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1.
Microbiome ; 9(1): 55, 2021 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-33622394

RESUMO

BACKGROUND: The intestinal microbiota plays a crucial role in protecting the host from pathogenic microbes, modulating immunity and regulating metabolic processes. We studied the simplified human intestinal microbiota (SIHUMIx) consisting of eight bacterial species with a particular focus on the discovery of novel small proteins with less than 100 amino acids (= sProteins), some of which may contribute to shape the simplified human intestinal microbiota. Although sProteins carry out a wide range of important functions, they are still often missed in genome annotations, and little is known about their structure and function in individual microbes and especially in microbial communities. RESULTS: We created a multi-species integrated proteogenomics search database (iPtgxDB) to enable a comprehensive identification of novel sProteins. Six of the eight SIHUMIx species, for which no complete genomes were available, were sequenced and de novo assembled. Several proteomics approaches including two earlier optimized sProtein enrichment strategies were applied to specifically increase the chances for novel sProtein discovery. The search of tandem mass spectrometry (MS/MS) data against the multi-species iPtgxDB enabled the identification of 31 novel sProteins, of which the expression of 30 was supported by metatranscriptomics data. Using synthetic peptides, we were able to validate the expression of 25 novel sProteins. The comparison of sProtein expression in each single strain versus a multi-species community cultivation showed that six of these sProteins were only identified in the SIHUMIx community indicating a potentially important role of sProteins in the organization of microbial communities. Two of these novel sProteins have a potential antimicrobial function. Metabolic modelling revealed that a third sProtein is located in a genomic region encoding several enzymes relevant for the community metabolism within SIHUMIx. CONCLUSIONS: We outline an integrated experimental and bioinformatics workflow for the discovery of novel sProteins in a simplified intestinal model system that can be generically applied to other microbial communities. The further analysis of novel sProteins uniquely expressed in the SIHUMIx multi-species community is expected to enable new insights into the role of sProteins on the functionality of bacterial communities such as those of the human intestinal tract. Video abstract.


Assuntos
Proteínas de Bactérias/análise , Proteínas de Bactérias/química , Comunicação Celular , Microbioma Gastrointestinal , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Proteínas de Bactérias/genética , Microbioma Gastrointestinal/genética , Humanos , Intestinos/química , Intestinos/microbiologia , Metagenoma/genética , Espectrometria de Massas em Tandem
2.
Anal Chem ; 93(4): 2144-2151, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33470103

RESUMO

Local delivery to the lower gut to treat diseases of the colon has become a topic of special attention. Tissue exposure of locally acting agents is not represented by plasma concentrations. Therefore, reliable methods to measure tissue uptake at the primary site of action (e.g., epithelial layer or lamina propria) are vital. This work investigates the suitability of mass spectrometry imaging (MSI) in quantitatively visualizing intestinal transmural drug distribution. Tofacitinib (Tofa), a drug approved for the treatment of several autoimmune diseases, including ulcerative colitis, was selected as a tool compound for feasibility studies. One- and 7-h postdose sections of the ileum, proximal- and distal-colon from rats that received an oral solution of Tofa were subjected to matrix-assisted laser desorption ionization (MALDI)-MSI. A dilution series of individual concentrations sprayed over an entire tissue section allowed for tissue type-specific quantitation. At 1 h (systemic Tmax), the signal was highest in the ileum, whereas at 7 h, the signal was highest in the colon, when the unabsorbed fraction of the compound reached the colon. A combination of three-dimensional (3D) intensity plots and hematoxylin and eosin (H&E) stains showed a visually observable gradual decrease in Tofa concentration from the lumen toward the muscular layer of the proximal colon. The high luminal concentration of Tofa indicated that flushing of the intestines with saline does not result in complete removal of the drug material from the lumen. This could cause an overestimation of drug concentration in gut tissue homogenates by conventional liquid chromatography-mass spectrometry (LC-MS) methods. This study demonstrates the utility of MSI to differentiate between the lumen and intestinal wall layers and enables proper interpretation of tissue distribution data.


Assuntos
Intestinos/química , Espectrometria de Massas/métodos , Imagem Molecular/métodos , Piperidinas/administração & dosagem , Piperidinas/farmacocinética , Pirimidinas/administração & dosagem , Pirimidinas/farmacocinética , Administração Oral , Animais , Masculino , Piperidinas/química , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacocinética , Pirimidinas/química , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
3.
Methods Mol Biol ; 2194: 291-300, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32926372

RESUMO

Bile acids are important end products of cholesterol metabolism, having been shown to serve as signaling molecules and intermediates between the host and the gut microbiota. Here we describe a robust and accurate method using ultrahigh-pressure liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) for the quantification of bile acids in stool/cecal and tissue samples.


Assuntos
Ácidos e Sais Biliares/análise , Cromatografia Líquida de Alta Pressão/métodos , Metabolômica/métodos , Espectrometria de Massas em Tandem/métodos , Ácidos e Sais Biliares/sangue , Fezes/química , Intestinos/química , Fígado/química
4.
Ecotoxicol Environ Saf ; 202: 110913, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32800248

RESUMO

Soil is considered as a sink for heavy metals. Human health is severely affected by the continuous intake of toxic heavy metals even in a very low concentration. In the present experiment, we determined the influence of nutritional status including control (fasted condition), glucose (fed state), plant protein (fed state), animal protein (fed state) and calcium (fed state) on soil cadmium (Cd) and copper (Cu) bioaccessibility using physiologically-based extraction test (PBET) method together with simulator of the human intestinal microbial ecosystem (SHIME) model. The bioaccessibility of Cd was 1.06-73.58%, 0.44-54.79% and 0-17.78% and Cu was 3.81-67.32%, 4.98-71.14%, and 0-17.54% in the phase-I, phase-II and Phase-III respectively (in this study gastric phase, small intestinal phase and colon phase were considered as phase-I, phase-II and Phase-III respectively). The outcomes showed that, the average Cd bioaccessibility was higher with animal protein addition compared with other treatments in different phases. So, the effect of animal protein on Cd bioaccessibility was higher than other treatments in the phase-I, phase-II and phase-III. Due to the addition of plant protein, the higher average bioaccessibility of Cu was noticed in phase-I and phase-II in comparison to other treatments. However, in phase-III, the higher average bioaccessibility of Cu was found due to control treatment comparing with other treatments. Therefore, the influence of plant protein was higher than other nutrients on Cu bioaccessibility in the phase-I and phase-II. Moreover, other nutrients showed variable influence on Cd and Cu bioaccessibility. So, nutritional status has a significant effect on bioaccessibility as well as human health risk assessment.


Assuntos
Cádmio/análise , Cobre/análise , Poluentes do Solo/análise , Ecossistema , Monitoramento Ambiental/métodos , Poluição Ambiental , Humanos , Intestinos/química , Metais Pesados , Nutrientes , Solo
5.
Gastroenterol Hepatol ; 43(8): 464-471, 2020 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32859408

RESUMO

The SARS-CoV-2 pandemic is leading to high mortality and a global health crisis. The primary involvement is respiratory; however, the virus can also affect other organs, such as the gastrointestinal tract and liver. The most common symptoms are anorexia and diarrhea. In about half of the cases, viral RNA could be detected in the stool, which is another line of transmission and diagnosis. covid19 has a worse prognosis in patients with comorbidities, although there is not enough evidence in case of previous digestive diseases. Digestive endoscopies may give rise to aerosols, which make them techniques with a high risk of infection. Experts and scientific organizations worldwide have developed guidelines for preventive measures. The available evidence on gastrointestinal and hepatic involvement, the impact on patients with previous digestive diseases and operating guidelines for Endoscopy Units during the pandemic are reviewed.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/complicações , Doenças do Sistema Digestório/etiologia , Sistema Digestório/virologia , Pandemias , Pneumonia Viral/complicações , Aerossóis , Anorexia/etiologia , Antivirais/efeitos adversos , Betacoronavirus/isolamento & purificação , Betacoronavirus/fisiologia , Estudos de Coortes , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Diarreia/etiologia , Doenças do Sistema Digestório/virologia , Endoscopia do Sistema Digestório/efeitos adversos , Fezes/virologia , Humanos , Imunossupressores/efeitos adversos , Intestinos/química , Intestinos/virologia , Hepatopatias/etiologia , Estudos Multicêntricos como Assunto , Pandemias/prevenção & controle , Peptidil Dipeptidase A/análise , Peptidil Dipeptidase A/fisiologia , Equipamento de Proteção Individual , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão , Receptores Virais/análise , Receptores Virais/fisiologia , Risco , Precauções Universais
6.
J Food Sci ; 85(7): 1983-1987, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32572984

RESUMO

Because omega-3 fatty acids, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and their metabolites are known to possess anti-inflammatory and health-promoting functions in human and experimental animals, their intake is assumed to be beneficial for maintaining our health. We previously identified a cytochrome P450-metabolite of EPA, 5,6-dihydroxy-8Z,11Z,14Z,17Z-eicosatetraenoic acid (5,6-DiHETE), as a novel bioactive lipid, which inhibits vascular hyperpermeability in inflammation. Because blue back fishes including sardine, mackerel, and horse mackerel are reported to contain high concentrations of omega-3 fatty acids, we investigated which tissue of blue back fish is suitable as a source of 5,6-DiHETE. We measured the concentration of 5,6-DiHETE as well as major fatty acids in muscle, bone, heart, liver, and intestine of blue back fishes. Arachidonic acid was detected richer in intestines than other tissues of blue back fishes. The concentrations were between 4.45 and 5.62 µg/g tissue weight. EPA and DHA are also detected richer in intestines of blue back fishes. The concentrations were between 75.95 and 358.04 µg/g, and 203.09 and 464.88 µg/g, respectively. Especially, mackerel intestine contained the highest levels of both EPA and DHA. 5,6-DiHETE was present in greater amount in livers and intestines of blue back fishes. The livers contained 118.98 to 476.11 ng/g, whereas intestines contained 156.14 to 970.22 ng/g of 5,6-DiHETE. Of interest, sardine intestine contained much higher level of 5,6-DiHETE than the other fish tissues. These results suggest that visceral organs of blue back fishes, remarkably sardine intestine, can be a good source of 5,6-DiHETE. PRACTICAL APPLICATION: A novel anti-inflammatory lipid, 5,6-DiHETE, was detected in each tissues of blue back fishes. Especially their intestines contain the highest concentration of this lipid.


Assuntos
Anti-Inflamatórios/química , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/química , Peixes/metabolismo , Animais , Anti-Inflamatórios/metabolismo , Ácido Eicosapentaenoico/análise , Ácido Eicosapentaenoico/metabolismo , Mucosa Intestinal/metabolismo , Intestinos/química , Alimentos Marinhos/análise
7.
Carbohydr Polym ; 235: 115904, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32122473

RESUMO

In vitro digestive conditions were simulated to investigate the digestibility of polysaccharides prepared from squash (SPS). A small amount of free glucose monosaccharide was released after salivary and intestinal digestion due to the breakdown of α-(1 → 4)-glucose linkages and may form SPS or a starch impurity. At the same time, there was no obvious change in molecular weight distribution and reducing sugar content throughout this digestion period, demonstrating that the main structure of SPS was relatively stable under the simulated digestive conditions. Thus, most SPS can be transported intact to the large intestine. In addition, SPS alleviated type 2 diabetes (T2D) in rats. Moreover, the content of short-chain fatty acids (SCFAs) in the colon significantly increased after treatment with SPS. The present research provides insight into the non-digestibility of SPS, and suggests its utility to alleviate T2D by promoting the production of SCFA in the colon.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Ácidos Graxos Voláteis/biossíntese , Polissacarídeos/metabolismo , Animais , Colo/química , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Tipo 2/induzido quimicamente , Ácidos Graxos Voláteis/análise , Intestinos/química , Masculino , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Ratos , Ratos Wistar , Saliva/química , Saliva/metabolismo , Estômago/química , Estreptozocina/administração & dosagem
8.
Lab Invest ; 100(8): 1102-1110, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32203151

RESUMO

Biological materials presenting early signs of cancer would be beneficial for cancer screening/diagnosis. In this respect, the suitability of potentially exploiting mucus in colorectal cancer was tested using infrared spectroscopy in combination with statistical modeling. Twenty-six paraffinized colon tissue biopsy sections containing mucus regions from 20 individuals (10 normal and 16 cancerous) were measured using mid-infrared spectroscopic imaging. A digital de-paraffinization, followed by cluster analysis driven digital color-coded multi-staining segmented the infrared images into various histopathological features such as epithelium, connective tissue, stroma, and mucus regions within the tissue sections. Principal component analysis followed by supervised linear discriminant analysis was carried out on pure mucus and epithelial spectra from normal and cancerous regions of the tissue. For the mucus-based classification, a sensitivity of 96%, a specificity of 83%, and an area under the curve performance of 95% was obtained. For the epithelial tissue-based classification, a sensitivity of 72%, a specificity of 88%, and an area under the curve performance of 89% was obtained. The mucus spectral profiles further showed contributions indicative of glycans including that of sialic acid changes between these pathology groups. The study demonstrates that infrared spectroscopic analysis of mucus discriminates colorectal cancers with high sensitivity. This concept could be exploited to develop screening/diagnostic approaches complementary to histopathology.


Assuntos
Neoplasias do Colo/diagnóstico , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Muco/metabolismo , Espectrofotometria Infravermelho/métodos , Análise por Conglomerados , Colo/metabolismo , Colo/patologia , Neoplasias do Colo/metabolismo , Neoplasias Colorretais/metabolismo , Análise Discriminante , Humanos , Intestinos/química , Intestinos/patologia , Ácido N-Acetilneuramínico/metabolismo , Polissacarídeos/metabolismo , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
9.
Circ Res ; 126(7): 839-853, 2020 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-32078445

RESUMO

RATIONALE: High-salt diet is one of the most important risk factors for hypertension. Intestinal flora has been reported to be associated with high salt-induced hypertension (hSIH). However, the detailed roles of intestinal flora in hSIH pathogenesis have not yet been fully elucidated. OBJECTIVE: To reveal the roles and mechanisms of intestinal flora in hSIH development. METHODS AND RESULTS: The abovementioned issues were investigated using various techniques including 16S rRNA gene sequencing, untargeted metabolomics, selective bacterial culture, and fecal microbiota transplantation. We found that high-salt diet induced hypertension in Wistar rats. The fecal microbiota of healthy rats could dramatically lower blood pressure (BP) of hypertensive rats, whereas the fecal microbiota of hSIH rats had opposite effects. The composition, metabolism, and interrelationship of intestinal flora in hSIH rats were considerably reshaped, including the increased corticosterone level and reduced Bacteroides and arachidonic acid levels, which tightly correlated with BP. The serum corticosterone level was also significantly increased in rats with hSIH. Furthermore, the above abnormalities were confirmed in patients with hypertension. The intestinal Bacteroides fragilis could inhibit the production of intestinal-derived corticosterone induced by high-salt diet through its metabolite arachidonic acid. CONCLUSIONS: hSIH could be transferred by fecal microbiota transplantation, indicating the pivotal roles of intestinal flora in hSIH development. High-salt diet reduced the levels of B fragilis and arachidonic acid in the intestine, which increased intestinal-derived corticosterone production and corticosterone levels in serum and intestine, thereby promoting BP elevation. This study revealed a novel mechanism different from inflammation/immunity by which intestinal flora regulated BP, namely intestinal flora could modulate BP by affecting steroid hormone levels. These findings enriched the understanding of the function of intestinal flora and its effects on hypertension.


Assuntos
Pressão Sanguínea/fisiologia , Corticosterona/biossíntese , Microbioma Gastrointestinal/fisiologia , Hipertensão/fisiopatologia , Intestinos/química , Animais , Ácido Araquidônico/metabolismo , Bacteroides fragilis/fisiologia , Corticosterona/sangue , Transplante de Microbiota Fecal , Fezes/microbiologia , Humanos , Hipertensão/etiologia , Hipertensão/microbiologia , Intestinos/efeitos dos fármacos , Intestinos/microbiologia , Metabolômica/métodos , Ratos Wistar , Cloreto de Sódio na Dieta/efeitos adversos
10.
Environ Int ; 137: 105568, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32106047

RESUMO

Aflatoxin B1 (AFB1) is the most potent carcinogen among mycotoxins. Its biosynthesis involves the formation of versicolorin A (VerA), whose chemical structure shares many features with AFB1. Our data revealed significant levels of VerA in foodstuff from Central Asia and Africa. Given this emerging food risk, it was of prime interest to compare the toxic effects of the two mycotoxins against cells originating from the intestinal tract. We used human colon cell lines (Caco-2, HCT116) to investigate the cytotoxic process induced by the two mycotoxins. Contrary to AFB1, a low dose of VerA (1 µM) disturbed the expression level of thousands of genes (18 002 genes). We show that the cytotoxic effects of low doses of VerA (1-20 µM) were stronger than the same low doses of AFB1 in both Caco-2 and HCT116 cell lines. In Caco-2 cells, VerA induced DNA strand breaks that led to apoptosis and reduced DNA replication of dividing cells, consequently inhibiting cell proliferation. Although VerA was able to induce the p53 signaling pathway in p53 wild-type HCT116 cells, its toxicity process did not mainly rely on p53 expression since similar cytotoxic effects were also observed in HCT116 cells that do not express p53. In conclusion, this study provides evidence of the risk of food contamination by VerA and shed light on its toxicological effect on human colon cells.


Assuntos
Antraquinonas , Intestinos/química , Micotoxinas , Aflatoxina B1 , Antraquinonas/farmacocinética , Antraquinonas/toxicidade , Células CACO-2 , Carcinógenos , Humanos , Micotoxinas/farmacocinética , Micotoxinas/toxicidade
11.
Nanotechnology ; 31(19): 195102, 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31962292

RESUMO

Gold nanoparticles (AuNPs) are highly attractive to biomedical applications. Here, we investigated the effects of (i) ca. 15 nm spherical AuNPs capped with citrate or 11-mercaptoundecanoic acid (MUA) and (ii) ca. 60 nm spherical citrate-capped AuNPs, and ca. 60 nm MUA-capped star-shaped AuNPs on the cytotoxicity, cellular uptake and permeability, using media supplemented or not with 1% fetal bovine serum (FBS) on caucasian colon adenocarcinoma Caco-2 cells. In addition, the colloidal stability of the nanoparticles in media (supplemented or not) was assessed after 24 h-incubations at 60 µM. The 60 nm gold nanospheres and stars were administrated orally to Wistar rats in order to evaluate their systemic absorption and biodistribution after 24 h. At non-supplemented media settings, citrate-capped gold nanoparticles seem to be more toxic than their MUA-capped counterparts. Also, smaller nanoparticles show higher toxicity than larger ones. The use of cell culture media with 1% FBS not only increased the stability of all AuNPs, as also significantly reduced their cytotoxicity. In the uptake studies, higher AuNPs incorporation was noticed in serum supplemented media, this effect being particularly significant for the 60 nm nanoparticles. Cellular incorporation depended also on the capping agent and size. None of the tested samples crossed the in vitro intestinal barrier. Confirming the in vitro results, the in vivo biodistribution study of the 60 nm AuNPs orally given to rats showed that their systemic absorption is low and that they are mainly eliminated through the faeces. Altogether, these preliminary results suggest that our novel AuNPs have high potential to be considered promising candidates for application in diagnostics or drug delivery at the intestinal level, showing high biocompatibility. However, unless it is desired that these nanomaterials avoid systemic absorption upon oral administration, additional functionalization should be sought to increase their low bioavailability.


Assuntos
Ouro/administração & dosagem , Intestinos/química , Intestinos/citologia , Administração Oral , Animais , Células CACO-2 , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ácido Cítrico/química , Ouro/química , Ouro/farmacocinética , Humanos , Intestinos/efeitos dos fármacos , Nanopartículas Metálicas , Tamanho da Partícula , Permeabilidade , Ratos , Ratos Wistar , Distribuição Tecidual
12.
Int J Mol Sci ; 21(2)2020 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-31963640

RESUMO

The transition from pregnancy to lactation is characterized by a progressive decrease in insulin sensitivity. Propionate increases with dietary fiber consumption and has been shown to improve insulin sensitivity. Recent studies suggest that plasma odd-chain fatty acids [OCFAs; pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0)] that inversely correlated with insulin resistance are synthesized endogenously from gut-derived propionate. The present study investigated the effects of soluble fiber during gestation on gut microbiota, plasma non-esterified fatty acids and insulin sensitivity in sows. Sows were allocated to either control or 2.0% guar gum plus pregelatinized waxy maize starch (SF) dietary treatment during gestation. The SF addition changes the structure and composition of gut microbiota in sows. Genus Eubacterium increased by SF addition may promote intestinal propionate production. Moreover, the dietary SF increased circulating levels of plasma OCFAs, especially C17:0. The SF-fed sows had a higher insulin sensitivity and a lower systemic inflammation level during perinatal period. Furthermore, the plasma C15:0 and C17:0 was negatively correlated with the area under curve of plasma glucose after meal and plasma interleukin-6. In conclusion, dietary SF improves insulin sensitivity and alleviates systemic inflammation in perinatal sows, potentially related to its stimulating effect on propionate and OCFAs production.


Assuntos
Fibras na Dieta/administração & dosagem , Eubacterium/isolamento & purificação , Ácidos Graxos/sangue , Microbioma Gastrointestinal/efeitos dos fármacos , Propionatos/sangue , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Eubacterium/efeitos dos fármacos , Feminino , Galactanos/administração & dosagem , Gelatina/química , Resistência à Insulina , Intestinos/química , Intestinos/efeitos dos fármacos , Intestinos/microbiologia , Mananas/administração & dosagem , Gomas Vegetais/administração & dosagem , Gravidez , Suínos
13.
Ecotoxicol Environ Saf ; 190: 110130, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31918252

RESUMO

Environmental pollutants like methylmercury (MeHg) can bring devastating neurotoxicity to animals and human beings. Gut microbiota has been found to demethylate MeHg and promote the excretion of Hg through feces. However, the impacts of MeHg on gut microbiota and metabolites related to gut-brain interactions were less studied in mammals. The object of this study was to investigate the impacts of acute MeHg exposure on gut microbiome and metabolites together with its impact on gut integrity and related biological responses in rats. Rats were exposed to MeHg through oral administration and were sacrificed after 24 h 16 S rRNA gene sequencing was used to study the perturbance to gut microbiome and liquid chromatography mass spectrometry (LC-MS) was used for metabolomics profiling. It was found that gut was one of the target tissues of MeHg. MeHg induce the changes of intestinal microbial community structure and induce the regulating neuron activity change of intestinal neurotransmitters and metabolites on intestinal neurotransmitters and metabolites regulating the neuron activity. This was supported by the increased BDNF level. These findings may suggest a potential new mechanism regarding the neurotoxicity of MeHg. The protocols used in this study may also be applied to understand the neurotoxicity of other environmental neurotoxins like Pb, Mn, polychlorinated biphenyls, and pesticides, etc and to screen the neurotoxicity of emerging environmental contaminants.


Assuntos
Poluentes Ambientais/toxicidade , Microbioma Gastrointestinal/fisiologia , Compostos de Metilmercúrio/toxicidade , Testes de Toxicidade Aguda , Animais , Encéfalo , Cromatografia Líquida , Poluentes Ambientais/análise , Fezes/química , Microbioma Gastrointestinal/genética , Humanos , Hidrocarbonetos Aromáticos/análise , Intestinos/química , Masculino , Espectrometria de Massas/métodos , Mercúrio/análise , Metabolômica/métodos , Microbiota , Praguicidas/análise , Bifenilos Policlorados/análise , Ratos
14.
Colloids Surf B Biointerfaces ; 186: 110740, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31869603

RESUMO

Nanoemulsions are vesicular systems with great potential for the delivery of drugs, which significantly depends on the appropriate selection of the components that constitute them. In this sense, the use of materials with adequate toxicity profiles for the oral route provides additional advantages in terms of safety concerns avoidance. This work describes the formulation of novel two-component nanoemulsions constituted by α-tocopherol and ascorbyl-palmitate derivatives. Among them, ascorbyl-dipalmitate allowed the formation of nanoemulsions with size values around 170 nm and negative charge; additionally, they showed strong antioxidant capacity. These nanoemulsions are proposed to the oral route, so their behaviour in intestinal conditions was evaluated by incubating the nanoemulsion in simulated intestinal fluid. This process led to the formation of an intestinal-protein corona (I-PC) at the colloidal surface that determined the interaction with the mucus barrier. The I-PC displaced the immobile-hindered particles towards a subdiffusive-diffusive population. These studies report for the first time the effect of the I-PC on the mucodiffusion behaviour of vesicular systems, a finding that may help to comprehend the performance of nanocarriers under intestinal conditions.


Assuntos
Ácido Ascórbico/análogos & derivados , Intestinos/química , Nanopartículas/química , Coroa de Proteína/química , Ácido Ascórbico/química , Difusão , Emulsões/química , Tamanho da Partícula , Propriedades de Superfície , alfa-Tocoferol/química
15.
J Chem Ecol ; 45(11-12): 901-913, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31773376

RESUMO

Trail pheromones deposited by ants lead nestmates to food sources. Based on previous evidence that the trail pheromone of the carpenter ant Camponotus modoc originates from the hindgut, our objective in this study was to identify the key component(s) of the pheromone. We collected C. modoc colonies from conifer forests and maintained them in an outdoor enclosure near our laboratory for chemical analyses and behavioral experiments. In gas chromatographic-electroantennographic detection and gas chromatography-mass spectrometric analyses of worker ant hindgut extracts, we identified five candidate components: 2,4-dimethylhexanoic acid, 2,4-dimethyl-5-hexanolide, pentadecane, dodecanoic acid and 3,4-dihydro-8-hydroxy-3,5,7-trimethylisocoumarin. In a series of trail-following experiments, ants followed trails of synthetic 2,4-dimethyl-5-hexanolide, a blend of the five compounds, and hindgut extract over similar distances, indicating that the hexanolide accounted for the entire behavioral activity of the hindgut extract. The hexanolide not only mediated orientation of C. modoc foragers on trails, it also attracted them over distance, indicating a dual function. Further analyses and bioassays with racemic and stereoselectively synthesized hexanolides revealed that the ants produce, and respond to, the (2S,4R,5S)-stereoisomer. The same stereoisomer is a trail pheromone component in several Camponotus congeners, indicating significant overlap in their respective trail pheromone communication systems.


Assuntos
Misturas Complexas/análise , Feromônios/análise , Alcanos/análise , Animais , Formigas , Comportamento Animal , Técnicas Biossensoriais/métodos , Caproatos/análise , Cumarínicos/análise , Glândulas Exócrinas/metabolismo , Cromatografia Gasosa-Espectrometria de Massas/métodos , Intestinos/química , Ácidos Láuricos/análise , Estereoisomerismo
16.
Sci Rep ; 9(1): 14042, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31575982

RESUMO

V565 is an engineered TNFα-neutralising single domain antibody formulated into enteric coated mini-tablets to enable release in the intestine after oral administration as a possible oral treatment for inflammatory bowel disease (IBD). Following oral administration, ileal recovery of V565 was investigated in four patients with terminal ileostomy. Intestinal and systemic pharmacokinetics were measured in six patients with Crohn's disease and evidence of target engagement assessed in five patients with ulcerative colitis. Following oral administration, V565 was detected at micromolar concentrations in ileal fluid from the ileostomy patients and in stools of the Crohn's patients. In four of the five ulcerative colitis patients, biopsies taken after 7d dosing demonstrated V565 in the lamina propria with co-immunostaining on CD3+ T-lymphocytes and CD14+ macrophages. Phosphorylation of signalling proteins in biopsies taken after 7d oral dosing was decreased by approximately 50%. In conclusion, enteric coating of V565 mini-tablets provided protection in the stomach with gradual release in intestinal regions affected by IBD. Immunostaining revealed V565 tissue penetration and association with inflammatory cells, while decreased phosphoproteins after 7d oral dosing was consistent with V565-TNFα engagement and neutralising activity. Overall these results are encouraging for the clinical utility of V565 in the treatment of IBD.


Assuntos
Anticorpos/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Imunoterapia/métodos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Idoso , Anticorpos/análise , Anticorpos/metabolismo , Feminino , Humanos , Intestinos/química , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/uso terapêutico , Fator de Necrose Tumoral alfa/imunologia
17.
Medicina (Kaunas) ; 55(9)2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31480453

RESUMO

Background and Objectives: The morphopathogenesis of adhesions is a complex process, characterized by the accumulation of an extracellular matrix, inflammation and hypoxia. The regulatory role between morphopathogenic factors in adhesions has not yet been defined. The aim was to investigate the appearance of transforming growth factor beta (TGFß), hepatocyte growth factor (HGF), basic fibroblast growth factor (FGF-2), fibroblast growth factor receptor 1 (FGFR1), vascular endothelial growth factor (VEGF), protein gene product 9.5 (PGP 9.5), chromogranin A (CgA), interleukin-1 alpha (IL-1α), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-7 (IL-7), interleukin-8 (IL-8), interleukin-10 (IL-10), tumor necrosis factor alpha (TNFα), human beta defensine-2 (HBD-2), matrix metaloproteinase-2 (MMP-2) and matrix metaloproteinase-2 tissue inhibitor (TIMP-2) in intraabdominal adhesions. Materials and Methods: The study material was obtained from 49 patients under one year of age with total or partial bowel obstruction. All factors were detected using immunohistochemistry methods and their relative distribution was evaluated by means of the semiquantitative counting method. Results: Intraabdominal adhesions are characterized by increased TGFß, FGFR1, VEGF and decreased FGF-2, HGF, PGP 9.5, IL-1, IL-4, IL-8, TIMP-2 findings. The most significant changes observed were the remodulation of the extracellular matrix, promotion of neoangiogenesis and the maintenance of a prolonged inflammation. Conclusions: The increase in TGFß, relative to the decrease of HGF, as well as the disbalance between MMP-2 and TIMP-2 proves an increased fibrosis in intraabdominal adhesions. Less detected FGF-2 and more prominent FGR1 findings points out a compensatory receptor stimulation in response to the lacking same factor. The decrease in PGP 9.5 and the increase in VEGF-positive macrophages indicate hypoxic injury and proves the stimulation of neoangiogenesis. An unpronounced IL-1 and marked IL-10 finding indicate the local tissue protection reaction, the decrease in IL-4 could be the direct cause of giant cells, but the decrease of IL-8 could confirm a delayed chemotaxis of inflammatory cells.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Obstrução Intestinal/patologia , Aderências Teciduais/patologia , Humanos , Lactente , Peptídeos e Proteínas de Sinalização Intercelular/análise , Obstrução Intestinal/etiologia , Intestinos/química , Intestinos/patologia , Aderências Teciduais/etiologia
18.
Bull Environ Contam Toxicol ; 103(5): 670-675, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31471657

RESUMO

Here we evaluate the potential of heavy metal accumulation of Proteocephalus macrophallus parasitizing the Butterfly Peacock Bass (Cichla ocellaris). A total of 19 fish specimens were collected. From the hosts, samples of intestine, liver, muscle, and parasites were taken. Heavy metal concentrations (Al, As, Ba, Cd, Cr, Fe, Hg, Mg, Mn, Ni, Pb, Ti, and Zn) were obtained using Atomic Absorption Spectrometry. All analyzed elements was found in higher concentrations in the parasites comparing to its host tissues. The bioconcentration factors were higher in the intestine, varying between 5.91 (Ti) to 8.00 (Ba), followed by the muscle, 1.88 (Mg) to 6.39 (Zn), and liver, 1.67 (Al) to 2.02 (Ba). These results show that at the infection site heavy metal concentrations are reduced, since the elements are absorbed directly from the intestinal wall by the parasites. In general, P. macrophallus presents a reasonable capacity of metal accumulation comparing to its hosts.


Assuntos
Cestoides/metabolismo , Ciclídeos/parasitologia , Monitoramento Ambiental/métodos , Intestinos/química , Metais Pesados/análise , Poluentes Químicos da Água/análise , Animais , Brasil , Cestoides/isolamento & purificação , Alimentos Marinhos/análise
19.
J Am Soc Mass Spectrom ; 30(10): 2041-2050, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31385259

RESUMO

This paper reports matrix-assisted laser desorption/ionization mass spectrometry imaging to investigate systematic effects of a lentil extract treatment to lower cholesterol levels. For this purpose, mass spectrometry imaging was used to spatially investigate modifications in the lipid composition and cholesterol levels in the brain, liver, and intestines as well as bile acids in the liver and intestine of rats treated with lentil extract. Neither the lipid composition nor cholesterol levels in the brain samples were found to be significantly different between the treated and not-treated animal groups. The hypercholesterolemic livers showed signs of steatosis (lipid marker PG 36:4), but no modifications in bile acid, cholesterol, and lipid composition. We found significant differences (AUC > 0.75) in the intestines regarding bile acid and lipid composition after treatment with the lentil extract. The treated rats showed a decreased reabsorption (increased excretion) of ursodeoxycholic acid, deoxycholic acid, and chenodeoxycholic acid and an increased deconjugation of taurine-conjugated bile acids (taurochenodeoxycholic acid, taurodeoxycholic acid, taurocholic acid, and 3-keto-taurocholic acid). This indicates that the lentil extract lowers the total cholesterol level in two synergic ways: (i) it increases the excretion of bile acids; hence, new bile acids are produced in the liver from serum cholesterol and (ii) the prebiotic effect leads to free taurine which upregulates the de novo synthesis of bile acid from cholesterol while activating LDL receptors. We demonstrate here that mass spectrometry imaging is a valuable tool for a better understanding of the effects of treatments such as for the synergistic cholesterol-lowering effect of the lentil extract.


Assuntos
Anticolesterolemiantes/farmacologia , Ácidos e Sais Biliares/análise , Lipídeos/análise , Extratos Vegetais/farmacologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Animais , Ácidos e Sais Biliares/química , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Química Encefálica/efeitos dos fármacos , Colesterol/análise , Colesterol/química , Intestinos/química , Intestinos/diagnóstico por imagem , Intestinos/efeitos dos fármacos , Lens (Planta) , Lipídeos/química , Fígado/química , Fígado/diagnóstico por imagem , Fígado/efeitos dos fármacos , Masculino , Imagem Molecular , Ratos , Ratos Sprague-Dawley
20.
Mar Pollut Bull ; 146: 349-354, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31426167

RESUMO

Between 2012 and 2015, 13 grey seals were recovered from trammel nets targeting monkfish and rays off the south coast of Ireland. Incidence and distribution of microplastics were investigated along the intestines of bycaught seals. No macrodebris items were found, whereas microplastics were detected in all seals. A total of 363 microplastics items were identified (85% fibers, 14% fragments, 1% films). Estimation of microplastic ingestion based on prey ingestion (245 particles) was lower than the observed data. Acantocephala parasites (n = 1543) were found in 12 seals, with an average of 74.5 ±â€¯67.7 parasites per seal. Distribution of microplastics varied between seals, although microplastics tended to accumulate in areas where more parasites were aggregated; however, there was no significant relationship between the number of parasites and microplastics was found. Seals recovered from nets appear to be a good source to monitor the incidence of microplastic pollution within the coastal food webs.


Assuntos
Monitoramento Ambiental/métodos , Intestinos , Plásticos/análise , Focas Verdadeiras , Poluentes Químicos da Água/análise , Animais , Cadeia Alimentar , Conteúdo Gastrointestinal/química , Conteúdo Gastrointestinal/parasitologia , Intestinos/química , Intestinos/parasitologia , Irlanda , Parasitos/isolamento & purificação
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