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Este texto objetiva analisar as condições para atuação futebolística das mulheres jogadoras da equipe Foz Cataratas após a associação realizada com o clube Athletico Paranaense em 2019. Para tanto optou-se por um estudo de caso realizado através de observações e entrevista semiestruturada aplicadas à quatorze jogadoras e ao dirigente. As narrativas foram analisadas com base na metodologia denominada Análise de Conteúdo (Bardim, 1979). Verificou-se que as ações fomentadas pelas entidades futebolísticas impactaram positivamente ao trazer oportunidades para um número maior de mulheres, mas não garantiu melhorias nas condições de atuação das jogadoras e não remeteu a profissionali-zação no futebol de mulheres, especialmente para equipes com baixo capital simbólico, localizadas fora dos centros futebolísticos (AU).
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Humanos , FemeninoRESUMEN
Este texto objetiva analisar as condições para atuação fu-tebolística das mulheres jogadoras da equipe Foz Cataratas após a associação realizada com o clube Athletico Paranaense em 2019. Para tanto optou-se por um estudo de caso realizado através de observações e entrevista semiestruturada aplicadas à quatorze jo-gadoras e ao dirigente. As narrativas foram analisadas com base na metodologia denominada Análise de Conteúdo (Bardim, 1979). Verificou-se que as ações fomentadas pelas entidades futebolísti-cas impactaram positivamente ao trazer oportunidades para um número maior de mulheres, mas não garantiu melhorias nas con-dições de atuação das jogadoras e não remeteu a profissionali-zação no futebol de mulheres, especialmente para equipes com baixo capital simbólico, localizadas fora dos centros futebolísticos.
The aim of this text is to analyze the conditions in which women players from the Foz Cataratas team can play football after the association with the Athletico Paranaense club in 2019. To this end, we opted for a case study carried out through observations and semi-structured interviews applied to fourteen female players and the manager. The narratives were analyzed using the methodology known as Content Analysis (Bardin, 1979). It was found that the actions promoted by soccer organizations had a positive impact by bringing opportunities to a greater number of women, but did not guarantee improvements in the playing conditions of the players and did not lead to the professionalization of women's soccer, especially for teams with low symbolic capital, located outside the soccer centers.
Este texto tiene como objetivo analizar las condiciones para el rendimiento futbolístico de las jugadoras del equipo Foz Cataratas después de la asociación con el club Athletico Paranaense en 2019. Para ello, optamos por un estudio de caso realizado a través de observaciones y entrevistas semiestructuradas con catorce jugadoras y el dirigente. Las narrativas fueron analizadas utilizando la metodología de Análisis de Contenido (Bardin, 1979). Se constató que las acciones promovidas por las organizaciones de fútbol tuvieron un impacto positivo al traer oportunidades a un mayor número de mujeres, pero no garantizaron mejoras en las condiciones de juego de las jugadoras y no condujeron a la profesionalización del fútbol femenino, especialmente para los equipos con bajo capital simbólico, localizados fuera de los centros futbolísticos.
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Treatments are only partially effective in major depressive disorders (MDD) but no biomarker exists to predict symptom improvement in patients. Animal models are essential tools in the development of antidepressant medications, but while recent genetic studies have demonstrated the polygenic contribution to MDD, current models are limited to either mimic the effect of a single gene or environmental factor. We developed in the past a model of depressive-like behaviors in mice (H/Rouen), using selective breeding based on behavioral reaction after an acute mild stress in the tail suspension test. Here, we propose a new mouse model of depression (H-TST) generated from a more complex genetic background and based on the same selection process. We first demonstrated that H/Rouen and H-TST mice had similar phenotypes and were more sensitive to glutamate-related antidepressant medications than selective serotonin reuptake inhibitors. We then conducted an exome sequencing on the two mouse models and showed that they had damaging variants in 174 identical genes, which have also been associated with MDD in humans. Among these genes, we showed a higher expression level of Tmem161b in brain and blood of our two mouse models. Changes in TMEM161B expression level was also observed in blood of MDD patients when compared with controls, and after 8-week treatment with duloxetine, mainly in good responders to treatment. Altogether, our results introduce H/Rouen and H-TST as the two first polygenic animal models of MDD and demonstrate their ability to identify biomarkers of the disease and to develop rapid and effective antidepressant medications.
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Antidepresivos , Biomarcadores , Trastorno Depresivo Mayor , Modelos Animales de Enfermedad , Herencia Multifactorial , Trastorno Depresivo Mayor/genética , Trastorno Depresivo Mayor/tratamiento farmacológico , Animales , Humanos , Ratones , Masculino , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Biomarcadores/sangre , Femenino , Adulto , Proteínas de la Membrana/genética , Ratones Endogámicos C57BL , Persona de Mediana Edad , Encéfalo/metabolismoRESUMEN
Autism spectrum disorder (ASD) is characterized by the presence of restricted/repetitive behaviors and social communication deficits. Because effective treatments for ASD remain elusive, novel therapeutic strategies are necessary. Preclinical studies show that L. reuteri selectively reversed social deficits in several models for ASD. Here, in a double-blind, randomized, placebo-controlled trial, we tested the effect of L. reuteri (a product containing a combination of strains ATCC-PTA-6475 and DSM-17938) in children with ASD. The treatment does not alter overall autism severity, restricted/repetitive behaviors, the microbiome composition, or the immune profile. However, L. reuteri combination yields significant improvements in social functioning that generalized across different measures. Interestingly, ATCC-PTA-6475, but not the parental strain of DSM-17938, reverses the social deficits in a preclinical mouse model for ASD. Collectively, our findings show that L. reuteri enhances social behavior in children with ASD, thereby warranting larger trials in which strain-specific effects should also be investigated.
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Trastorno del Espectro Autista , Trastorno Autístico , Niño , Ratones , Animales , Humanos , Trastorno Autístico/terapia , Trastorno del Espectro Autista/terapia , Conducta Social , Resultado del Tratamiento , Método Doble CiegoRESUMEN
The consumption of coffee and caffeine (1,3,7-trimethylxanthine) is part of many cultures worldwide. Their properties include serving as a neurostimulant aid, enhancing energy substrate levels, and improving general exercise performance. Both present therapeutic effects that can also be used to control chronic and metabolic diseases due to four mechanisms: adenosine receptor antagonism, increased catecholamine concentrations, a phosphodiesterase inhibitor, and a stimulator of calcium-release channels. Despite the individual genetic variabilities, distinct mechanisms have been demonstrated to improve physical performance, thermogenesis, lipolysis, insulin sensitivity, and hormonal modulation. Thus, coffee consumption and caffeine supplementation may enhance physical and mental performance and may improve metabolic variables, reducing oxidative stress, inflammation, and insulin resistance. Current data reveal vital aspects of coffee and caffeine consumption in specific populations, although further studies are needed to define clinical interventions with caffeine in obesity and chronic conditions.
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Cafeína , Resistencia a la Insulina , Humanos , Cafeína/farmacología , Cafeína/metabolismo , Café/química , Ejercicio Físico , Antagonistas de Receptores Purinérgicos P1/farmacología , ObesidadRESUMEN
Critical COVID-19 has been associated with altered patterns of cytokines. Distinct inflammatory processes in systemic and pulmonary sites have been reported, but studies comparing these two sites are still scarce. We aimed to evaluate the profile of pulmonary and systemic cytokines and chemokines in critically ill COVID-19 patients. Levels of cytokines and chemokines were measured in plasma samples and minibronchoalveolar lavage of critical COVID-19 patients within 48 h and 5-8 days after intubation. Distinct inflammatory processes were observed in the lungs and blood, which were regulated separately. Survivor patients showed higher lung cytokine levels including IFN-γ, IL-2, IL-4, G-CSF, and CCL4, while nonsurvivors displayed higher levels in the blood, which included IL-6, CXCL8, CXCL10, CCL2, and CCL4. Furthermore, our findings indicate that high TNF and CXCL8 levels in the mini-BAL were associated with better lung oxygen exchange capacity, whereas high levels of IFN-γ in plasma were associated with worse lung function, as measured using the PaO2/FiO2 ratio. These results suggest that a robust and localized inflammatory response in the lungs is protective and associated with survival, whereas a systemic inflammatory response is detrimental and associated with mortality in critical COVID-19.
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COVID-19 , Humanos , Citocinas , Plasma , Inflamación , PulmónRESUMEN
COVID-19 has infected humans worldwide, causing millions of deaths or prolonged symptoms in survivors. The transient or persistent symptoms after SARS-CoV-2 infection have been defined as post-COVID-19 conditions (PCC). We conducted a study of 151 Brazilian PCC patients to analyze symptoms and immunoglobulin profiles, taking into account sex, vaccination, hospitalization, and age. Fatigue and myalgia were the most common symptoms, and lack of vaccination, hospitalization, and neuropsychiatric and metabolic comorbidities were relevant to the development of PCC. Analysis of serological immunoglobulins showed that IgA was higher in PCC patients, especially in the adult and elderly groups. Also, non-hospitalized and hospitalized PCC patients produced high and similar levels of IgA. Our results indicated that the detection of IgA antibodies against SARS-CoV-2 during the course of the disease could be associated with the development of PCC and may be an immunological signature to predict prolonged symptoms in COVID-19 patients.
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COVID-19 , Inmunoglobulina A , Adulto , Anciano , Humanos , SARS-CoV-2 , Brasil/epidemiología , Hospitalización , Anticuerpos Antivirales , Inmunoglobulina MRESUMEN
BACKGROUND: The use of probiotic lactic acid bacteria as a mucosal vaccine vector is considered a promising alternative compared to the use of other microorganisms because of its "Generally Regarded as Safe" status, its potential adjuvant properties, and its tolerogenicity to the host. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease (COVID-19), is highly transmissible and pathogenic. This study aimed to determine the potential of Lactiplantibacillus plantarum expressing SARS-CoV-2 epitopes as a mucosal vaccine against SARS-CoV-2. RESULTS: In this study, the possible antigenic determinants of the spike (S1-1, S1-2, S1-3, and S1-4), membrane (ME1 and ME2), and envelope (E) proteins of SARS-CoV-2 were predicted, and recombinant L. plantarum strains surface-displaying these epitopes were constructed. Subsequently, the immune responses induced by these recombinant strains were compared in vitro and in vivo. Most surface-displayed epitopes induced pro-inflammatory cytokines [tumor necrosis factor alpha (TNF-α and interleukin (IL)-6] and anti-inflammatory cytokines (IL-10) in lipopolysaccharide-induced RAW 264.7, with the highest anti-inflammatory to pro-inflammatory cytokine ratio in the S1-1 and S1-2 groups, followed by that in the S1-3 group. When orally administered of recombinant L. plantarum expressing SARS-CoV-2 epitopes in mice, all epitopes most increased the expression of IL-4, along with induced levels of TNF-α, interferon-gamma, and IL-10, specifically in spike protein groups. Thus, the surface expression of epitopes from the spike S1 protein in L. plantarum showed potential immunoregulatory effects, suggesting its ability to potentially circumvent hyperinflammatory states relevant to monocyte/macrophage cell activation. At 35 days post immunization (dpi), serum IgG levels showed a marked increase in the S1-1, S1-2, and S1-3 groups. Fecal IgA levels increased significantly from 21 dpi in all the antigen groups, but the boosting effect after 35 dpi was explicitly observed in the S1-1, S1-2, and S1-3 groups. Thus, the oral administration of SARS-CoV-2 antigens into mice induced significant humoral and mucosal immune responses. CONCLUSION: This study suggests that L. plantarum is a potential vector that can effectively deliver SARS-CoV-2 epitopes to intestinal mucosal sites and could serve as a novel approach for SARS-CoV-2 mucosal vaccine development.
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COVID-19 , SARS-CoV-2 , Animales , Ratones , Humanos , Interleucina-10 , Inmunidad Mucosa , Epítopos , Factor de Necrosis Tumoral alfa , Vacunas contra la COVID-19 , COVID-19/prevención & control , Inmunización , CitocinasRESUMEN
AIMS: Millions of people died during the COVID-19 pandemic, but the vast majority of infected individuals survived. Now, some consequences of the disease, known as long COVID, are been revealed. Although the respiratory system is the target of Sars-CoV-2, COVID-19 can influence other parts of the body, including bone. The aim of this work was to investigate the impact of acute coronavirus infection in bone metabolism. MAIN METHODS: We evaluated RANKL/OPG levels in serum samples of patients with and without acute COVID-19. In vitro, the effects of coronavirus in osteoclasts and osteoblasts were investigated. In vivo, we evaluated the bone phenotype in a BSL2 mouse model of SARS-like disease induced by murine coronavirus (MHV-3). KEY FINDINGS: Patients with acute COVID-19 presented decreased OPG and increased RANKL/OPG ratio in the serum versus healthy individuals. In vitro, MHV-3 infected macrophages and osteoclasts, increasing their differentiation and TNF release. Oppositely, osteoblasts were not infected. In vivo, MHV-3 lung infection triggered bone resorption in the femur of mice, increasing the number of osteoclasts at 3dpi and decreasing at 5dpi. Indeed, apoptotic-caspase-3+ cells have been detected in the femur after infection as well as viral RNA. RANKL/OPG ratio and TNF levels also increased in the femur after infection. Accordingly, the bone phenotype of TNFRp55-/- mice infected with MHV-3 showed no signs of bone resorption or increase in the number of osteoclasts. SIGNIFICANCE: Coronavirus induces an osteoporotic phenotype in mice dependent on TNF and on macrophage/osteoclast infection.
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Resorción Ósea , COVID-19 , Animales , Humanos , Ratones , Resorción Ósea/metabolismo , Diferenciación Celular , COVID-19/metabolismo , Osteoblastos , Osteoclastos/metabolismo , Osteoprotegerina/metabolismo , Pandemias , Fenotipo , Síndrome Post Agudo de COVID-19 , Ligando RANK/metabolismo , SARS-CoV-2/metabolismo , Virus de la Hepatitis Murina/metabolismo , Virus de la Hepatitis Murina/patogenicidad , Infecciones por Coronavirus/genética , Infecciones por Coronavirus/metabolismoRESUMEN
The blood levels of neutrophils are associated with the severity of COVID -19. However, their role in the pulmonary environment during COVID -19 severity is not clear. Here, we found a decrease in the neutrophil count in BAL (bronchoalveolar lavage) in non-survivors and in older patients (> 60 years). In addition, we have shown that older patients have higher serum concentration of CXCL8 and increased IL-10 expression by neutrophils.
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COVID-19 , Neutrófilos , Humanos , Anciano , Líquido del Lavado Bronquioalveolar , Pulmón , PronósticoRESUMEN
Surströmming, a Swedish fermented fish, loved by some and avoided by others, occurs in many reports on improved or cured gastrointestinal problems even by a single meal. We tested the hypothesis that the microbes of the fermented food might have a potency to modify the gut microbiome. Two groups of voluntary participants (11 male, 8 female; aged 20-80 years) were exposed to a single meal containing the fish. A 7-day dietary intervention was carried out comprising the fish as the main source of protein in a single adult. The microbiome was characterized using 16S rRNA and metagenomic sequencing. Individual community-level changes in the microbiome were compared, as well as the presence of bacteria associated with the fermented fish. We focused on Shannon alpha and UniFrac beta diversity. We did not detect any global changes in the gut microbiome in response to Surströmming, nor were we able to recover and identify any members of Halanaerobium, which were associated with and abundant in the ingested fish, in the stool samples of the participants. Our results suggest that Surströmming consumption does not alter the microbiome of healthy individuals. However, beneficial effects on a diseased gut, impaired gut microbiome, or other effects in disease remain to be studied.
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Bacterias , Microbioma Gastrointestinal , Animales , Masculino , Femenino , ARN Ribosómico 16S/genética , Heces/microbiología , Microbioma Gastrointestinal/genéticaRESUMEN
Recent evidence shows the cardiometabolic effects of estrogen administration in postmenopausal women. Women have a cardiometabolic advantage during their reproductive years, which is lost at menopause due to declining estradiol (E2). E2, also known as 17-beta-estradiol, has diverse effects in its target tissues, including the cardiovascular (CV) system, through genomic and non-genomic signaling. Metabolic changes characteristic of menopause include a worsening lipid profile, changes in body fat distribution, epicardial and pericardial fat deposition, increased susceptibility to weight gain, and increased blood pressure, resulting in an increased risk of accelerated cardiovascular disease (CVD) development. E2 mediates its cardioprotective actions by increasing mitochondrial biogenesis, angiogenesis, and vasodilation, decreasing reactive oxygen species (ROS) and oxidative stress, and modulating the renin-angiotensin-aldosterone system (RAAS). In this review, we assess whether it is prudent to develop an approach to managing postmenopausal women based on modifying the patient's CV risk that includes human-identical hormone replacement therapy (HRT), modulation of RAAS, and stimulating mitochondrial biogenesis. Further research is needed to assess the safety and benefit of HRT to reduce cardiometabolic risk.
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Enfermedades Cardiovasculares , Sistema Renina-Angiotensina , Femenino , Humanos , Posmenopausia/fisiología , Terapia de Reemplazo de Estrógeno/efectos adversos , Terapia de Reemplazo de Estrógeno/métodos , Biogénesis de Organelos , Menopausia/fisiología , Terapia de Reemplazo de Hormonas , Estradiol/farmacología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & controlRESUMEN
INTRODUCTION: Diabetes mellitus (T2DM) and cardiovascular diseases (CVDs) have become some of the most urgent and prevalent health problems in recent decades, side by side with the growing obesity crisis. The close relationship between T2DM and CVD has become clear: endothelial dysfunction caused by oxidative stress and inflammation resulting from hyperglycaemia are the key factors in the development of vascular complications of T2DM, leading to CVD. Coenzyme Q10 (CoQ10) is a great candidate for the treatment of these diseases, acting precisely at the intersection between T2DM and CVD that is oxidative stress, due to its strong antioxidant activity and fundamental physiological role in mitochondrial bioenergetics. CoQ10 is a biologically active liposoluble compound comprising a quinone group and a side chain of 10 isoprenoid units, which is synthesized endogenously in the body from tyrosine and mevalonic acid. The main biochemical action of CoQ10 is as a cofactor in the electron transport chain that synthesizes adenosine triphosphate (ATP). As most cellular functions depend on an adequate supply of ATP, CoQ10 is essential for the health of virtually all human tissues and organs. CoQ10 supplementation has been used as an intensifier of mitochondrial function and an antioxidant with the aim of palliating or reducing oxidative damage that can worsen the physiological outcome of a wide range of diseases including T2DM and CVDs. CONCLUSION: Although there is not enough evidence to conclude it is effective for different therapeutic indications, CoQ10 supplementation is probably safe and well-tolerated, with few drug interactions and minor side effects. Many valuable advances have been made in the use of CoQ10 in clinical practice for patients with T2DM and a high risk of CVD. However, further research is needed to assess the real safety and benefit to indicate CoQ10 supplementation in patients with T2DM.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Humanos , Enfermedades Cardiovasculares/tratamiento farmacológico , Ubiquinona/uso terapéutico , Antioxidantes/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Adenosina TrifosfatoRESUMEN
Severe cases of COVID-19 present hyperinflammatory condition that can be fatal. Little is known about the role of regulatory responses in SARS-CoV-2 infection. In this study, we evaluated the phenotype of regulatory T cells in the blood (peripheral blood mononuclear cell) and the lungs (broncho-alveolar) of adult patients with severe COVID-19 under invasive mechanical ventilation. Our results show important dynamic variation on Treg cells phenotype during COVID-19 with changes in number and functional parameters from the day of intubation (Day 1 of intensive care unit admission) to Day 7. We observed that compared with surviving patients, non-survivors presented lower numbers of Treg cells in the blood. In addition, lung Tregs of non-survivors also displayed higher PD1 and lower FOXP3 expressions suggesting dysfunctional phenotype. Further signs of Treg dysregulation were observed in non-survivors such as limited production of IL-10 in the lungs and higher production of IL-17A in the blood and in the lungs, which were associated with increased PD1 expression. These findings were also associated with lower pulmonary levels of Treg-stimulating factors like TNF and IL-2. Tregs in the blood and lungs are profoundly dysfunctional in non-surviving COVID-19 patients.
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COVID-19 , Linfocitos T Reguladores , Humanos , Linfocitos T Reguladores/metabolismo , Leucocitos Mononucleares/metabolismo , SARS-CoV-2/metabolismo , Pulmón/metabolismo , Fenotipo , Factores de Transcripción Forkhead/metabolismoRESUMEN
BACKGROUND: The effects of proton-pump inhibitors (PPIs) on the infant microbiome remain unclear. Swedish pilot cohort study to assess the longitudinal effect of long-term PPI on the infant gut microbiome, including ten newborn infants operated for esophageal atresia exposed to PPIs (mean 57 weeks), compared to healthy one-year-old controls. All children were born vaginally and were otherwise healthy. Within- and between sample diversity of the fecal microbiome was assessed using untargeted whole genome Shotgun metagenomics which sequences all the DNA in the sample and can capture genes rather than a taxonomic fingerprint. RESULTS: A longer duration of PPI-use was associated with considerable changes in evenness and high variation on diversity within samples compared to a shorter duration of use. The limited difference between baseline samples and controls suggests that this shift was most likely due to the drug exposure and not the underlying alterations on the microbiome. We found no associations with the number of antibiotic treatment episodes among the PPI-users. CONCLUSION: Prolonged PPI-use may alter the early infant gut microbiome composition, especially those with the most prolonged duration of use.
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INTRODUCTION: The management of patients with dyslipidemia (DLP) requires intensive medical follow-up as an essential part of treatment and to reduce the risk of cardiovascular (CV) outcomes. The aim of this study was to evaluate whether adherence to medical treatment changed the prevalence of CV disease events in a retrospective 7-year follow-up analysis. METHODS: This retrospective study involved 92 patients divided into two groups according to their adherence: the REG group with 64 patients who had medical appointments from 2012 to 2018, and the DROP group, with 28 patients who had medical appointments in 2012 but did not complete regular appointments until 2018. Cox proportional hazard models were fitted to estimate hazard ratios associated with CV outcomes as primary endpoints. RESULTS: We observed a total of 32 cases of acute myocardial infarction (AMI) in the study population, 17 (338.41 pY) in the REG group and 15 (62.97 pY) in the DROP group. An increased hazard of AMIs was observed in the DROP group compared with the REG group by follow-up time (p < 0.001). We found that previous events of AMI and congestive heart failure (CHF) were associated with progression to treatment dropout (p < 0.05) and that two drugs were considered a risk factor for treatment dropout, diuretics and fibrates (p < 0.05). CONCLUSIONS: A reduced hazard of AMI was observed in patients who complete a greater number of medical appointments and receive multidisciplinary treatment on a regular basis.
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Infectious diseases caused by mucosal pathogens significantly increase mortality and morbidity. Thus, the possibility to target these pathogens at their primary entry points can consolidate protective immunity. Regarding SARS-CoV-2 infection, it has been observed that the upper respiratory mucosa is highly affected and that dysregulation of resident microbiota in the gut-lung axis plays a crucial role in determining symptom severity. Thus, understanding the possibility of eliciting various mucosal and adaptive immune responses allows us to effectively design bacterial mucosal vaccine vectors. Such design requires rationally selecting resident bacterial candidates as potential host carriers, evaluating effective carrier proteins for stimulating an immune response, and combining these two to improve antigenic display and immunogenicity. This review investigated mucosal vaccine vectors from 2015 to present, where a few have started to utilize Salmonella and lactic acid bacteria (LAB) to display SARS-CoV-2 Spike S proteins or fragments. Although current literature is still lacking for its studies beyond in vitro or in vivo efficiency, decades of research into these vectors show promising results. Here, we discuss the mucosal immune systems focusing on the gut-lung axis microbiome and offer new insight into the potential use of alpha streptococci in the upper respiratory tract as a vaccine carrier.
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Background: Asthma is a chronic pulmonary disease that affects about 300 million people worldwide. Previous studies have associated antimicrobial use with allergies, but the real impact of antibiotics on asthma is still elusive. We investigated the potential impact of amoxicillin (Amox), trimethoprim/sulfamethoxazole (TMP/SMX), and metronidazole (Metro) in a murine model of OVA-induced allergic airway inflammation. Methods: BALB/c mice received three cycles of 7 days of antibiotics in drinking water followed by 7 days washout and were sensitized i.p. with OVA/Alum at days 0 and 14. After the end of the last antibiotic washout, the mice were challenged with aerosolized OVA. Pulmonary parameters were evaluated, and serum, BAL, and feces were collected for analysis. Results: Amox- and TMP/SMX-treated animals displayed more severe allergic airway inflammation parameters with increased airway hyperresponsiveness, reduced lung alveolar volume, and increased levels in BAL of IL-4 and IL-6. In contrast, Metro-treated mice showed preserved FEV-50, decreased lung inflammation, and higher levels of butyrate and propionate in their feces. Metro treatment was associated with increased OVA-specific IgA in serum. BAL microbiota was abundant in allergic groups but not in nonallergic controls with the Amox-treated group displaying the increased frequency of Proteobacteria, while Metro and TMP/SMX showed increased levels of Firmicutes. In the gut, we observed the enrichment of Akkermansia muciniphila associated with reduced airway inflammation phenotype in the Metro group, even after the recovery period. Conclusion: Our data suggest that different antibiotic treatments may impact the course of experimental allergic airway inflammation in diverse ways by several mechanisms, including modulation of short-chain fat acids production by intestinal microbiota.
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Asma , Hipersensibilidad , Microbiota , Animales , Antibacterianos/uso terapéutico , Asma/tratamiento farmacológico , Humanos , Hipersensibilidad/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Pulmón , Ratones , Combinación Trimetoprim y SulfametoxazolRESUMEN
BACKGROUND: Epidemiological and experimental studies have shown a protective effect of helminth infections in weight gain and against the development of metabolic dysfunctions in the host. However, the mechanisms Treg cells exert in the helminth-obesity interface has been poorly investigated. The present study aimed to verify the influence of Heligmosomoides polygyrus infection in early stages of high fat diet-induced obesity. PRINCIPAL FINDINGS: The presence of infection was able to prevent exacerbated weight gain in mice fed with high fat diet when compared to non-infected controls. In addition, infected animals displayed improved insulin sensitivity and decreased fat accumulation in the liver. Obesity-associated inflammation was reduced in the presence of infection, demonstrated by lower levels of leptin and resistin, lower infiltration of Th1 and Th17 cells in adipose tissue, higher expression of IL10 and adiponectin, increased infiltration of Th2 and eosinophils in adipose tissue of infected animals. Of note, the parasite infection was associated with increased Treg frequency in adipose tissue which showed higher expression of cell surface markers of function and activation, like LAP and CD134. The infection could also increase adipose Treg suppressor function in animals on high fat diet. CONCLUSION: These data suggest that H. polygyrus modulates adipose tissue Treg cells with implication for weight gain and metabolic syndrome.
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Dieta Alta en Grasa , Resistencia a la Insulina , Tejido Adiposo , Animales , Dieta Alta en Grasa/efectos adversos , Resistencia a la Insulina/fisiología , Ratones , Ratones Endogámicos C57BL , Obesidad/metabolismo , Aumento de PesoRESUMEN
The flavonoid myricitrin showed an antidepressant-like effect in the tail suspension test and increased hippocampal neurogenesis, as well as demonstrating anti-inflammatory effects. Interestingly, inflammation has been linked to depression, and anti-inflammatory drugs showed promising results as antidepressant-like drugs. Thus, the present study evaluated the effects of myricitrin in the chronic mild stress (CMS) model, a translational and valid animal model of depression, using the mini-experiment design to improve the reproducibility of the findings. The sucrose preference test (SPT), forced swim test (FST), and tail suspension test (TST) were the readouts of depressive-like phenotypes induced by CMS. Relative adrenal weight was employed as an index of the hypothalamus-pituitary-adrenal (HPA) axis activation. Interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha levels were measured in the hippocampus. Myricitrin (10 mg/kg, intraperitoneally, for 14 days) reversed depressive-like behaviors induced by CMS (increased immobility in the FST, the TST and anhedonia), as well as decreased adrenal hypertrophy and hippocampal levels of IL-6 in stressed mice. Similar results were observed by imipramine (20 mg/kg, intraperitoneally, for 14 days), a serotonin and norepinephrine reuptake inhibitor (positive control). A significant correlation was observed between immobility time in the TST, and hippocampal IL-6 levels. Hippocampal TNF-α levels were not affected by CMS or drug treatment. In conclusion, myricitrin exhibited an antidepressant-like profile in CMS, and this effect may be associated with its anti-inflammatory activity.