winter; 33–41 in late spring). Seasonal differences in salinity and environmental parameters explain the differences recorded in Z. noltei traits (aboveground biomass, N and C pools; photosynthetic performance). Spatio-temporal salinity shifts did not significantly affect the pool of FA present in Z. noltei. Overall, within the salinity range surveyed, the ecological processes studied and regulating Z. noltei meadows do not appear to be at risk. This work reinforces the plasticity of Z. noltei to salinity shifts within the studied range, with this finding being particularly relevant in the context of extreme weather events (e.g., winter freshwater floods, summer droughts).

Abstract Purpose: To evaluate the effect of tadalafil in renal ischemia/reperfusion (I/R) injury in rats Methods: Group I/R saline rats (n=6) were subjected to 45 minutes of left renal ischemia and treated with saline; the I/R tadalafil rats (n=6) received oral 10mg/kg tadalafil microemulsion one hour before ischemia. In both groups, 8 hours after ischemia, laboratory analysis were performed Results: Better tissue perfusion was lower in ischemic left/kidney than in right/kidney in saline group, suggesting reduced kidney clearance. Fluorescence in left/kidneys of tadalafil treated rats was lower than in right/kidneys (difference not significant). The fluorescence signal intensity in kidneys of tadafil treated rats was higher than in saline rats. TNF-α levels were significantly lower in I/R tadalafil group rats compared to I/R saline group (154±10.3 vs 391.3±12.3), as well as IL-1β (163.4±13.2 vs 279±11.5pg/dL), and IL-6 (122.9±8.1 vs 173.7±6.3 respectively; p=0.0001). Urea, creatinine and C-reactive protein were significantly lower in tadafil treated rats then in saline group Conclusion: Tadalafil therapy decreased the expression of circulating pro-inflammatory cytokines in a renal I/R rodent model, while improving kidney function proofs.

O artigo procura apontar caminhos e possibilidades de pesquisa sobre Sergipe no pós-abolição, traçando um painel amplo e multifacetado das experiências de libertos e seus descendentes no plano do trabalho, da moradia, da sociabilidade, do lazer, enfim, no plano do cotidiano. A partir da documentação do Arquivo do Judiciário, sobretudo, reconstituiremos aspectos da complexa vida desses sujeitos negligenciados pela historiografia até recentemente.

Abstract Purpose: To examine the effects of Arrabidaa chica (Bignoniacea) extract, a native plant of the Amazon known as crajiru, on a 7,12-dimethyl-1,2-benzanthracene (DMBA)-induced breast cancer model in Wistar rats. Methods: We compared the response of breast cancer to the oral administration of A. chica extract (ACE) for 16 weeks, associated or not with vincristine. Groups: normal control; DMBA (50mg/kg v.o,) without treatment; DMBA+ACE (300 mg/kg); DMBA+vincristine. 500μg/kg injected i.p; DMBA+ACE+Vincristine 250μg/kg i.p. Imaging by microPET and fluorescence, biochemistry, oxidative stress, hematology and histopathology were used to validate the treatments. Results: All animals survived. A gradual weight gain in all groups was observed, with no significant difference (p>0.05). The oral administration of ACE and ACE+vincristine 50% significantly reduced breast tumors incidence examined with PET-18FDG and fluorescence (p

Lauric acid (LAH) strongly inhibits the growth of acne-causing bacteria. LAH is essentially water-insoluble and the solubility of laurate (LA) salts are medium and temperature dependent. Hence, LAH/LA preparations are difficult to formulate. Here we fully characterized phospholipid vesicles containing up to 50 mol% LAH. Vesicles of dipalmitoylphosphatidylcholine (DPPC) containing LAH, at pHs 7.4 and 5.0, were characterized measuring size, charge, bilayer phase transition temperature (Tm) and permeability of water-soluble probes. Small angle X-ray scattering and cryotransmission electron microscopy showed multilamellar vesicles at low LAH %. Increasing LAH % had a negligible effect on particle size. An internal aqueous compartment in all vesicle's preparations, even at equimolar DPPC: LAH fractions, was demonstrated using water-soluble probes. At pH 5.0, the interaction between DPPC and LAH increased the Tm and phase transition cooperativity showing a single lipid phase formed by hydrogen-bonded DPPC: LAH complexes. At pH 7.4, vesicles containing 50 mol% LAH exhibited distinct phases, ascribed to complex formation between LAH and LA or LAH and DPPC. LAH incorporated in the vesicles minimally permeated a skin preparation at both pHs, indicating that the primary sites of LAH solubilization were the skin layers. These results provide the foundations for developing processes and products containing DPPC: LAH.

Phenolic compounds are thought to be important to prevent neurodegenerative diseases (ND). Parkinson’s Disease (PD) is a neurodegenerative disorder known for its typical motor features, the deposition of α-synuclein (αsyn)-positive inclusions in the brain, and for concomitant cellular pathologies that include oxidative stress and neuroinflammation. Neuroprotective activity of fisetin, a dietary flavonoid, was evaluated against main hallmarks of PD in relevant cellular models. At physiologically relevant concentrations, fisetin protected SH-SY5Y cells against oxidative stress overtaken by tert-butyl hydroperoxide (t-BHP) and against methyl-4-phenylpyridinuim (MPP+)-induced toxicity in dopaminergic neurons, the differentiated Lund human Mesencephalic (LUHMES) cells. In this cellular model, fisetin promotes the increase of the levels of dopamine transporter. Remarkably, fisetin reduced the percentage of cells containing αsyn inclusions as well as their size and subcellular localization in a yeast model of αsyn aggregation. Overall, our data show that fisetin exerts modulatory activities toward common cellular pathologies present in PD; remarkably, it modulates αsyn aggregation, supporting the idea that diets rich in this compound may prove beneficial.

Inflammation is a crucial and complex process that reestablishes the physiological state after a noxious stimulus. In pathological conditions the inflammatory state may persist, leading to chronic inflammation and causing tissue damage. Sesquiterpene lactones (SLs) are composed of a large and diverse group of highly bioactive plant secondary metabolites, characterized by a 15-carbon backbone structure. In recent years, the interest in SLs has risen due to their vast array of biological activities beneficial for human health. The anti-inflammatory potential of these compounds results from their ability to target and inhibit various key pro-inflammatory molecules enrolled in diverse inflammatory pathways, and prevent or reduce the inflammatory damage on tissues. Research on the anti-inflammatory mechanisms of SLs has thrived over the last years, and numerous compounds from diverse plants have been studied, using in silico, in vitro, and in vivo assays. Besides their anti-inflammatory potential, their cytotoxicity, structure–activity relationships, and pharmacokinetics have been investigated. This review aims to gather the most relevant results and insights concerning the anti-inflammatory potential of SL-rich extracts and pure SLs, focusing on their effects in different inflammatory pathways and on different molecular players.

Cichorium intybus L. or chicory plants are a natural source of health-promoting compounds in the form of supplements such as inulin, as well as other bioactive compounds such as sesquiterpene lactones (SLs). After inulin extraction, chicory roots are considered waste, with most SLs not being harnessed. We developed and optimized a new strategy for SL extraction that can contribute to the conversion of chicory root waste into valuable products to be used in human health-promoting applications. In our work, rich fractions of SLs were recovered from chicory roots using supercritical CO2. A response surface methodology was used to optimize the process parameters (pressure, temperature, flow rate, and co-solvent percentage) for the extraction performance. The best operating conditions were achieved at 350 bar, 40 °C, and 10% EtOH as a co-solvent in a 15 g/min flow rate for 120 min. The extraction with supercritical CO2 revealed to be more selective for the SLs than the conventional solid–liquid extraction with ethyl acetate. In our work, 1.68% mass and a 0.09% sesquiterpenes yield extraction were obtained, including the recovery of two sesquiterpene lactones (8-deoxylactucin and 11β,13-dihydro-8-deoxylactucin), which, to the best of our knowledge, are not commercially available. A mixture of the abovementioned compounds were tested at different concentrations for their toxic profile and anti-inflammatory potential towards a human calcineurin/NFAT orthologue pathway in a yeast model, the calcineurin/Crz1 pathway. The SFE extract obtained, rich in SLs, yielded results of inhibition of 61.74 ± 6.87% with 50 µg/mL, and the purified fraction containing 8-deoxylactucin and 11β,13-dihydro-8-deoxylactucin inhibited the activation of the reporter gene up to 53.38 ± 3.9% at 10 µg/mL. The potential activity of the purified fraction was also validated by the ability to inhibit Crz1 nuclear translocation and accumulation. These results reveal a possible exploitable green technology to recover potential anti-inflammatory compounds from chicory roots waste after inulin extraction.

Apple concentrate juice industry generates a flavored coproduct (apple aroma) recovered in the evaporation process, which is poorly valuated due to the lack of chemical characterization and standardization. In this study, industry apple aroma was characterized, allowing for the identification of 37 compounds, the majority esters (20), alcohols (7), and aldehydes (4). The storage temperature did not affect its volatile composition. Five key compounds were selected and monitored for 10 months of storage, and also compared with other three productions of another season allowing for observation of the same Aroma Index. Apple pomace was also used to produce a hydrodistillate. Contrary to the apple aroma, apple pomace hydrodistillate was unpleasant, reflected in a different volatile composition. Although no additional aroma fraction could be obtained from this wet byproduct, when dried, apple pomace presented 15 volatile compounds with toasted, caramel, sweet, and green notes. The infusions prepared with the dried apple pomace exhibited 25 volatile compounds with a very pleasant (fruity, apple-like, citrus, and spicy notes) and intense aroma. The addition of sugar changed the volatile profile, providing a less intense flavor, with almond, caramel, and sweet notes. These results show that apple aroma and pomace are high-quality flavoring agents with high potential of valuation as food ingredients.