RESUMO
BACKGROUND: In modern animal husbandry, breeders pay increasing attention to improving sow nutrition during pregnancy and lactation to favor the health of neonates. Sow milk is a main food source for piglets during their first three weeks of life, which is not only a rich repository of essential nutrients and a broad range of bioactive compounds, but also an indispensable source of commensal bacteria. Maternal milk microorganisms are important sources of commensal bacteria for the neonatal gut. Bacteria from maternal milk may confer a health benefit on the host. METHODS: Sow milk bacteria were isolated using culturomics followed by identification using 16S rRNA gene sequencing. To screen isolates for potential probiotic activity, the functional evaluation was conducted to assess their antagonistic activity against pathogens in vitro and evaluate their resistance against oxidative stress in damaged Drosophila induced by paraquat. In a piglet feeding trial, a total of 54 newborn suckling piglets were chosen from nine sows and randomly assigned to three treatments with different concentrations of a candidate strain. Multiple approaches were carried out to verify its antioxidant function including western blotting, enzyme activity analysis, metabolomics and 16S rRNA gene amplicon sequencing. RESULTS: The 1240 isolates were screened out from the sow milk microbiota and grouped into 271 bacterial taxa based on a nonredundant set of 16S rRNA gene sequencing. Among 80 Pediococcus isolates, a new Pediococcus pentosaceus strain (SMM914) showed the best performance in inhibition ability against swine pathogens and in a Drosophila model challenged by paraquat. Pretreatment of piglets with SMM914 induced the Nrf2-Keap1 antioxidant signaling pathway and greatly affected the pathways of amino acid metabolism and lipid metabolism in plasma. In the colon, the relative abundance of Lactobacillus was significantly increased in the high dose SMM914 group compared with the control group. CONCLUSION: P. pentosaceus SMM914 is a promising probiotic conferring antioxidant capacity by activating the Nrf2-Keap1 antioxidant signaling pathway in piglets. Our study provided useful resources for better understanding the relationships between the maternal microbiota and offspring. Video Abstract.
Assuntos
Antioxidantes , Leite , Animais , Antioxidantes/análise , Antioxidantes/metabolismo , Bactérias , Drosophila/genética , Drosophila/metabolismo , Feminino , Proteína 1 Associada a ECH Semelhante a Kelch/análise , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Paraquat/análise , Paraquat/metabolismo , Pediococcus pentosaceus/genética , Pediococcus pentosaceus/metabolismo , Gravidez , RNA Ribossômico 16S/análise , SuínosRESUMO
This study investigated whether resveratrol could improve meat quality, muscular antioxidant capacity, lipid metabolism and fiber type composition of intrauterine growth retarded pigs. Thirty-six pairs of male normal birth weight and intrauterine growth retardation (IUGR) piglets were orally fed with 80â¯mg resveratrol/kg body weight/d or vehicle during the sucking period (7-21 d). Then the offspring were fed with a basal diet containing 300â¯mg resveratrol/kg or a basal diet from weaning to slaughter (150 d). The IUGR-impaired meat quality (luminance and yellowness) was associated with muscular oxidative stress via increased Keap1 protein level, fat accumulation, and higher MyHC IIb gene expression. Expectedly, resveratrol increased glutathione peroxidase activity and MyHC I gene expression, reduced protein carbonyl and malondialdehyde contents, enhanced fatty acid oxidation via upregulated PPARα and targeted genes expression, and thereby improving drip loss and yellowness. Results indicate that resveratrol improved meat quality of IUGR pigs through enhancing antioxidant capacity, increasing oxidative fiber composition, and suppressing lipid accumulation.
Assuntos
Retardo do Crescimento Fetal/veterinária , Carne de Porco/análise , Resveratrol/administração & dosagem , Sus scrofa/crescimento & desenvolvimento , Ração Animal/análise , Animais , Antioxidantes , Dieta/veterinária , Feminino , Regulação da Expressão Gênica , Proteína 1 Associada a ECH Semelhante a Kelch/análise , Metabolismo dos Lipídeos , Masculino , Fibras Musculares Esqueléticas , Estresse OxidativoRESUMO
AIMS: Oxidative stress markers and antioxidant enzymes have previously been shown to have prognostic value and associate with adverse outcome in patients with diffuse large B cell lymphoma (DLBCL). Nuclear factor erythroid 2-related factor 1 (Nrf1) and factor 2 (Nrf2) are among the principal inducers of antioxidant enzyme production. Kelch ECH associating protein 1 (Keap1) is a negative regulator of Nrf2, and BTB (BR-C, ttk and bab) domain and CNC homolog 1 (Bach1) represses the function of both factors. Their significance in DLBCL prognosis is unknown. METHODS: Diagnostic biopsy samples of 76 patients with high-risk DLBCL were retrospectively stained with immunohistochemistry for Nrf1, Nrf2, Keap1 and Bach1, and correlated with clinical data and outcome. RESULTS: Nuclear Nrf2 and nuclear Bach1 expression were associated with adverse clinical features (anaemia, advanced stage, high IPI, high risk of neutropaenic infections), whereas cytoplasmic Nrf1 and Nrf2 were associated with favourable clinical presentation (normal haemoglobin level, no B symptoms, limited stage). None of the evaluated factors could predict survival alone. However, when two of the following parameters were combined: high nuclear score of Nrf2, low nuclear score of Nrf1, high cytoplasmic score of Nrf1 and low cytoplasmic score of Keap1 were associated with significantly worse overall survival. CONCLUSIONS: Nrf1 and Nrf2 are relevant in disease presentation and overall survival in high-risk DLBCL. Low nuclear expression of Nrf1, high cytoplasmic expression of Nrf1, high nuclear expression of Nrf2 and low cytoplasmic expression of Keap1 are associated with adverse outcome in this patient group.
Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores Tumorais/análise , Linfoma Difuso de Grandes Células B/química , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Fator 1 Relacionado a NF-E2/análise , Fator 2 Relacionado a NF-E2/análise , Rituximab/administração & dosagem , Adulto , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Fatores de Transcrição de Zíper de Leucina Básica/análise , Núcleo Celular/química , Núcleo Celular/patologia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Citoplasma/química , Citoplasma/patologia , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Humanos , Imuno-Histoquímica , Proteína 1 Associada a ECH Semelhante a Kelch/análise , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Rituximab/efeitos adversos , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Adulto JovemRESUMO
Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a major regulator of the oxidative stress response and it is negatively regulated by Kelch-like ECH-associated protein 1 (Keap1). The Keap1-Nrf2 axis has a fundamental role in carcinogenesis. In previous studies, the widely used diabetes drug metformin has appeared to have a critical role in the regulation of Nrf2 function. In this study, we assessed the expression of Nrf2 and Keap1 immunohistochemically in 157 patients with type 2 diabetes who underwent breast cancer surgery with curative intent. In total, 78 (49.7%) of these patients were taking metformin alone or combined with other oral anti-diabetic medication at the time of breast cancer diagnosis. We found that high-level cytoplasmic Nrf2 expression predicted dismal overall survival and breast cancer-specific survival, but only in the patients who were not taking metformin at the time of diagnosis. Similarly, low-level nuclear Keap1 expression had an adverse prognostic value in terms of overall survival and breast cancer-specific survival in patients without metformin. On the other hand, high-level nuclear Keap1 expression was associated with prolonged overall survival and breast cancer-specific survival. The results may be explained in terms of non-functioning or displaced Keap1, although more mechanistic pre-clinical and prospective clinical studies are warranted.
Assuntos
Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Metformina/uso terapêutico , Fator 2 Relacionado a NF-E2/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Feminino , Seguimentos , Humanos , Hipoglicemiantes/uso terapêutico , Proteína 1 Associada a ECH Semelhante a Kelch/análise , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Pessoa de Meia-Idade , Fator 2 Relacionado a NF-E2/análise , Fator 2 Relacionado a NF-E2/metabolismo , Prognóstico , Análise de SobrevidaRESUMO
Acrolein, an α/ß-unsaturated aldehyde, is volatile at room temperature. It is a respiratory irritant found in environmental tobacco smoke, which can be generated during cooking or endogenously at sites of injury. An acute high concentration of uncontrolled irritant exposure can lead to an asthma-like syndrome known as reactive airways dysfunction syndrome (RADS). However, whether acrolein can induce RADS remains poorly understood. The aim of study is to develop a RADS model of acrolein inhalation in mice and to clarify the mechanism of RADS. Mice were treated with ovalbumin (OVA) and exposed to acrolein (5 ppm/10 min). Airway hyper-responsiveness (AHR) was measured on days 24 and 56, and samples were collected on days 25 and 57. Tight junction protein, antioxidant-associated protein, and vascular endothelial growth factor (VEGF) levels were estimated by Western blotting and immunohistochemical staining. Reactive oxygen species (ROS) was calculated using enzyme linked immunosorbent assays. Acrolein or OVA groups exhibited an increase in airway inflammatory cells and AHR compared to a sham group. These effects were further increased in mice in the OVA + acrolein exposure group than in the OVA exposure group and persisted in the acrolein exposure group for 8 weeks. CLDNs, carbonyls, VEGF, Nrf2, and Keap1 were observed in the lungs. Our data demonstrate that acrolein induces RADS and that ROS, angiogenesis, and tight junction proteins are involved in RADS in a mouse model.