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Background/Objective: Autoimmune thyroid diseases (AITD) affect 2 to 5% of the general population. This study aimed to determine changes in activity of A-Tg and A-TPO antibodies before, during, and after pregnancy in women with previous AITD. Methods: This was a single-center study with a retrospective review of the medical records of 30 female patients aged 25-41 years who came to our endocrinology service in the city of Santo André, state of São Paulo, Brazil, to investigate thyroid diseases. The following data were reviewed: total triiodothyronine (totalT3), total thyroxine (totalT4), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and anti-TSH receptor antibodies (anti-TSH receptor or anti-thyrotropin receptor antibodies (TRAb), anti-thyroid peroxidase (A-TPO), and anti-thyroglobulin (A-Tg)). These data were reviewed for 30 patients before and during the three trimesters of pregnancy and during the three months after pregnancy. Results: During gestation, we observed a progressive decrease in the blood values of A-TPO and A-Tg, which reached their lowest values in the third trimester of pregnancy, but after birth, they returned to values statistically equivalent to those before pregnancy. Analyzing the three trimesters and the post-pregnancy period, A-TPO increased 192% between the first trimester and postpartum (p = 0.009); it increased 627% between the second trimester and postpartum (p < 0.001); and it increased >1000% between the third trimester and postpartum (p < 0.001). There was no significant difference in the A-TPO values between the pre- and post-gestational periods (p = 1.00), between the first and second trimesters (p = 0.080), or between the second and third trimesters (p = 0.247). Conclusions: According to the results presented here, we observed changes in the activities of A-Tg and A-TPO antibodies during and after pregnancy in women with previous AITD. In women who intend to become pregnant, are pregnant, or have given birth within three months, it is essential to monitor A-TPO, A-Tg, and thyroid function as well as serum thyroid hormones and TSH to identify thyroid dysfunction in a timely manner and adjust the treatment strategy to avoid the deleterious effects of hypothyroidism on both mother and baby during and after pregnancy.
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Lactobacillus delbrueckii CIDCA 133 is a promising health-promoting bacterium shown to alleviate intestinal inflammation. However, the specific bacterial components responsible for these effects remain largely unknown. Here, we demonstrated that consuming extractable proteins from the CIDCA 133 strain effectively relieved acute ulcerative colitis in mice. This postbiotic protein fraction reduced the disease activity index and prevented colon shortening in mice. Furthermore, histological analysis revealed colitis prevention with reduced inflammatory cell infiltration into the colon mucosa. Postbiotic consumption also induced an immunomodulatory profile in colitic mice, as evidenced by both mRNA transcript levels (Tlr2, Nfkb1, Nlpr3, Tnf, and Il6) and cytokines concentration (IL1ß, TGFß, and IL10). Additionally, it enhanced the levels of secretory IgA, upregulated the transcript levels of tight junction proteins (Hp and F11r), and improved paracellular intestinal permeability. More interestingly, the consumption of postbiotic proteins modulated the gut microbiota (Bacteroides, Arkkemansia, Dorea, and Oscillospira). Pearson correlation analysis indicated that IL10 and IL1ß levels were positively associated with Bacteroides and Arkkemansia_Lactobacillus abundance. Our study reveals that CIDCA 133-derived proteins possess anti-inflammatory properties in colonic inflammation.
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STATEMENT OF PROBLEM: Prefabricated and custom glass fiber posts have been successfully used to reconstruct endodontically treated teeth. However, the performance of computer-aided design and computer-aided manufacture (CAD-CAM) milled glass fiber posts is unclear. PURPOSE: The purpose of this systematic review with meta-analysis was to compare the fracture and bond strength and cement layer thickness of CAD-CAM milled glass fiber posts with prefabricated or custom glass fiber posts. MATERIAL AND METHODS: The protocol was registered in the Open Science Framework (http://osf.io/65jm7). Two reviewers searched the PubMed/MEDLINE, Web of Science, Embase, Scopus, and ProQuest databases for articles up to September 2023. In addition, the reference lists were hand searched. A meta-analysis was performed by using the RevMan 5.4 program. The risk of bias was assessed using the RoBDEMAT tool. RESULTS: After screening, a total of 18 studies were included. The CAD-CAM milled glass fiber posts showed higher fracture strength (P=.02; Standardized Mean Difference [SMD]: 0.57; 95% Confidence Interval [CI]: 0.07 to 1.07), bond strength (P=.010; SMD: 1.07; 95% CI: 0.26 to 1.89), and lower cement layer thickness (P=.009; SMD: -2.94; 95% CI: -5.15 to -0.73) when compared with prefabricated glass fiber posts. However, fracture strength (P=.53; SMD: 0.38; 95% CI: -0.79 to 1.54) and bond strength (P=.90; SMD: -0.05; 95% CI: -0.81 to 0.72) were statistically similar between CAD-CAM milled and custom glass fiber posts. Significant and substantial heterogeneity was observed in all meta-analyzes (P<.01; I>60%). The studies sufficiently reported most domains related to bias, except for randomization of samples, sample size rationale and reporting and operator blinding. CONCLUSIONS: CAD-CAM milled and custom glass fiber posts provide an effective and safe option for restoring endodontically treated teeth, especially for weakened teeth or enlarged root canals. However, further well-designed clinical research is recommended to strengthen these findings.
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Dimethyl fumarate (DMF, Tecfidera) is an oral drug utilized to treat relapsing-remitting multiple sclerosis (MS). DMF treatment reduces disease activity in MS. Gastrointestinal discomfort is a common adverse effect of the treatment with DMF. This study aimed to investigate the effect of DMF administration in the gut draining lymph nodes cells of C57BL6/J female mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We have demonstrated that the treatment with DMF (7.5 mg/kg) significantly reduces the severity of EAE. This reduction of the severity is accompanied by the increase of both proinflammatory and anti-inflammatory mechanisms at the beginning of the treatment. As the treatment progressed, we observed an increasing number of regulatory Foxp3 negative CD4 T cells (Tr1), and anti-inflammatory cytokines such as IL-27, as well as the reduction of PGE2 level in the mesenteric lymph nodes of mice with EAE. We provide evidence that DMF induces a gradual anti-inflammatory response in the gut draining lymph nodes, which might contribute to the reduction of both intestinal discomfort and the inflammatory response of EAE. These findings indicate that the gut is the first microenvironment of action of DMF, which may contribute to its effects of reducing disease severity in MS patients.
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Dimetilfumarato , Encefalomielitis Autoinmune Experimental , Ganglios Linfáticos , Ratones Endogámicos C57BL , Linfocitos T Reguladores , Animales , Dimetilfumarato/farmacología , Dimetilfumarato/uso terapéutico , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/inmunología , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/efectos de los fármacos , Ratones , Femenino , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/efectos de los fármacos , Mesenterio , Citocinas/metabolismo , Inmunosupresores/farmacología , Inmunosupresores/uso terapéutico , Modelos Animales de EnfermedadRESUMEN
Lactobacillus delbrueckii subsp. lactis CIDCA 133 is a health-promoting bacterium that can alleviate gut inflammation and improve the epithelial barrier in a mouse model of mucositis. Despite these beneficial effects, the protective potential of this strain in other inflammation models, such as inflammatory bowel disease, remains unexplored. Herein, we examined for the first time the efficacy of Lactobacillus delbrueckii CIDCA 133 incorporated into a fermented milk formulation in the recovery of inflammation, epithelial damage, and restoration of gut microbiota in mice with dextran sulfate sodium-induced colitis. Oral administration of Lactobacillus delbrueckii CIDCA 133 fermented milk relieved colitis by decreasing levels of inflammatory factors (myeloperoxidase, N-acetyl-ß-D-glucosaminidase, toll-like receptor 2, nuclear factor-κB, interleukins 10 and 6, and tumor necrosis factor), secretory immunoglobulin A levels, and intestinal paracellular permeability. This immunobiotic also modulated the expression of tight junction proteins (zonulin and occludin) and the activation of short-chain fatty acids-related receptors (G-protein coupled receptors 43 and 109A). Colonic protection was effectively associated with acetate production and restoration of gut microbiota composition. Treatment with Lactobacillus delbrueckii CIDCA 133 fermented milk increased the abundance of Firmicutes members (Lactobacillus genus) while decreasing the abundance of Proteobacteria (Helicobacter genus) and Bacteroidetes members (Bacteroides genus). These promising outcomes influenced the mice's mucosal healing, colon length, body weight, and disease activity index, demonstrating that this immunobiotic could be explored as an alternative approach for managing inflammatory bowel disease.
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Colitis , Productos Lácteos Cultivados , Sulfato de Dextran , Microbioma Gastrointestinal , Lactobacillus delbrueckii , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Colitis/microbiología , Colitis/inducido químicamente , Colitis/metabolismo , Colitis/tratamiento farmacológico , Lactobacillus delbrueckii/metabolismo , Productos Lácteos Cultivados/microbiología , Ratones , Probióticos/uso terapéutico , Masculino , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Mucosa Intestinal/microbiología , Mucosa Intestinal/metabolismo , Inflamación , Colon/microbiología , Colon/metabolismo , LactobacillusRESUMEN
The poultry industry faces significant challenges in controlling Salmonella contamination while reducing antibiotic use, particularly with the emergence of Salmonella Heidelberg (SH) strains posing risks to food safety and public health. Probiotics, notably lactic acid bacteria (LAB) and Saccharomyces boulardii (SB) offer promising alternatives for mitigating Salmonella colonization in broilers. Understanding the efficacy of probiotics in combating SH and their impact on gut health and metabolism is crucial for improving poultry production practices and ensuring food safety standards. This study aimed to assess the inhibitory effects of LAB and SB against SH both in vitro and in vivo broilers, while also investigating their impact on fecal metabolites and caecal microbiome composition. In vitro analysis demonstrated strong inhibition of SH by certain probiotic strains, such as Lactiplantibacillus plantarum (LP) and Lacticaseibacillus acidophilus (LA), while others like SB and Lactobacillus delbrueckii (LD) did not exhibit significant inhibition. In vivo testing revealed that broilers receiving probiotics had significantly lower SH concentrations in cecal content compared to the positive control (PC) at all ages, indicating a protective effect of probiotics against SH colonization. Metagenomic analysis of cecal-content microbiota identified predominant bacterial families and genera, highlighting changes in microbiota composition with age and probiotic supplementation. Additionally, fecal metabolomics profiling showed alterations in metabolite concentrations, suggesting reduced oxidative stress, intestinal inflammation, and improved gut health in probiotic-supplemented birds. These findings underscore the potential of probiotics to mitigate SH colonization and improve broiler health while reducing reliance on antibiotics.
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Pollos , Microbioma Gastrointestinal , Enfermedades de las Aves de Corral , Probióticos , Saccharomyces boulardii , Salmonelosis Animal , Animales , Pollos/fisiología , Probióticos/farmacología , Probióticos/administración & dosificación , Enfermedades de las Aves de Corral/prevención & control , Enfermedades de las Aves de Corral/microbiología , Salmonelosis Animal/prevención & control , Salmonelosis Animal/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Saccharomyces boulardii/fisiología , Salmonella enterica/fisiología , Alimentación Animal/análisis , Lactobacillales/fisiología , Heces/microbiología , Heces/química , Dieta/veterinaria , MasculinoRESUMEN
Introduction and objective: p62 is a human multifunctional adaptor protein involved in key cellular processes such as tissue homeostasis, inflammation, and cancer. It acts as a negative regulator of inflammasome complexes. It may thus be considered a good candidate for therapeutic use in inflammatory bowel diseases (IBD), such as colitis. Probiotics, including recombinant probiotic strains producing or delivering therapeutic biomolecules to the host mucosal surfaces, could help prevent and mitigate chronic intestinal inflammation. The objective of the present study was to combine the intrinsic immunomodulatory properties of the probiotic Lactococcus lactis NCDO2118 with its ability to deliver health-promoting molecules to enhance its protective and preventive effects in the context of ulcerative colitis (UC). Material and methods: This study was realized in vivo in which mice were supplemented with the recombinant strain. The intestinal barrier function was analyzed by monitoring permeability, secretory IgA total levels, mucin expression, and tight junction genes. Its integrity was evaluated by histological analyses. Regarding inflammation, colonic cytokine levels, myeloperoxidase (MPO), and expression of key genes were monitored. The intestinal microbiota composition was investigated using 16S rRNA Gene Sequencing. Results and discussion: No protective effect of L. lactis NCDO2118 pExu:p62 was observed regarding mice clinical parameters compared to the L. lactis NCDO2118 pExu: empty. However, the recombinant strain, expressing p62, increased the goblet cell counts, upregulated Muc2 gene expression in the colon, and downregulated pro-inflammatory cytokines Tnf and Ifng when compared to L. lactis NCDO2118 pExu: empty and inflamed groups. This recombinant strain also decreased colonic MPO activity. No difference in the intestinal microbiota was observed between all treatments. Altogether, our results show that recombinant L. lactis NCDO2118 delivering p62 protein protected the intestinal mucosa and mitigated inflammatory damages caused by dextran sodium sulfate (DSS). We thus suggest that p62 may constitute part of a therapeutic approach targeting inflammation.
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Multi-strain Limosilactobacillus (L.) fermentum is a potential probiotic with reported immunomodulatory properties. This study aimed to evaluate the composition, richness, and diversity of the gut microbiota in male and female rats after treatment with a multi-strain of L. fermentum at different doses. Thirty rats (fifteen male and fifteen female) were allocated into a control group (CTL), a group receiving L. fermentum at a dose of 108 CFU (Lf-108), and a group receiving L. fermentum at a dose of 1010 CFU (Lf-1010) for 13 weeks. Gut microbiota and serum cytokine levels were evaluated after L. fermentum treatment. Male CTL rats had a lower relative abundance of Bifidobacteriaceae and Prevotella and a lower alpha diversity than their female CTL counterparts (p < 0.05). In addition, male CTL rats had a higher Firmicutes/Bacteroidetes (F/B) ratio than female CTL rats (p < 0.05). In female rats, the administration of L. fermentum at 108 CFU decreased the relative abundance of Bifidobacteriaceae and Anaerobiospirillum and increased Lactobacillus (p < 0.05). In male rats, the administration of L. fermentum at 1010 CFU decreased the F/B ratio and increased Lachnospiraceae and the diversity of the gut microbiota (p < 0.05). The relative abundance of Lachnospiraceae and the alpha-diversity of gut microbiota were negatively correlated with serum levels of IL1ß (r = -0.44) and TNFα (r = -0.39), respectively. This study identified important changes in gut microbiota between male and female rats and showed that a lower dose of L. fermentum may have more beneficial effects on gut microbiota in females, while a higher dose may result in more beneficial effects on gut microbiota in male rats.
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The present study aimed to investigate the contextual inequalities of specialized public dental care (SPDC) in Brazil. The outcome was the trajectory of dental specialized production in municipalities with SPDC (from 2015 to 2017) obtained by group-based trajectory modeling. A Poisson regression model was used to analyze the factors associated with the high trajectory of SPDC production. The inequality indicators for SPDC production were the slope index and the concentration index according to contextual factors. The study included 954 SPDC units distributed across 893 municipalities. Among the municipalities evaluated, 62.9% had a low trajectory of SPDC. Large-sized municipalities had the highest production (IRR = 2.84, 95%CI: 1.94-4.14) and the southern region had the lowest production (IRR = 0.73, 95%CI: 0.58-0.92). Municipalities presenting a very high human development index (HDI) showed the greatest SPDC production (IRR = 3.34, 95%CI: 1.09-10.24), as well as municipalities with the highest tertile of schooling rate (IRR = 1.23, 95%CI: 1.00-1.50). The absolute inequality was 52.1 percentage points for the average monthly wage (p < 0.001), 61.0 percentage points for the HDI (p < 0.001), -22.1 for infant mortality rate (p <0.001), and 14.8 for the schooling rate (p = 0.012). Thus, there are contextual inequalities in the Brazilian SPDC. Higher scores for social indicators were associated with better SPDC performance.
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Encuestas de Salud Bucal , Salud Pública , Humanos , Factores Socioeconómicos , Brasil , Ciudades , Atención OdontológicaRESUMEN
OBJECTIVE: This observational study aimed to explore the metagenomics of subgingival biofilms in individuals with varying degrees of asthma, from severe to none, to elucidate the association between the subgingival microbiome and asthma. MATERIALS AND METHODS: Subgingival biofilm samples were collected from thirty participants at the Asthma Control Program Outpatient Clinic in Bahia (ProAR). These samples were categorized into six groups based on the severity of asthma and the presence or absence of periodontitis. We employed next-generation sequencing (Illumina MiSeq), targeting the 16S rRNA gene, to characterize the microbial communities present. Our analysis included descriptive statistics and sequencing data, evaluated using multivariate statistical methods such as the Shannon index, principal coordinate analysis, and the Bray-Curtis dissimilarity. RESULTS: Our findings indicate a higher prevalence of periodontally detrimental bacterial genera in individuals with severe asthma and periodontitis. Additionally, individuals with asthma, but without periodontitis, exhibited a tendency toward dysbiosis, particularly in cases of severe asthma. CONCLUSION: This research provides new insights into the composition of the subgingival microbiome in individuals with varying severities of asthma and periodontitis. The genera identified in this study underscore the need for further investigations to build upon these findings.
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RESEARCH HIGHLIGHTS: Peptides + CpG-ODN reduced SH in caeca at the first week post-infection.Administered formulations did not reduce SH-faecal excretion.Levels of intestinal IgA were similar between all groups.CpG-ODN improved some parameters associated with chick intestinal health.
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Enfermedades de las Aves de Corral , Salmonelosis Animal , Salmonella enterica , Animales , Serogrupo , Salmonelosis Animal/prevención & control , Salmonelosis Animal/microbiología , Enfermedades de las Aves de Corral/prevención & control , Enfermedades de las Aves de Corral/microbiología , PollosRESUMEN
Clostridioides difficile infection (CDI) poses a significant global health threat owing to its substantial morbidity and associated healthcare costs. A key challenge in controlling CDI is the risk of multiple recurrences, which can affect up to 30% of patients. In such instances, fecal microbiota transplantation (FMT) is increasingly recognized as the optimal treatment. However, few related studies have been conducted in developing countries, and the microbiota composition of Brazilian patients and its dynamic modification post-FMT remain largely unexplored. This study aimed to evaluate the changes in the bacterial gut microbiome in Brazilian patients with recurrent CDI post-FMT. Ten patients underwent FMT, and the primary and overall CDI resolution rates were 80% and 90% after the first and second FMT, respectively. FMT was associated with an early increase in Shannon's diversity, evident as soon as 1 week post-FMT and persisting for at least 25 days post-treatment. Post-treatment, the abundance of Firmicutes increased and that of Proteobacteria decreased. Specifically, the abundance of the genera Ruminococcus, Faecalibacterium, Lachnospira, and Roseburia of the Firmicutes phylum was significantly higher 1 week post-transplantation, with Ruminococcus and Faecalibacterium remaining enriched 25 days post-transplantation. This study is the first of its kind in Brazil to evaluate the microbiota of a donor and patients undergoing FMT. Our findings suggest that FMT can induce remarkable changes in the gut microbiota, characterized by an early and sustained increase in diversity lasting at least 25 days. FMT also promotes enrichment of genera such as Ruminococcus spp., Faecalibacterium spp., and Roseburia spp., essential for therapeutic success.
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Clostridioides difficile , Infecciones por Clostridium , Microbiota , Humanos , Trasplante de Microbiota Fecal , Brasil , Heces/microbiología , Resultado del Tratamiento , Infecciones por Clostridium/microbiología , BacteriasRESUMEN
Aim: Venous blood derivatives (VBDs) have been suggested as substitutes for Fetal Bovine Serum (FBS) to improve the clinical transition of cell-based therapies. The literature is not clear about which is the best VBDs substitute. The present study aimed to evaluate the influence of VBDs on cell viability and describe a new method to seed these cells in a 3D Platelet-Rich Fibrin (PRF). Methods: Blood was processed to obtain Platelet-Poor Plasma from PRF (P-PRF), Human Serum (HS), Platelet-Poor Plasma from PRP (P-PRP), activated-PRP (a-PRP), and Platelet lysate (PL). Cells were supplemented with each VBD at 10% and FBS at 10% was the control. Cell viability (fibroblast 3T3/NIH) test was evaluated with MTT assay in two ways: i) cell-seeded and expanded with VBD; ii) cell-seed with FBS and expanded with VBD. To seed the Fibrin construct, cells were suspended in PBS and dropped into the blood sample before performing Choukroun's protocol for PRF. Constructs were cultured for 7 days in VBD supplements and FBS. Histological and Immunohistochemical analysis with vimentin was performed. Cell viability was analyzed by one-way ANOVA. Results: VBD's production time was very heterogeneous. Cells expanded in HS and a-PRP has grown faster. VBD-supplemented culture media provided cell culture highly sensible to trypsin/EDTA 0.25%. Cells seeded and expanded with VBD presented viability comparable to FBS in HS, a-PRP, and P-PRP (p>0.05) and lower in P-PRF and PL groups (p<0.05). The viability of cell seed with FBS and expanded with VBD was similar between P-PRF, a-PRP, PL, and FBS (p>0.05) and lower in HS and P-PRP (p<0.005). PRF-seeded cells showed a positive expression of vimentin and were able to maintain all cells supplemented with VBD. Conclusion: VBD supplements were able to maintain fibroblast cells in 2D and 3D cultures. The new method of the fibrin-cell construct was efficient to insert the cells into the fibrin network
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Sangre , Plaquetas , Albúmina Sérica Bovina , Fibrina , Células , Fibroblastos , Fibrina Rica en PlaquetasRESUMEN
Abstract The present study aimed to investigate the contextual inequalities of specialized public dental care (SPDC) in Brazil. The outcome was the trajectory of dental specialized production in municipalities with SPDC (from 2015 to 2017) obtained by group-based trajectory modeling. A Poisson regression model was used to analyze the factors associated with the high trajectory of SPDC production. The inequality indicators for SPDC production were the slope index and the concentration index according to contextual factors. The study included 954 SPDC units distributed across 893 municipalities. Among the municipalities evaluated, 62.9% had a low trajectory of SPDC. Large-sized municipalities had the highest production (IRR = 2.84, 95%CI: 1.94-4.14) and the southern region had the lowest production (IRR = 0.73, 95%CI: 0.58-0.92). Municipalities presenting a very high human development index (HDI) showed the greatest SPDC production (IRR = 3.34, 95%CI: 1.09-10.24), as well as municipalities with the highest tertile of schooling rate (IRR = 1.23, 95%CI: 1.00-1.50). The absolute inequality was 52.1 percentage points for the average monthly wage (p < 0.001), 61.0 percentage points for the HDI (p < 0.001), -22.1 for infant mortality rate (p <0.001), and 14.8 for the schooling rate (p = 0.012). Thus, there are contextual inequalities in the Brazilian SPDC. Higher scores for social indicators were associated with better SPDC performance.
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BACKGROUND: Probiotics have gained attention for their potential maintaining gut and immune homeostasis. They have been found to confer protection against pathogen colonization, possess immunomodulatory effects, enhance gut barrier functionality, and mitigate inflammation. However, a thorough understanding of the unique mechanisms of effects triggered by individual strains is necessary to optimize their therapeutic efficacy. Probiogenomics, involving high-throughput techniques, can help identify uncharacterized strains and aid in the rational selection of new probiotics. This study evaluates the potential of the Escherichia coli CEC15 strain as a probiotic through in silico, in vitro, and in vivo analyses, comparing it to the well-known probiotic reference E. coli Nissle 1917. Genomic analysis was conducted to identify traits with potential beneficial activity and to assess the safety of each strain (genomic islands, bacteriocin production, antibiotic resistance, production of proteins involved in host homeostasis, and proteins with adhesive properties). In vitro studies assessed survival in gastrointestinal simulated conditions and adhesion to cultured human intestinal cells. Safety was evaluated in BALB/c mice, monitoring the impact of E. coli consumption on clinical signs, intestinal architecture, intestinal permeability, and fecal microbiota. Additionally, the protective effects of both strains were assessed in a murine model of 5-FU-induced mucositis. RESULTS: CEC15 mitigates inflammation, reinforces intestinal barrier, and modulates intestinal microbiota. In silico analysis revealed fewer pathogenicity-related traits in CEC15, when compared to Nissle 1917, with fewer toxin-associated genes and no gene suggesting the production of colibactin (a genotoxic agent). Most predicted antibiotic-resistance genes were neither associated with actual resistance, nor with transposable elements. The genome of CEC15 strain encodes proteins related to stress tolerance and to adhesion, in line with its better survival during digestion and higher adhesion to intestinal cells, when compared to Nissle 1917. Moreover, CEC15 exhibited beneficial effects on mice and their intestinal microbiota, both in healthy animals and against 5FU-induced intestinal mucositis. CONCLUSIONS: These findings suggest that the CEC15 strain holds promise as a probiotic, as it could modulate the intestinal microbiota, providing immunomodulatory and anti-inflammatory effects, and reinforcing the intestinal barrier. These findings may have implications for the treatment of gastrointestinal disorders, particularly some forms of diarrhea.
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Proteínas de Escherichia coli , Mucositis , Probióticos , Ratones , Humanos , Animales , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Inflamación , Probióticos/uso terapéuticoRESUMEN
Bacteria of the Leuconostoc genus are Gram-positive bacteria that are commonly found in raw milk and persist in fermented dairy products and plant food. Studies have already explored the probiotic potential of L. mesenteroides, but not from a probiogenomic perspective, which aims to explore the molecular features responsible for their phenotypes. In the present work, probiogenomic approaches were applied in strains F-21 and F-22 of L. mesenteroides isolated from human milk to assess their biosafety at the molecular level and to correlate molecular features with their potential probiotic characteristics. The complete genome of strain F-22 is 1.99 Mb and presents one plasmid, while the draft genome of strain F-21 is 1.89 Mb and presents four plasmids. A high percentage of average nucleotide identity among other genomes of L. mesenteroides (≥ 96%) corroborated the previous taxonomic classification of these isolates. Genomic regions that influence the probiotic properties were identified and annotated. Both strains exhibited wide genome plasticity, cell adhesion ability, proteolytic activity, proinflammatory and immunomodulation capacity through interaction with TLR-NF-κB and TLR-MAPK pathway components, and no antimicrobial resistance, denoting their potential to be candidate probiotics. Further, the strains showed bacteriocin production potential and the presence of acid, thermal, osmotic, and bile salt resistance genes, indicating their ability to survive under gastrointestinal stress. Taken together, our results suggest that L. mesenteroides F-21 and F-22 are promising candidates for probiotics in the food and pharmaceutical industries.
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Introduction: The medial preoptic area (mPOA) participates in thermoregulatory control and blood pressure modulation as shown by studies with electrical stimulation of this area or cobalt chloride injection, a non-selective synapse inhibitor. This study aimed to investigate whether angiotensin II (Ang II) and GABA could act or not in the mPOA to mediate the cardiovascular and micturition control pathways. Methods: Female Wistar rats were submitted to stereotaxic surgery for implantation of a guide cannula into the mPOA 7 days prior to the experiments. Afterwards, the animals were isoflurane- anesthetized and submitted to the catheterization of the femoral artery and vein and urinary bladder cannulation for mean arterial pressure (MAP), heart rate (HR), and intravesical pressure (IP) recordings, respectively. After the baseline MAP, HR, and IP recordings for 15 min, Ang II (0.1 nM, 1 µL), losartan (AT-1 receptor antagonist, 100 nM, 1 µL), GABA (50 mM, 1 µL) or saline (1 µL) were injected into the mPOA, and the variables were measured for additional 30 min. In a different group of rats, the AT-1 receptor, angiotensin II converting enzyme (ACE), and GABAa receptor gene expression was evaluated in mPOA samples by qPCR. The data are as mean ± SEM and submitted to One-way ANOVA (Tukey posttest) or paired Student t-test (P <0.05). Results: The injection of Ang II into the mPOA evoked a significant hypotension (-37±10 mmHg, n = 6, p = 0.024) and bradycardia (-47 ± 20 bpm, p = 0.030) compared to saline (+1 ± 1 mmHg and +6 ± 2 bpm, n = 6). A significant increase in IP was observed after Ang II injection into the mPOA (+72.25 ± 17.91%, p = 0.015 vs. -1.80 ± 2.98%, n = 6, saline). No significant changes were observed in MAP, HR and IP after the losartan injection in the mPOA compared to saline injection. Injection of GABA into the mPOA evoked a significant fall in MAP and HR (-68 ± 2 mmHg, n = 6, p < 0.0001 and -115 ± 14 bpm, n = 6, p = 0.0002 vs. -1 ± 1 mmHg and +4 ± 2 bpm, n = 6, saline), but no significant changes were observed in IP. The AT-1 receptor, ACE and GABAa receptor mRNA expression was observed in all mPOA samples. Discussion: Therefore, in female rats, Ang II mediated transmission in the mPOA is involved in the cardiovascular regulation and in the control of central micturition pathways. A phasic control dependent on AT-1 receptors in the mPOA seems to be involved in the regulation of those cardiovascular and intravesical 3 parameters. In contrast, GABAergic transmission in the mPOA participates in the pathways of cardiovascular control in anesthetized female rats, nevertheless, this neurotransmission is not involved in the micturition control.
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The shell Nucleus Accumbens (NAcc) projects to the lateral preoptic area, which is involved in the central micturition control and receives inputs from medullary areas involved in cardiovascular control. We investigated the role of GABAergic and glutamatergic transmission in the shell NAcc on intravesical pressure (IP) and cardiovascular control. Male Wistar rats with guide cannulas implanted bilaterally in the shell NAcc 7 days prior to the experiments were anesthetized with 2% isoflurane in 100% O2 and subjected to cannulation of the femoral artery and vein for mean arterial pressure (MAP) and heart rate recordings (HR) and infusion of drugs, respectively. The urinary bladder (UB) was cannulated for IP measurement. A Doppler flow probe was placed around the renal arterial for renal blood flow (RBF) measurement. After the baseline MAP, HR, IP and RBF recordings for 15 min, GABA or bicuculline methiodate (BMI) or L-glutamate or kynurenic acid (KYN) or saline (vehicle) were bilaterally injected into the shell NAcc and the variables were measured for 30 min. Data are as mean ± SEM and submitted to StudentÌs t test. GABA injections into the shell NAcc evoked a significant fall in MAP and HR and increased IP and RC compared to saline. L-glutamate in the shell NAcc increased MAP, HR and IP and reduced RC. Injections of BMI and KYN elicited no changes in the variables recorded. Therefore, the GABAergic and glutamatergic transmissions in neurons in the shell NAcc are involved in the neural pathways responsible for the central cardiovascular control and UB regulation.
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Núcleo Accumbens , Vejiga Urinaria , Ratas , Animales , Masculino , Núcleo Accumbens/fisiología , Ratas Wistar , Ácido Glutámico , Ácido gamma-AminobutíricoRESUMEN
Mucositis is an inflammation of the gastrointestinal mucosa that debilitate the quality of life of patients undergoing chemotherapy treatments. In this context, antineoplastic drugs, such as 5-fluorouracil, provokes ulcerations in the intestinal mucosa that lead to the secretion of pro-inflammatory cytokines by activating the NF-κB pathway. Alternative approaches to treat the disease using probiotic strains show promising results, and thereafter, treatments that target the site of inflammation could be further explored. Recently, studies reported that the protein GDF11 has an anti-inflammatory role in several diseases, including in vitro and in vivo results in different experimental models. Hence, this study evaluated the anti-inflammatory effect of GDF11 delivered by Lactococcus lactis strains NCDO2118 and MG1363 in a murine model of intestinal mucositis induced by 5-FU. Our results showed that mice treated with the recombinant lactococci strains presented improved histopathological scores of intestinal damage and a reduction of goblet cell degeneration in the mucosa. It was also observed a significant reduction of neutrophil infiltration in the tissue in comparison to positive control group. Moreover, we observed immunomodulation of inflammatory markers Nfkb1, Nlrp3, Tnf, and upregulation of Il10 in mRNA expression levels in groups treated with recombinant strains that help to partially explain the ameliorative effect in the mucosa. Therefore, the results found in this study suggest that the use of recombinant L. lactis (pExu:gdf11) could offer a potential gene therapy for intestinal mucositis induced by 5-FU.
RESUMEN
OBJECTIVE: We aimed to investigate whether Single Nucleotide Polymorphisms present in the genes of tooth mineral tissues influence dental caries trajectory across the life course, and if there is an epistatic (gene-gene) interaction between these SNPs. METHODS: A representative sample of all 5,914 births from the 1982 Pelotas birth cohort study was prospectively investigated. Dental caries trajectory across the life course was assessed at 15(n = 888), 24(n = 720), and 31 years old(n = 539). Group-based trajectory modeling was used to identify distinct subgroups of individuals whose caries measurements followed a similar pattern over time. Genetic material was collected, and individuals were genotyped [rs4970957(TUFT1), rs1711437(MMP20), rs1784418(MMP20), rs2252070(MMP13), rs243847(MMP2), rs2303466(DLX3), rs11656951(DLX3), rs7501477(TIMP2), rs388286(BMP7), and rs5997096(TFIP11)]. Analyzes were performed for allele and genotype using logistic regression and generalized multifactor dimensionality reduction for epistatic interactions. RESULTS: The analyses included 678 individuals, those with allele C (OR=0.74, CI95%[0.59-0.92]), genotype CC in the additive effect (OR=0.52, CI95%[0.31-0.89]), and the genotype TC/CC in dominant effect (OR=0.72, CI95%[0.53-0.98]) on the rs243847(MMP2) were associated with low caries trajectory. Individuals with the allele T (OR=0.79, CI95%[0.64-0.98]) and the genotype TC/CC in dominant effect (OR=0.66, CI95%[0.47-0.95]) on the rs5997096(TFIP11) were associated with low caries trajectory. Positive epistatic interactions were observed involving two (MMP2 and BMP7; p = 0.006) and three (TUFT1, MMP2, and TFIP11; p<0.001) loci and high caries trajectory. CONCLUSIONS: Some SNPs present in the genes of tooth mineral tissues were associated with caries trajectory and epistatic interactions increasing the network of SNPs involved in individual caries experience. CLINICAL SIGNIFICANCE: Single nucleotide polymorphisms in the pathway of tooth mineral tissues genes may contribute significantly to the individual caries experience across the life course.