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Brewer’s spent grain (BSG), the main by-product of the brewing industry, is a rich source of arabinoxylans (AXs) and hydroxycinnamic acids, particularly ferulic acid (FA), which contribute to its prebiotic potential. This study evaluates the prebiotic properties of residual solid from an enzymatically treated BSG, compared to the properties of BSG as a non-enzymatically hydrolyzed control. Although the residual solid exhibited total polyphenol (2581.96 ± 70.63 mg/100 g dry weight) and FA (180.84 ± 3.28 mg/100 g dry weight) contents comparable to those of the non-hydrolyzed control (2500.38 ± 284.20 and 179.59 ± 3.30 mg/100 g dry weight, respectively), the AX content was significantly higher (14,084.81 ± 185.72 mg/100 g), accompanied by a lower degree of feruloylation (12.84 ± 0.23 mg FA/g AX), higher antioxidant activity (64,825.35 ± 4011.24 μmol TE/100 g), and structural changes visualized by scanning electron microscopy. In addition, in vitro colonic fermentation showed a delayed butyrogenic profile, with increased butyrate production compared to the control (3.17 ± 1.44 mM). Microbiota analysis by fluorescence in situ hybridization (FISH) coupled with flow cytometry indicated an increase in butyrate-producing bacteria, including Faecalibacterium prausnitzii (+5.90) and Eubacterium rectale (+6.88). Growth of Bacteroides, Lactobacillus, and Bifidobacterium spp. was also promoted. Overall, these findings suggest that enzymatic processing of BSG can generate a residual solid with modified structural characteristics and potential prebiotic functionality, supporting its potential application as a fermentable flour ingredient in functional foods.

This study aimed to investigate the molecular pathways involved in muscle wasting in an animal model of osteoarthritis (OA) induced by anterior cruciate ligament transection (ACLT) in rats. Reduction of protein syntheses, increased proteolysis and impaired muscle regeneration are important pathways related to muscle wasting, and myogenin, MyoD, myostatin and MuRF-1 are some of their markers. Female Wistar rats were allocated into two groups: OA (submitted to the ACLT) and SHAM (submitted to surgery without ACLT). Nociception, spontaneous exploratory locomotion and body weight of animals were evaluated weekly. Twelve weeks after the disease induction, animals were euthanized, and the right knee joints were collected. Gastrocnemius muscle of the right hind paw were dissected and weighed. Gastrocnemius was used for evaluation of muscle atrophy and expression of IL-1β, TNF-α, Pax7, myogenin, MyoD, myostatin and MuRF-1. Histopathology of the knee confirmed the development of the disease in animals of OA group. Gastrocnemius of OA animals showed a reduction of about 10% in area and an increased IL-1β expression compared to animals of SHAM group. Expression of myostatin was increased in OA group, while myogenin expression was decreased. TNF-α, Pax7, MuRF-1 and MyoD expression was similar in both OA and SHAM groups. Nociception was significantly elevated in OA animals in the last two weeks of experimental period. Spontaneous exploratory locomotion, body weight and weight of gastrocnemius showed no difference between OA and SHAM groups. Gastrocnemius atrophy in OA induced by ACLT involves elevated expression of IL-1β within the muscle, as well as increased expression of myostatin and decreased expression of myogenin. Therefore, muscle wasting may be linked to impaired muscle regeneration.

Background The traditional spoon-feeding approach to introduction of solid foods during the complementary feeding period is supported by consensus in the scientific literature. However, a method called Baby-Led Introduction to SolidS (BLISS) has been proposed as an alternative, allowing infants to self-feed with no adult interference. To date, there have been no trials in the Brazilian population to evaluate the effectiveness of BLISS in comparison to the traditional approach. Methods/design To evaluate and compare three different complementary feeding methods. Data on 144 mother-child pairs will be randomized into intervention groups by methods: (A) strict Parent-Led Weaning; (B) strict Baby-Led Introduction to SolidS; and (C) a mixed method. Prospective participants from Porto Alegre, Brazil, and nearby cities will be recruited through the Internet. The interventions will be performed by nutritionists and speech therapists, at 5.5 months of age of the child, at a private nutrition office equipped with a test kitchen where meals will be prepared according to the randomized method. The pairs will be followed up at 7, 9, and 12 months of age. Data will be collected through questionnaires designed especially for this study, which will include a 24h child food recall, questionnaires on the child’s and parents’ eating behavior, oral habits, eating difficulties, and choking prevalence. At 12 months of age, children will undergo blood collection to measure hemoglobin, ferritin, and C-reactive protein, saliva collection for analysis of genetic polymorphisms, and oral examination. Anthropometric parameters (child and maternal) will be measured at the baseline intervention, at a 9 month home visit, and at the end-of-study visit at the hospital. The primary outcome will be child growth and nutritional status z -scores at 12 months; secondary outcomes will include iron status, feeding behavior, acceptability of the methods, dietary variety, choking, eating behaviors, food preferences, acceptance of bitter and sweet flavors, suction, oral habits, oral hygiene behavior, dental caries, gingival health status, and functional constipation. Discussion The trial intends to ascertain whether there are potential advantages to the BLISS complementary feeding method in this specific population, generating data to support families and healthcare providers. Trial registration Brazilian Clinical Trials Registry (ReBEC): RBR- 229scm number U1111-1226-9516 . Registered on September 24, 2019.

A safe and effective vaccine with long-term protection against SARS-CoV-2 variants of concern (VOCs) is a global health priority. Here, we develop lipid nanoparticles (LNPs) to provide safe and effective delivery of plasmid DNA (pDNA) and show protection against VOCs in female small animal models. Using a library of LNPs encapsulating unique barcoded DNA (b-DNA), we screen for b-DNA delivery after intramuscular administration. The top-performing LNPs are further tested for their capacity of pDNA uptake in antigen-presenting cells in vitro. The lead LNP is used to encapsulate pDNA encoding the HexaPro version of SARS-CoV-2 spike (LNP-HPS) and immunogenicity and protection is tested in vivo. LNP-HPS elicit a robust protective effect against SARS-CoV-2 Gamma (P.1), correlating with reduced lethality, decreased viral load in the lungs and reduced lung damage. LNP-HPS induce potent humoral and T cell responses against P.1, and generate high levels of neutralizing antibodies against P.1 and Omicron (B.1.1.529). Our findings indicate that the protective efficacy and immunogenicity elicited by LNP-HPS are comparable to those achieved by the approved COVID-19 vaccine from Biontech/Pfizer in animal models. Together, these findings suggest that LNP-HPS hold great promise as a vaccine candidate against VOCs. Here the authors screen different lipid nanoparticle (LNP) formulations for intramuscular delivery of plasmid DNA and uptake by antigen-presenting cells. The lead LNP exhibits immunogenicity and protection in small animal models that is comparable to approved SARS-CoV-2 mRNA vaccine formulations.

Background/Objectives: For the development of new treatments, the acute phase of Chagas disease (CD) in experimental models acts as a filter to screen out potentially effective interventions. Therefore, the aim of this study was to evaluate ZnO nanocrystals and Ag-ZnO/AgO nanocomposites containing different proportions of silver (ZnO:5Ag, ZnO:9Ag and ZnO:11Ag) in an experimental model of the acute phase of CD. Methods: C57Bl/6 mice were infected with 1000 forms of the Colombian strain of T. cruzi. The treatment was carried out by gavage with 5 mg/kg/d for 7 consecutive days from the first detection of parasitemia. Weight, parasitemia and survival were assessed during treatment and up to the day of euthanasia. After euthanasia, the cardiac and intestinal parasitism, inflammatory infiltrate, collagen deposition and cytokine dosages were analyzed. Results: It was observed that the nanocomposites ZnO:9Ag and ZnO:11Ag were the most effective in reducing parasitemia and increasing the survival of the infected animals. However, pure ZnO induced the maintenance of parasitemia and reduced their survival. The ZnO:9Ag and ZnO:11Ag nanocomposites were able to reduce the number of cardiac amastigote nests. In addition, they were responsible for reducing TNF-α and IL-6 in situ. ZnO:9Ag and ZnO:11Ag induced a reduction in the intestinal inflammatory infiltrate and neuronal protection in the myenteric plexus, as well as reducing TNF-α in situ. Conclusions: Based on these results, it is suggested that there is an ideal concentration in terms of the proportion of Ag/AgO and ZnO in nanocomposites for use against CD. Thus, ZnO:9Ag or ZnO:11Ag nanomaterials are potential candidates for the development of new biotechnological products for the therapy of CD.

Background and Aims. Sepsis is defined as a life-threatening organ dysfunction due to a dysregulated host immune response to an infection. Curcumin is a yellow polyphenol derived from the rhizome of Curcuma longa with anti-inflammatory and antioxidant properties scientifically proven, a condition that allowed its use as a tool in the treatment of sepsis. Thus, the purpose of this article was to systematically review the evidence on the impact of curcumin’s anti-inflammatory effect on experimental sepsis. Methods. For this, the PubMed, MEDLINE, EMBASE, Scopus, Web of Science, and LILACS databases were used, and the research was not limited to a specific publication period. Only original articles in English using in vivo experimental models (rats or mice) of sepsis induction performed by administration of lipopolysaccharide (LPS) or cecal ligation and perforation surgery (CLP) were included in the study. Studies using curcumin in dry extract or with a high degree of purity were included. At initial screening, 546 articles were selected, and of these, 223 were eligible for primary evaluation. Finally, 12 articles with full text met all inclusion criteria. Our results showed that curcumin may inhibit sepsis-induced complications such as brain, heart, liver, lungs, and kidney damage. Curcumin can inhibit inflammatory factors, prevent oxidative stress, and regulate immune responses in sepsis. Additionally, curcumin increased significantly the survival rates after experimental sepsis in several studies. The modulation of the immune response and mortality by curcumin reinforces its protective effect on sepsis and indicates a potential therapeutic tool for the treatment of sepsis.

Chagas disease (CD), caused by Trypanosoma cruzi , leads to cardiomyopathy in approximately 20–30% of infected individuals. Interleukin-11 (IL-11) has been implicated in cardiac fibrosis, although its immunological role in this context remains unclear. This study investigated the temporal dynamics of IL-11 and its receptor, IL-11Rα, expression in the hearts of C57BL/6 mice infected with 1,000 trypomastigote forms of the Y or Colombian strains of T. cruzi . Mice were euthanized at 5, 15, 30, 60, and 120 days post-infection (dpi). Survival, parasitemia, and body and heart weights were monitored. Cardiac tissue was analyzed for parasite nests, myocarditis, collagen deposition, and expression of the IL-11 receptor alpha (IL-11Rα). Cytokine profiles were evaluated by ELISA and Cytometric Bead Array. Histopathological analysis revealed more intense myocarditis, parasite load, and collagen deposition in mice infected with the Colombian strain. Both strains induced IFN-γ, TNF-α, and IL-6 in cardiac tissue; however, IL-10, IL-4, and IL-17 were detected only in the Y strain, indicating a more balanced immune response. Despite the absence of significant IL-11 upregulation in either infection, IL-11Rα expression was progressively increased over time and positively correlated with collagen deposition. These findings suggest that IL-11Rα may play a role in cardiac remodeling and fibrosis independently of IL-11 upregulation. The results reinforce the importance of T. cruzi strain variability in disease outcome and highlight the IL-11/IL-11Rα axis as a potential target for further investigation in Chagas cardiomyopathy. Graphical Abstract The kinetics of IL-11 and IL-11Rα expression in the heart during experimental Trypanosoma cruzi infection reveal striking differences between the Y and Colombian strains over time (5, 15, 30, 60, and 120 days post-infection). The shaded areas in green and orange represent IL-11Rα expression and IL-11 production, respectively. In the Y strain, IL-11 production is detectable throughout the infection, peaking around 30 days. In contrast, the Colombian strain exhibits lower IL-11 expression. IL-11Rα expression is upregulated in both strains: starting at 15 dpi in the Y strain and at 60 dpi in the Colombian strain, remaining elevated until 120 dpi. The colored lines indicate the kinetics of other parameters: Pro-inflammatory cytokines (TNF-α, IFN-γ, IL-6): red; Regulatory/Th2/Th17 cytokines (IL-10, IL-4, IL-17): green; Cardiac parasitism ( T. cruzi nests): purple; Inflammatory infiltrate: black; Collagen deposition: brown. The distinct peaks observed between groups reflect the specific immunopathological characteristics of each strain in terms of inflammation, immune response, and cardiac damage. This graphic scheme provides an integrated summary of the dynamics between the analyzed parameters throughout the course of infection.

Zinc oxide nanoparticles (ZnO NPs) are metal oxide nanomaterials, which are important for several applications: antibacterial, anthelmintic, antiprotozoal and antitumoral, among others. These applications are mainly related to the ability to spontaneously produce and induce the production of reactive oxygen species that are important components for the destruction of pathogens and tumor cells. While trying to potentiate ZnO NPs, studies have associated these NPs with silver oxide (AgO) or silver (Ag) NPs. It has already been reported that this combination (Ag-ZnO/AgO NPs) is able to enhance the microbicidal potential. Although possessing much potential for several purposes, it is important to evaluate whether this association also poses the risk of toxicity to cells and experimental models. Therefore, this work aimed to evaluate the toxicity of various Ag-ZnO/AgO NP nanocomposites, in vitro and in vivo. Accordingly, ZnO nanocrystals and nanocomposites with various concentrations of AgO (ZnO:5Ag, ZnO:9Ag or ZnO:11Ag) were used in different cytotoxicity models: Galleria mellonella (G. mellonella), cell lines (VERO and RAW 264.7) and C57BL/6 mice. In the G. mellonella model, four concentrations were used in a single dose, with subsequent evaluation of mortality. In the case of cells, serial concentrations starting at 125 µg/mL were used, with subsequent cytotoxicity assessment. Based on the safe doses obtained in G. mellonella and cell models, the best doses were used in mice, with subsequent evaluations of weight, biochemistry as also renal and liver histopathology. It was observed that the toxicity, although low, of the nanocomposites was dependent upon the concentration of AgO used in association with ZnO NPs, both in vitro and in vivo.

Immunotherapy has revolutionized cancer treatment by harnessing the immune system to enhance antitumor responses while minimizing off-target effects. Among the promising cancer-specific therapies, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has attracted significant attention. Here, we developed an ionizable lipid nanoparticle (LNP) platform to deliver TRAIL mRNA (LNP-TRAIL) directly to the tumor microenvironment (TME) to induce tumor cell death. Our LNP-TRAIL was formulated via microfluidic mixing and the induction of tumor cell death was assessed in vitro. Next, we investigated the ability of LNP-TRAIL to inhibit colon cancer progression in vivo in combination with a TME normalization approach using Losartan (Los) or angiotensin 1-7 (Ang(1-7)) to reduce vascular compression and deposition of extracellular matrix in mice. Our results demonstrated that LNP-TRAIL induced tumor cell death in vitro and effectively inhibited colon cancer progression in vivo, particularly when combined with TME normalization induced by treatment Los or Ang(1-7). In addition, potent tumor cell death as well as enhanced apoptosis and necrosis was found in the tumor tissue of a group treated with LNP-TRAIL combined with TME normalization. Together, our data demonstrate the potential of the LNP to deliver TRAIL mRNA to the TME and to induce tumor cell death, especially when combined with TME normalization. Therefore, these findings provide important insights for the development of novel therapeutic strategies for the immunotherapy of solid tumors.

The objective of this study was to evaluate the ruminal parameters (pH, N-NH3, and microbial protein) and morphometry of the rumen and intestine of sheep fed with a diet containing four different levels of the spineless cactus variety, Baiana. The experiment was conducted at the National Semi-Arid Institute in Campina Grande, PB, Brazil. A total of 40 male sheep submitted to the confinement regime were used in a completely randomized design with four treatments (0, 15, 30, and 45% dry matter basis) and ten replicates, with an initial body weight of 23.7 ± 3.08 kg. Experimental diets were composed of ground corn, soybean meal, urea, mineral supplement, limestone, Tifton 85 hay, and spineless cactus of the Baiana variety. The pH, ammonia nitrogen, and microbial protein were evaluated in the ruminal fluid, alongside the morphometric characteristics of the rumen and intestine. While the addition of the spineless cactus did not affect N-NH3, it caused a linear reduction in the ruminal pH following 4 h of feeding, and also increased the microbial protein. In addition, it stimulated a reduction in the height of the papillae and the muscle layer of the rumen, and induced the mucosal height in the intestine to increase. The addition of up to 30% of spineless cactus in the diet of sheep without a defined breed did not alter the N-NH3, pH, and ruminal histology, but it did increase the production of microbial protein and intestinal mucosa.