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1.
Int J Mol Sci ; 23(18)2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36142723

RESUMO

Previous works have described the activity of Bifidobacterium longum subsp. infantis CECT 7210 (also commercially named B. infantis IM-1®) against rotavirus in mice and intestinal pathogens in piglets, as well as its diarrhea-reducing effect on healthy term infants. In the present work, we focused on the intestinal immunomodulatory effects of B. infantis IM-1® and for this purpose we used the epithelial cell line isolated from colorectal adenocarcinoma Caco-2 and a co-culture system of human dendritic cells (DCs) from peripheral blood together with Caco-2 cells. Single Caco-2 cultures and Caco-2: DC co-cultures were incubated with B. infantis IM-1® or its supernatant either in the presence or absence of Escherichia coli CECT 515. The B. infantis IM-1® supernatant exerted a protective effect against the cytotoxicity caused by Escherichia coli CECT 515 on single cultures of Caco-2 cells as viability reached the values of untreated cells. B. infantis IM-1® and its supernatant also decreased the secretion of pro-inflammatory cytokines by Caco-2 cells and the co-cultures incubated in the presence of E. coli CECT 515, with the response being more modest in the latter, which suggests that DCs modulate the activity of Caco-2 cells. Overall, the results obtained point to the immunomodulatory activity of this probiotic strain, which might underlie its previously reported beneficial effects.


Assuntos
Infecções por Escherichia coli , Probióticos , Animais , Bifidobacterium/fisiologia , Bifidobacterium longum subspecies infantis/metabolismo , Células CACO-2 , Citocinas/metabolismo , Escherichia coli/metabolismo , Humanos , Lactente , Camundongos , Probióticos/farmacologia , Suínos
2.
BMC Cancer ; 19(1): 495, 2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31126257

RESUMO

BACKGROUND: Breast cancer ranks first in women, and is the second cause of death in this gender. In addition to genetics, the environment contributes to the development of the disease, although the factors involved are not well known. Among the latter is the influence of microorganisms and, therefore, attention is recently being paid to the mammary microbiota. We hypothesize that the risk of breast cancer could be associated with the composition and functionality of the mammary/gut microbiota, and that exposure to environmental contaminants (endocrine disruptors, EDCs) might contribute to alter these microbiota. METHODS: We describe a case-control clinical study that will be performed in women between 25 and 70 years of age. Cases will be women diagnosed and surgically intervened of breast cancer (stages I and II). Women with antecedents of cancer or advanced tumor stage (metastasis), or who have received antibiotic treatment within a period of 3 months prior to recruitment, or any neoadjuvant therapy, will be excluded. Controls will be women surgically intervened of breast augmentation or reduction. Women with oncological, gynecological or endocrine history, and those who have received antibiotic treatment within a period of 3 months prior to recruitment will also be excluded. Blood, urine, breast tissue and stool samples will be collected. Data regarding anthropometric, sociodemographic, reproductive history, tumor features and dietary habits will be gathered. Metabolomic studies will be carried out in stool and breast tissue samples. Metagenomic studies will also be performed in stool and breast tissue samples to ascertain the viral, fungal, bacterial and archaea populations of the microbiota. Quantitation of estrogens, estrogen metabolites and EDCs in samples of serum, urine and breast tissue will also be performed. DISCUSSION: This is the first time that the contribution of bacteria, archaea, viruses and fungi together with their alteration by environmental contaminants to the risk of breast cancer will be evaluated in the same study. Results obtained could contribute to elucidate risk factors, improve the prognosis, as well as to propose novel intervention studies in this disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT03885648 , 03/25/2019. Retrospectively registered.


Assuntos
Neoplasias da Mama/microbiologia , Mama/microbiologia , Disbiose/microbiologia , Microbioma Gastrointestinal , Adulto , Idoso , Biópsia , Mama/patologia , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Neoplasias da Mama/urina , Estudos de Casos e Controles , Dano ao DNA , Exposição Ambiental/efeitos adversos , Estrogênios/análise , Fezes/microbiologia , Feminino , Humanos , Metaboloma , Pessoa de Meia-Idade , Inquéritos e Questionários
3.
BMC Complement Altern Med ; 18(1): 306, 2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30453950

RESUMO

BACKGROUND: Obesity is characterized by increased fat mass and is associated with the development of insulin resistance syndrome (IRS), usually known as metabolic syndrome. The alteration of the intestinal microbiota composition has a role in the development of IRS associated with obesity, and probiotics, which are live microorganisms that confer a health benefit to the host, contribute to restore intestinal microbiota homeostasis and lower peripheral tissue insulin resistance. We aim to evaluate the effects of the probiotic strain Lactobacillus reuteri (L. reuteri) V3401 on the composition of intestinal microbiota, markers of insulin resistance and biomarkers of inflammation, cardiovascular risk, and hepatic steatosis in patients with overweight and obesity exhibiting IRS. METHODS/DESIGN: We describe a randomized, double-blind, crossover, placebo-controlled, and single-centre trial. Sixty participants (aged 18 to 65 years) diagnosed with IRS will be randomized in a 1:1 ratio to receive either a daily dose of placebo or 5 × 109 colony-forming units of L. reuteri V3401. The study will consist of two intervention periods of 12 weeks separated by a washout period of 6 weeks and preceded by another washout period of 2 weeks. The primary outcome will be the change in plasma lipopolysaccharide (LPS) levels at 12 weeks. Secondary outcomes will include anthropometric parameters, lipid profile, glucose metabolism, microbiota composition, hepatic steatosis, and inflammatory and cardiovascular biomarkers. Blood and stool samples will be collected at baseline, at the midpoint (only stool samples) and immediately after each intervention period. Luminex technology will be used to measure interleukins. For statistical analysis, a mixed ANOVA model will be employed to calculate changes in the outcome variables. DISCUSSION: This is the first time that L. reuteri V3401 will be evaluated in patients with IRS. Therefore, this study will provide valuable scientific information about the effects of this strain in metabolic syndrome patients. TRIAL REGISTRATION: The trial has been retrospectively registered in ClinicalTrials.gov on the 23rd November 2016 (ID: NCT02972567 ), during the recruitment phase.


Assuntos
Limosilactobacillus reuteri/fisiologia , Síndrome Metabólica/tratamento farmacológico , Obesidade/tratamento farmacológico , Probióticos/administração & dosagem , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/imunologia , Método Duplo-Cego , Fígado Gorduroso/sangue , Fígado Gorduroso/etiologia , Fígado Gorduroso/genética , Fígado Gorduroso/imunologia , Feminino , Microbioma Gastrointestinal , Humanos , Resistência à Insulina , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/imunologia , Síndrome Metabólica/microbiologia , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/imunologia , Obesidade/microbiologia , Fatores de Risco , Adulto Jovem
4.
Hepatology ; 57(3): 995-1004, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23081825

RESUMO

UNLABELLED: The prevalence of the metabolic syndrome and nonalcoholic fatty liver disease (NAFLD) in humans increases with age. It is unknown whether this association is secondary to the increased incidence of risk factors for NAFLD that occurs with aging, reflects the culmination of years of exposure to lifestyle factors such as a high-fat diet (HFD), or results from physiological changes that characterize aging. To examine this question, the development of NAFLD in response to a fixed period of HFD feeding was examined in mice of different ages. Mice aged 2, 8, and 18 months were fed 16 weeks of a low-fat diet or HFD. Increased body mass and insulin insensitivity occurred in response to HFD feeding irrespective of the age of the mice. The amount of HFD-induced hepatic steatosis as determined biochemically and histologically was also equivalent among the three ages. Liver injury occurred exclusively in the two older ages as reflected by increased serum alanine aminotransferase levels, positive terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick end-labeling, and caspase activation. Older mice also had an elevated innate immune response with a more pronounced polarization of liver and adipose tissue macrophages into an M1 phenotype. Studies of cultured hepatocytes from young and old mice revealed that aged cells were selectively sensitized to the Fas death pathway. CONCLUSION: Aging does not promote the development of hepatic steatosis but leads to increased hepatocellular injury and inflammation that may be due in part to sensitization to the Fas death pathway and increased M1 macrophage polarization.


Assuntos
Tecido Adiposo/patologia , Envelhecimento/patologia , Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/patologia , Animais , Morte Celular/fisiologia , Gorduras na Dieta/farmacologia , Modelos Animais de Doenças , Fígado Gorduroso/epidemiologia , Fígado Gorduroso/imunologia , Hepatócitos/citologia , Humanos , Incidência , Resistência à Insulina/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica , Prevalência , Cultura Primária de Células , Fatores de Risco , Receptor fas/metabolismo
5.
Mol Nutr Food Res ; : e2400253, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38950423

RESUMO

SCOPE: This work is part of the clinical study NCT03885648 registered in ClinicalTrials.gov, aimed at studying the relationship among breast cancer, microbiota, and exposure to environmental pollutants. As a first step, we characterized and evaluated risk factors of the participants. METHODS AND RESULTS: A case-control study was designed with breast cancer (cases, n = 122) and healthy women (controls, n = 56) recruited in two hospitals of Andalusia (Southern Spain). Participants answered questionnaires of Mediterranean diet adherence and food frequency. Data were collected from medical histories and microbiota was analyzed on stool samples. Most cases (78.2%) were diagnosed as stages I and II. Cases had higher age, body mass index (BMI), glucose, cholesterol, and potassium values than controls. Cases exhibited higher adherence to the Mediterranean diet and their food consumption was closer to that dietary pattern. A hierarchical cluster analysis revealed that the Bacillota/Bacteroidota ratio was the most relevant variable in women with breast cancer, which was higher in this group compared with controls. CONCLUSION: Although cases exhibited higher adherence to the Mediterranean diet compared with controls, they presented features and microbiota alterations typical of the metabolic syndrome, probably due to their higher BMI and reflecting changes in their lifestyle around the time of diagnosis.

6.
Br J Nutr ; 109 Suppl 2: S27-34, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23360878

RESUMO

Ideally, cell models should resemble the in vivo conditions; however, in most in vitro experimental models, epithelial cells are cultivated as monolayers, in which the establishment of functional epithelial features is not achieved. To overcome this problem, co-culture experiments with probiotics, dendritic cells and intestinal epithelial cells and three-dimensional models attempt to reconcile the complex and dynamic interactions that exist in vivo between the intestinal epithelium and bacteria on the luminal side and between the epithelium and the underlying immune system on the basolateral side. Additional models include tissue explants, bioreactors and organoids. The present review details the in vitro models used to study host-microbe interactions and explores the new tools that may help in understanding the molecular mechanisms of these interactions.


Assuntos
Células Dendríticas/imunologia , Interações Hospedeiro-Parasita , Mucosa Intestinal/imunologia , Modelos Biológicos , Probióticos , Animais , Reatores Biológicos/microbiologia , Linhagem Celular , Células Cultivadas , Técnicas de Cocultura , Células Dendríticas/citologia , Células Dendríticas/microbiologia , Trato Gastrointestinal/citologia , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Interações Hospedeiro-Patógeno , Humanos , Mucosa Intestinal/citologia , Mucosa Intestinal/microbiologia , Macrófagos/citologia , Macrófagos/imunologia , Organoides/imunologia , Organoides/microbiologia , Técnicas de Cultura de Tecidos
7.
Br J Nutr ; 109 Suppl 2: S35-50, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23360880

RESUMO

According to the FAO and the WHO, probiotics are 'live microorganisms which, when administered in adequate amounts, confer a health benefit on the host'. The strains most frequently used as probiotics include lactic acid bacteria and bifidobacteria, which are isolated from traditional fermented products and the gut, faeces and breast milk of human subjects. The identification of microorganisms is the first step in the selection of potential probiotics. The present techniques, including genetic fingerprinting, gene sequencing, oligonucleotide probes and specific primer selection, discriminate closely related bacteria with varying degrees of success. Additional molecular methods, such as denaturing gradient gel electrophoresis/temperature gradient gel electrophoresis and fluorescence in situ hybridisation, are employed to identify and characterise probiotics. The ability to examine fully sequenced genomes has accelerated the application of genetic approaches to the elucidation of the functional roles of probiotics. One of the best-demonstrated clinical benefits of probiotics is the prevention and treatment of acute and antibiotic-associated diarrhoea;however, there is mounting evidence for a potential role for probiotics in the treatment of allergies and intestinal, liver and metabolic diseases. There are various mechanisms by which probiotics exert their beneficial effects: regulation of intestinal permeability, normalisation of host intestinal microbiota, improvement of gut immune barrier function, and adjustment between pro- and anti-inflammatory cytokines. The number of studies carried out to test the effects of probiotics in vitro and in animals is enormous. However, the most reliable method of assessing the therapeutic benefits of any probiotic strain is the use of randomised, placebo-controlled trials, which are reviewed in this article [corrected].


Assuntos
Bifidobacterium/crescimento & desenvolvimento , Bifidobacterium/isolamento & purificação , Trato Gastrointestinal/microbiologia , Lactobacillales/crescimento & desenvolvimento , Lactobacillales/isolamento & purificação , Probióticos/isolamento & purificação , Animais , Bifidobacterium/classificação , Bifidobacterium/imunologia , Produtos Fermentados do Leite/microbiologia , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/fisiologia , Humanos , Absorção Intestinal , Mucosa Intestinal/microbiologia , Lactobacillales/classificação , Lactobacillales/imunologia , Viabilidade Microbiana , Leite Humano/microbiologia , Permeabilidade , Probióticos/efeitos adversos , Probióticos/uso terapêutico
8.
Cancers (Basel) ; 15(2)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36672391

RESUMO

Breast cancer is the most frequently diagnosed cancer and also one of the leading causes of mortality among women. The genetic and environmental factors known to date do not fully explain the risk of developing this disease. In recent years, numerous studies have highlighted the dual role of the gut microbiota in the preservation of host health and in the development of different pathologies, cancer among them. Our gut microbiota is capable of producing metabolites that protect host homeostasis but can also produce molecules with deleterious effects, which, in turn, may trigger inflammation and carcinogenesis, and even affect immunotherapy. The purpose of this review is to describe the mechanisms by which the gut microbiota may cause cancer in general, and breast cancer in particular, and to compile clinical trials that address alterations or changes in the microbiota of women with breast cancer.

9.
Biomed J ; 44(3): 338-345, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34140269

RESUMO

BACKGROUND: The purpose of this study was to investigate the inflammatory response, lipid peroxidation and muscle damage in men and women athletes subjected to an acute resistance exercise. METHODS: Twenty college athletes (10 men and 10 women) performed a half-squat exercise consisting of five incremental intensities: 20%, 40%, 60%, 80% and 100% of the one-repetition maximum. Blood samples were collected at rest, 15 min and 24 h post-test. The concentration of lipid peroxidation markers and the activities of a skeletal muscle damage marker and a cardiac muscle damage marker were determined in serum. Serum α-actin was measured as a marker of sarcomere damage. Serum levels of interleukin-6, interleukin-10, and tumor necrosis factor alpha were determined to assess the inflammatory response. RESULTS: Interleukin-6 levels were higher at 24 h post-test than at rest and 15 min post-test in men (p < 0.05). Moreover, men showed significantly higher hydroperoxide levels in response to resistance exercise at 24 h post-test than at 15 min post-test (p < 0.05). No differences were found in muscle damage parameters regardless of sex or the time point of the test. No differences regarding the studied variables were found when comparing among different time points in women. CONCLUSION: Our results show a larger influence of half-squat exercises on the release of IL6 and on lipid peroxidation in men than in women at equivalent workloads.


Assuntos
Treinamento Resistido , Biomarcadores , Exercício Físico , Feminino , Humanos , Peroxidação de Lipídeos , Masculino , Músculo Esquelético
10.
Nutrients ; 13(1)2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33440736

RESUMO

Non-alcoholic fatty liver disease (NAFLD) has reached pandemic proportions worldwide. We have previously reported that the probiotic strains Bifidobacterium breve CNCM I-4035, Lactobacillus paracasei CNCM I-4034 and Lactobacillus rhamnosus CNCM I-4036 exert anti-inflammatory effects in the intestine of Zucker-Lepr fa/fa rats. In this work, we focused on their hepatic effects. M1 macrophages are related to inflammation and NAFLD pathogenesis, whereas M2 macrophages release anti-inflammatory mediators. We evaluated the effects of these 3 strains on macrophage polarization, inflammation and liver damage of Zucker-Lepr fa/fa rats. The animals received either a placebo or 1010 CFU of probiotics orally for 30 days. Nos2 and Cd86 mRNA levels were determined as markers of M1 macrophages, and Cd163 and Arg1 as M2 markers, respectively, by qRT-PCR. Liver damage was determined by lipid peroxidation, leukocyte infiltration and myeloperoxidase activity. We evaluated a panoply of circulating chemokines, the hepatic ratio P-Akt/Akt, NF-kB and P-NF-kB protein levels. All 3 probiotic strains modulated macrophage polarization in liver and circulating levels of inflammation-related mediators. L. paracasei CNCM I-4034 increased the ratio P-Akt/Akt and NF-kB protein levels. B. breve CNCM I-4035, L. paracasei CNCM I-4034 and L. rhamnosus CNCM I-4036 decreased both pro-inflammatory macrophage gene expression and leukocyte infiltration in the liver.


Assuntos
Bifidobacterium breve , Regulação da Expressão Gênica , Lacticaseibacillus rhamnosus , Hepatopatias/metabolismo , Fígado/metabolismo , Macrófagos/metabolismo , Probióticos/farmacologia , Animais , Biomarcadores/metabolismo , Fígado/patologia , Hepatopatias/patologia , Macrófagos/patologia , Masculino , Ratos , Ratos Zucker
11.
J Mol Histol ; 52(1): 113-123, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33237375

RESUMO

The neuronal apoptosis inhibitory protein (NAIP) is a constituent of the NLRC4 inflammasome, which plays a key role in innate immunity, and an antiapoptotic protein. Recently, we reported the previously undescribed role of NAIP in cell division. The liver is one of the body's most actively regenerative organs. Given the novel mitotic role of NAIP, we examined its expression in hepatic mass restoration. The major liver lobe of Wistar rats was removed, and samples from both newly formed liver tissue, assessed by positive Ki67 immunostaining, and the remnant, intact liver lobes from hepatectomized rats were taken 3 and 7 days after surgery. Naip5 and Naip6 mRNA levels were significantly higher in regenerating hepatic tissue than in intact liver lobe tissue, and this increase was also observed at the protein level. Naip5 and Naip6 mRNA in situ hybridization showed that this increase occurred in the hepatic parenchyma. The histology of the regenerated liver tissue was normal, with the exception of a noticeable deficiency of hepatic lobule central veins. The results of this study suggest the involvement of NAIP in liver mass restoration following partial hepatectomy.


Assuntos
Fígado/anatomia & histologia , Fígado/metabolismo , Proteína Inibidora de Apoptose Neuronal/metabolismo , Animais , Divisão Celular , Linhagem Celular , Regulação da Expressão Gênica , Hepatócitos/citologia , Hepatócitos/metabolismo , Humanos , Regeneração Hepática/genética , Masculino , Modelos Animais , Proteína Inibidora de Apoptose Neuronal/genética , Tamanho do Órgão , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar
12.
Microorganisms ; 7(3)2019 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-30832423

RESUMO

Specific microbial profiles and changes in intestinal microbiota have been widely demonstrated to be associated with the pathogenesis of a number of extra-intestinal (obesity and metabolic syndrome) and intestinal (inflammatory bowel disease) diseases as well as other metabolic disorders, such as non-alcoholic fatty liver disease and type 2 diabetes. Thus, maintaining a healthy gut ecosystem could aid in avoiding the early onset and development of these diseases. Furthermore, it is mandatory to evaluate the alterations in the microbiota associated with pathophysiological conditions and how to counteract them to restore intestinal homeostasis. This review highlights and critically discusses recent literature focused on identifying changes in and developing gut microbiota-targeted interventions (probiotics, prebiotics, diet, and fecal microbiota transplantation, among others) for the above-mentioned pathologies. We also discuss future directions and promising approaches to counteract unhealthy alterations in the gut microbiota. Altogether, we conclude that research in this field is currently in its infancy, which may be due to the large number of factors that can elicit such alterations, the variety of related pathologies, and the heterogeneity of the population involved. Further research on the effects of probiotics, prebiotics, or fecal transplantations on the composition of the human gut microbiome is necessary.

13.
Nutrients ; 11(8)2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31370223

RESUMO

Previous studies have reported that probiotics may improve clinical and inflammatory parameters in patients with obesity and metabolic syndrome (MetS). Lactobacillus (L.) reuteri V3401 has shown promising results on the components of MetS in animal studies. We aimed to evaluate the effects of L. reuteri V3401 together with healthy lifestyle recommendations on adult patients with MetS. METHODS: We carried out a randomized, crossover, placebo-controlled, single-center trial in which we included 53 adult patients newly diagnosed with MetS. Patients were block randomly allocated by body mass index (BMI) and sex to receive a capsule containing either the probiotic L. reuteri V3401 (5 × 109 colony-forming units) or a placebo once daily for 12 weeks. Anthropometric variables, biochemical and inflammatory biomarkers, as well as the gastrointestinal microbiome composition were determined. RESULTS: There were no differences between groups in the clinical characteristics of MetS. However, we found that interleukin-6 (IL-6) and soluble vascular cell adhesion molecule 1 (sVCAM-1) diminished by effect of the treatment with L. reuteri V3401. Analysis of the gastrointestinal microbiome revealed a rise in the proportion of Verrucomicrobia. CONCLUSIONS: Consumption of L. reuteri V3401 improved selected inflammatory parameters and modified the gastrointestinal microbiome. Further studies are needed to ascertain additional beneficial effects of other probiotic strains in MetS as well as the mechanisms by which such effects are exerted.


Assuntos
Microbioma Gastrointestinal , Inflamação/metabolismo , Limosilactobacillus reuteri , Síndrome Metabólica/sangue , Síndrome Metabólica/terapia , Adulto , Biomarcadores/sangue , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Inflamação/sangue , Masculino , Síndrome Metabólica/metabolismo , Probióticos
14.
Cell Transplant ; 17(7): 845-57, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19044210

RESUMO

Cord blood is an attractive cell source in regenerative medicine and represents an alternative to bone marrow. The aim of this study was to investigate whether human umbilical cord blood mononuclear (HUCBM) cells might be valuable in hepatic regenerative medicine. HUCBM cells differentiated in vitro into hepatocytes, as suggested by expression of albumin, cytokeratin-18, glutamine synthetase, alpha-fetoprotein, and cytochrome P450 3A4 at both mRNA and protein levels in a time-dependent fashion. In contrast, the hematopoietic phenotype was gradually lost, as demonstrated by disappearance of CD45 expression. The regenerative potential of HUCBM cells was tested by using a human-to-rat xenotransplant model in which HUCBM cells were intraportally injected into rats with D-galactosamine-induced hepatitis. Liver histology and biochemical markers of hepatic damage were determined. Presence of human cells was detected in blood and liver of both control and D-galactosamine-treated animals. Cell transplantation produced an improvement in both the histological damage and liver function, as demonstrated by plasma values of alkaline phosphatase, gamma-glutamyl transferase, lactate dehydrogenase, and total and direct bilirubins. Results obtained suggest that HUCBM cells are capable of hepatic engraftment in this human-to-rat xenotransplant model and that transplantation of HUCBM cells may be a suitable therapy for liver disease.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/terapia , Sangue Fetal/citologia , Galactosamina/toxicidade , Leucócitos Mononucleares/transplante , Transplante Heterólogo , Animais , Biomarcadores/metabolismo , Células Cultivadas , Humanos , Leucócitos Mononucleares/citologia , Fígado/citologia , Fígado/metabolismo , Fígado/patologia , Masculino , Ratos , Ratos Wistar
15.
Nutrients ; 10(8)2018 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-30096792

RESUMO

Maternal milk contains compounds that may affect newborn immunity. Among these are a group of oligosaccharides that are synthesized in the mammary gland from lactose; these oligosaccharides have been termed human milk oligosaccharides (HMOs). The amount of HMOs present in human milk is greater than the amount of protein. In fact, HMOs are the third-most abundant solid component in maternal milk after lactose and lipids, and are thus considered to be key components. The importance of HMOs may be explained by their inhibitory effects on the adhesion of microorganisms to the intestinal mucosa, the growth of pathogens through the production of bacteriocins and organic acids, and the expression of genes that are involved in inflammation. This review begins with short descriptions of the basic structures of HMOs and the gut immune system, continues with the beneficial effects of HMOs shown in cell and animal studies, and it ends with the observational and randomized controlled trials carried out in humans to date, with particular emphasis on their effect on immune system development. HMOs seem to protect breastfed infants against microbial infections. The protective effect has been found to be exerted through cell signaling and cell-to-cell recognition events, enrichment of the protective gut microbiota, the modulation of microbial adhesion, and the invasion of the infant intestinal mucosa. In addition, infants fed formula supplemented with selected HMOs exhibit a pattern of inflammatory cytokines closer to that of exclusively breastfed infants. Unfortunately, the positive effects found in preclinical studies have not been substantiated in the few randomized, double-blinded, multicenter, controlled trials that are available, perhaps partly because these studies focus on aspects other than the immune response (e.g., growth, tolerance, and stool microbiota).


Assuntos
Aleitamento Materno , Sistema Imunitário/crescimento & desenvolvimento , Leite Humano/imunologia , Oligossacarídeos/imunologia , Animais , Desenvolvimento Infantil , Feminino , Microbioma Gastrointestinal/imunologia , Regulação da Expressão Gênica no Desenvolvimento , Interações Hospedeiro-Patógeno , Humanos , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido , Intestinos/crescimento & desenvolvimento , Intestinos/imunologia , Intestinos/microbiologia , Estado Nutricional
17.
Artigo em Inglês | MEDLINE | ID: mdl-30110974

RESUMO

The microorganisms that live symbiotically in human beings are increasingly recognized as important players in health and disease. The largest collection of these microorganisms is found in the gastrointestinal tract. Microbial composition reflects both genetic and lifestyle variables of the host. This microbiota is in a dynamic balance with the host, exerting local and distant effects. Microbial perturbation (dysbiosis) could contribute to the risk of developing health problems. Various bacterial genes capable of producing estrogen-metabolizing enzymes have been identified. Accordingly, gut microbiota is capable of modulating estrogen serum levels. Conversely, estrogen-like compounds may promote the proliferation of certain species of bacteria. Therefore, a crosstalk between microbiota and both endogenous hormones and estrogen-like compounds might synergize to provide protection from disease but also to increase the risk of developing hormone-related diseases. Recent research suggests that the microbiota of women with breast cancer differs from that of healthy women, indicating that certain bacteria may be associated with cancer development and with different responses to therapy. In this review, we discuss recent knowledge about the microbiome and breast cancer, identifying specific characteristics of the human microbiome that may serve to develop novel approaches for risk assessment, prevention and treatment for this disease.


Assuntos
Neoplasias da Mama/microbiologia , Microbiota/fisiologia , Disbiose , Estrogênios/biossíntese , Feminino , Microbioma Gastrointestinal/fisiologia , Humanos
18.
Motor Control ; 22(2): 170, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-28530475

RESUMO

Evaluation of muscular fatigue thresholds in athletes performing short-duration and explosive exercises is difficult because classic parameters do not suffer large variations. Therefore, the aim of this study was to develop a new method to estimate the fatigue threshold in single muscles. Our approach is based on electromyographic data recorded during a maximum incremental strength test until the one repetition maximum is reached. Ten men and 10 women performed a half-squat strength test consisting of five incremental intensities of one repetition maximum. Neither heart rate nor blood lactate concentrations showed significant differences at the various intensities tested. Surface electromyographic activities of vastus lateralis, vastus medialis, and rectus femoris were recorded, finding a break point corresponding to the fatigue threshold occurring in men at 70.74%, 71.48%, and 72.52% of one repetition maximum, respectively. In women, break-point values were 76.66% for vastus lateralis, 76.27% for vastus medialis, and 72.10% for rectus femoris. In conclusion, surface electromyography could be a useful, rapid, and noninvasive tool to determine the fatigue threshold of independent muscles during a maximal half-squat strength test.


Assuntos
Eletromiografia/métodos , Exercício Físico/fisiologia , Fadiga/diagnóstico , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
19.
Sci Data ; 4: 170186, 2017 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-29231922

RESUMO

We investigated whether the administration of Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036 modulate the expression of genes in the intestinal mucosa of obese Zucker rats. Forty-eight Zucker-Leprfa/fa and 16 Zucker lean Lepr+/fa rats were used. Eight Zucker lean Lepr+/fa and 8 Zucker-Leprfa/fa rats were euthanized as a reference. The remaining 40 Zucker-Leprfa/fa rats were then assigned to receive 1010 colony forming units (CFU) of one of the three probiotic strains, a mixture of L. paracasei CNCM I-4034 and B. breve CNCM I-4035, or a placebo by oral administration for 30 days. An additional group of 8 Zucker lean Lepr+/fa rats received the placebo for 30 days. Over 27,000 rat genes were studied using a DNA array. Four animals per group were used. Total RNA was extracted from intestinal mucosa and cDNA was synthesized, fragmented and labeled. Labeled cDNA was hybridized using GeneChip kits, and the latter were scanned. Intensity values of each probe were processed and normalized to obtain an individual value for each set of probes.


Assuntos
Mucosa Intestinal , Obesidade/genética , Animais , Perfilação da Expressão Gênica , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Obesidade/patologia , Probióticos/administração & dosagem , Ratos , Ratos Zucker
20.
Sci Rep ; 7(1): 1939, 2017 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-28512356

RESUMO

We have previously reported that administration of Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036 to obese Zucker-Lepr fa/fa rats attenuates liver steatosis and exerts anti-inflammatory effects. The goal of the present work was to investigate the modulation of gene expression in intestinal mucosa samples of obese Zucker-Lepr fa/fa rats fed the probiotic strains using a DNA microarray and postgenomic techniques. We also measured secretory IgA content in the gut and lipopolysaccharide (LPS)-binding protein (LBP) in serum. Expression of three genes (Adamdec1, Ednrb and Ptgs1/Cox1) was up-regulated in the intestinal mucosa of the obese rats compared with that in the rats when they were still lean. Probiotic administration down-regulated expression of Adamdec1 and Ednrb at the mRNA and protein levels and that of Ptgs1/Cox1 at the mRNA level, and this effect was in part mediated by a decrease in both macrophage and dendritic cell populations. Probiotic treatment also increased secretory IgA content and diminished the LBP concentration. Based on results reported in this work and else where, we propose a possible mechanism of action for these bacterial strains.


Assuntos
Proteínas ADAM/genética , Ciclo-Oxigenase 1/genética , Enterite/etiologia , Microbioma Gastrointestinal , Mucosa Intestinal/metabolismo , Proteínas de Membrana/genética , Probióticos , Receptor de Endotelina B/genética , Animais , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Expressão Gênica , Mucosa Intestinal/patologia , Macrófagos/imunologia , Macrófagos/metabolismo , Obesidade , Fenótipo , Ratos , Ratos Zucker
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