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1.
Food Chem ; 370: 130980, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34628238

RESUMO

Low bioavailability currently limits the potential of curcumin as a health-promoting dietary compound. This study therefore explored the potential of excipient emulsions to improve curcumin bioavailability. Oil-in-water excipient emulsions were prepared using different types of oils: corn oil, olive oil, and medium chain triglycerides (MCT). The excipient emulsions increased the transportation rate of curcumin across the Caco-2 cell monolayer and showed ability to protect curcumin from metabolism in the enterocytes, with the olive oil-based systems exhibiting the highest efficacy. In addition, most of curcumin metabolites were present as hexahydro-curcumin (HHC) and its conjugates. Our results show that excipient emulsions can improve curcumin bioavailability by increasing its trans-enterocyte absorption and reducing cellular metabolism. Moreover, they show that these effects depend on the type of oil used to produce them. These findings have important implications for the rational design of lipid-based delivery systems to enhance the bioavailability of hydrophobic nutraceuticals like curcumin.


Assuntos
Curcumina , Excipientes , Disponibilidade Biológica , Células CACO-2 , Óleo de Milho , Curcumina/metabolismo , Emulsões/metabolismo , Excipientes/metabolismo , Trato Gastrointestinal/metabolismo , Humanos
2.
Int J Mol Sci ; 22(19)2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34639136

RESUMO

BACKGROUND: α-cyclodextrin (α-CD) is one of the dietary fibers that may have a beneficial effect on cholesterol and/or glucose metabolism, but its efficacy and mode of action remain unclear. METHODS: In the present study, we examined the anti-hyperglycemic effect of α-CD after oral loading of glucose and liquid meal in mice. RESULTS: Administration of 2 g/kg α-CD suppressed hyperglycemia after glucose loading, which was associated with increased glucagon-like peptide 1 (GLP-1) secretion and enhanced hepatic glucose sequestration. By contrast, 1 g/kg α-CD similarly suppressed hyperglycemia, but without increasing secretions of GLP-1 and insulin. Furthermore, oral α-CD administration disrupts lipid micelle formation through its inclusion of lecithin in the gut luminal fluid. Importantly, prior inclusion of α-CD with lecithin in vitro nullified the anti-hyperglycemic effect of α-CD in vivo, which was associated with increased intestinal mRNA expressions of SREBP2-target genes (Ldlr, Hmgcr, Pcsk9, and Srebp2). CONCLUSIONS: α-CD elicits its anti-hyperglycemic effect after glucose loading by inducing lecithin inclusion in the gut lumen and activating SREBP2, which is known to induce cholecystokinin secretion to suppress hepatic glucose production via a gut/brain/liver axis.


Assuntos
Trato Gastrointestinal/metabolismo , Hiperglicemia/prevenção & controle , Lecitinas/metabolismo , Período Pós-Prandial , Canais de Potássio Corretores do Fluxo de Internalização/fisiologia , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , alfa-Ciclodextrinas/farmacologia , Animais , Trato Gastrointestinal/efeitos dos fármacos , Hiperglicemia/etiologia , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína de Ligação a Elemento Regulador de Esterol 2/genética
3.
Nutrients ; 13(10)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34684436

RESUMO

Metabolic-associated fatty liver disease is a major cause of chronic pathologies, of which maternal obesity is a frequent risk factor. Gut wall and microbiota, visceral fat, and liver form a pre-systemic network for substrates and pro-inflammatory factors entering the body, undergoing accelerated maturation in early-life when the weaning reaction, i.e., a transitory inflammatory condition, affects lifelong health. We aimed to characterize organ metabolism in the above network, in relation to weaning reaction and maternal obesity. Weaning or 6-months-old offspring of high-fat-diet and normal-diet fed dams underwent in vivo imaging of pre-/post-systemic glucose uptake and tissue radiodensity in the liver, visceral fat, and intestine, a liver histology, and microbiota and metabolic pathway analyses. Weaning mice showed the dominance of gut Clostridia and Bacteroidia members, overexpressing pathways of tissue replication and inflammation; adulthood increased proneness to steatohepatitis, and Desulfovibrio and RF39 bacteria, and lipopolysaccharide, bile acid, glycosaminoglycan, and sphingolipid metabolic pathways. In vivo imaging could track organ maturation, liver inflammation, and protective responses. A maternal high-fat diet amplified the weaning reaction, elevating liver glucose uptake, triglyceride levels, and steatohepatitis susceptibility along the lifespan. The visceral network establishes a balance between metabolism and inflammation, with clear imaging biomarkers, and crucial modulation in the weaning time window.


Assuntos
Tecido Adiposo/metabolismo , Dieta Hiperlipídica , Retroalimentação Fisiológica , Trato Gastrointestinal/metabolismo , Fígado/metabolismo , Fenômenos Fisiológicos da Nutrição Materna , Efeitos Tardios da Exposição Pré-Natal , Desmame , Fatores Etários , Animais , Biomarcadores , Suscetibilidade a Doenças , Metabolismo Energético , Feminino , Microbioma Gastrointestinal , Imuno-Histoquímica , Redes e Vias Metabólicas , Camundongos , Especificidade de Órgãos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Gravidez
4.
Nutrients ; 13(10)2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34684585

RESUMO

Adipokines and gastrointestinal tract hormones are important metabolic parameters, and both epigenetic factors and differential gene expression patterns may be associated with the alterations in their concentrations in children. The function of the FTO gene (FTO alpha-ketoglutarate dependent dioxygenase) in the regulation of the global metabolic rate is well described, whereas the influence of protooncogene PLAG1 (PLAG1 zinc finger) is still not fully understood. A cross-sectional study on a group of 26 children with various BMI values (15.3-41.7; median 28) was carried out. The aim was to evaluate the dependencies between the level of methylation and expression of aforementioned genes with the concentration of selected gastrointestinal tract hormones and adipokines in children. Expression and methylation were measured in peripheral blood mononuclear DNA by a microarray technique and a restriction enzyme method, respectively. All peptide concentrations were determined using the enzyme immunoassay method. The expression level of both FTO and PLAG1 genes was statistically significantly related to the concentration of adipokines: negatively for apelin and leptin receptor, and positively for leptin. Furthermore, both FTO methylation and expression negatively correlated with the concentration of resistin and visfatin. Cholecystokinin was negatively correlated, whereas fibroblast growth factor 21 positively correlated with methylation and expression of the FTO gene, while FTO and PLAG1 expression was negatively associated with the level of cholecystokinin and glucagon-like peptide-1. The PLAG1 gene expression predicts an increase in leptin and decrease in ghrelin levels. Our results indicate that the FTO gene correlates with the concentration of hormones produced by the adipose tissue and gastrointestinal tract, and PLAG1 gene may be involved in adiposity pathogenesis. However, the exact molecular mechanisms still need to be clarified.


Assuntos
Adipocinas/sangue , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Metilação de DNA/genética , Proteínas de Ligação a DNA/genética , Trato Gastrointestinal/metabolismo , Regulação da Expressão Gênica , Peptídeos/sangue , Adolescente , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Criança , Proteínas de Ligação a DNA/metabolismo , Feminino , Humanos , Modelos Lineares , Masculino , Modelos Biológicos , Estatísticas não Paramétricas
5.
J Hazard Mater ; 416: 125899, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492837

RESUMO

Incidental oral ingestion is considered to be an important exposure route for humans to soil contaminants, such as fluoride (F). For 25 soil samples containing 4000 mg F/kg from aluminium smelting site in southwestern China, this study investigated F bioaccessibility in the human gastrointestinal tract in vitro. Fluoride bioaccessibility (2.4-48.8%) in the gastric phase was primarily caused by the dissolution of F-Ca and F-Al compounds (assigned to residual phase), identified by X-ray photoelectron spectroscopy and sequential extraction. Following modification to the small intestinal phase, the variation in F bioaccessibility (2.5-38.8%) should be the result of concurrent processes, including the formation of F complexes and competitive adsorption, and inversely the precipitation of fluorite and surface adsorption of formed F-Al complexes. The colon incubation with human gut microbiota yielded a 1.3-fold increase in F bioaccessibility (3.9-45.7%), probably due to the dissolution of F bound to Fe (hydr)oxides. Bioaccessibility adjustment can reduce hazard quotient of fluoride, and non-carcinogenic risk for children should be noted that soil F intake contributed 21.7% on average, up to 76.6% of oral reference dose. This will result in better understanding of human health risk assessment associated with F exposures.


Assuntos
Alumínio , Poluentes do Solo , Alumínio/metabolismo , Alumínio/toxicidade , Disponibilidade Biológica , Criança , Fluoretos/toxicidade , Trato Gastrointestinal/metabolismo , Humanos , Medição de Risco , Solo , Poluentes do Solo/metabolismo
6.
J Hazard Mater ; 416: 126146, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492932

RESUMO

As worldwide edible fungi, Lentinula edodes and Agaricus bisporus accumulate both essential and harmful metals. Metal bioavailability is important for metal benefit-risk assessment. A full functional model of digestive tracts (including digestion, metabolism, and absorption) is established. Under the digestive tract functions, the bioaccessible and bioavailable metals are released from edible fungi and absorbed by intestinal tract, respectively. Based on bioavailable metal contents in the intestine, safe dosage and maximum consumption are 43.52 g/d and 248.7 g/d for Agaricus bisporu, 20.59/328.9 g/d (for males/ female) and 132.9 g/d for Lentinus edodes; V, Co, Ni, Cu, Zn, Se, Cr, Cd and Pb in Agaricus bisporus and Lentinula edodes are absorbed mainly in the large intestine; Fe is mainly absorbed in small intestine; edible fungi species-specificity in metal bioavailability is observed for As and Mn, which are mainly absorbed by small and large intestine for Agaricus bisporus and Lentinus edodes, respectively; and then metal toxicity on small and large intestine is disclosed. Metal benefit-risk is assessed by the content of monolayer liposome-extracted metal in the chyme from small and large intestine, which is controlled by the gastrointestinal functions, metal and edible fungi species.


Assuntos
Agaricus , Metais Pesados , Disponibilidade Biológica , Biomimética , Digestão , Monitoramento Ambiental , Feminino , Trato Gastrointestinal/metabolismo , Humanos , Metais Pesados/análise , Medição de Risco
7.
J Insect Physiol ; 134: 104309, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34496279

RESUMO

The adult Drosophila intestinal epithelium must be tightly regulated to maintain regeneration and homeostasis. The dysregulation of the regenerative capacity is frequently associated with intestinal diseases such as inflammation and tumorigenesis. Here, we showed that the G protein-coupled receptor Anchor maintains Drosophila adult midgut homeostasis by restricting Jun-N-terminal kinase (JNK) and Notch pathway activity. anchor inactivation resulted in aberrant JNK pathway activation, which led to excessive enteroblast (EB) production and premature enterocyte (EC) differentiation. In addition, increased Notch levels promoted premature EC differentiation following the loss of anchor. This defect induced by the loss of anchor ultimately caused sensitivity to stress or environmental challenge in adult flies. Taken together, our results demonstrate that the activity of anchor is essential to coordinate stem cell differentiation and proliferation to maintain intestinal homeostasis.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Homeostase/fisiologia , Receptores Acoplados a Proteínas G/metabolismo , Animais , Proliferação de Células , Drosophila melanogaster/citologia , Drosophila melanogaster/metabolismo , Drosophila melanogaster/fisiologia , Enterócitos , Trato Gastrointestinal/citologia , Trato Gastrointestinal/metabolismo , Sistema de Sinalização das MAP Quinases , Receptores Notch/metabolismo , Transdução de Sinais
8.
Int J Mol Sci ; 22(18)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34576215

RESUMO

Depressive disorder in childhood and adolescence is a highly prevalent mood disorder that tends to recur throughout life. Untreated mood disorders can adversely impact a patient's quality of life and cause socioeconomic loss. Thus, an accurate diagnosis and appropriate treatment is crucial. However, until now, diagnoses and treatments were conducted according to clinical symptoms. Objective and biological validation is lacking. This may result in a poor outcome for patients with depressive disorder. Research has been conducted to identify the biomarkers that are related to depressive disorder. Cumulative evidence has revealed that certain immunologic biomarkers including brain-derived neurotrophic factor (BDNF) and cytokines, gastrointestinal biomarkers, hormones, oxidative stress, and certain hypothalamus-pituitary axis biomarkers are associated with depressive disorder. This article reviews the biomarkers related to the diagnosis and treatment of pediatric depressive disorders. To date, clinical biomarker tests are not yet available for diagnosis or for the prediction of treatment prognosis. However, cytokines such as Interleukin-2, interferon-gamma, tumor necrosis factor-alpha, and BDNF have shown significant results in previous studies of pediatric depressive disorder. These biomarkers have the potential to be used for diagnosis, prognostic assessment, and group screening for those at high risk.


Assuntos
Biomarcadores/sangue , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/diagnóstico , Adolescente , Animais , Fator Neurotrófico Derivado do Encéfalo/sangue , Criança , Citocinas/sangue , Citocinas/metabolismo , Transtorno Depressivo Maior/genética , Trato Gastrointestinal/metabolismo , Hormônios/sangue , Humanos , Hipotálamo/metabolismo , Sistema Imunitário , Inflamação , Interferon gama/sangue , Interleucina-2/sangue , Aprendizado de Máquina , Neurônios/patologia , Estresse Oxidativo , Hipófise/metabolismo , Prognóstico , Qualidade de Vida , Fator de Necrose Tumoral alfa/sangue
9.
Int J Mol Sci ; 22(17)2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34502396

RESUMO

The monoamine serotonin, 5-hydroxytryptamine (5-HT), is a remarkable molecule with conserved production in prokaryotes and eukaryotes and a wide range of functions. In the gastrointestinal tract, enterochromaffin cells are the most important source for 5-HT production. Some intestinal bacterial species are also able to produce 5-HT. Besides its role as a neurotransmitter, 5-HT acts on immune cells to regulate their activation. Several lines of evidence indicate that intestinal 5-HT signaling is altered in patients with inflammatory bowel disease. In this review, we discuss the current knowledge on the production, secretion, and signaling of 5-HT in the intestine. We present an inventory of intestinal immune and epithelial cells that respond to 5-HT and describe the effects of these signaling processes on intestinal homeostasis. Further, we detail the mechanisms by which 5-HT could affect inflammatory bowel disease course and describe the effects of interventions that target intestinal 5-HT signaling.


Assuntos
Trato Gastrointestinal/metabolismo , Serotonina/metabolismo , Serotonina/fisiologia , Animais , Colite , Células Enterocromafins/metabolismo , Células Enterocromafins/fisiologia , Células Epiteliais/metabolismo , Trato Gastrointestinal/fisiologia , Homeostase/fisiologia , Humanos , Inflamação , Doenças Inflamatórias Intestinais , Mucosa Intestinal/metabolismo , Intestinos , Transdução de Sinais/efeitos dos fármacos
10.
Front Public Health ; 9: 710484, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34589462

RESUMO

Objective: The aim of the study was to assess the influence of electromagnetic fields with divergent physical properties on the prooxidative and antioxidative balances in homogenates of the tongue, salivary glands, esophagus, stomach, and small and large intestines of rats. Material and Methods: Forty rats were randomly divided into four equal groups, namely, a control group, a group exposed to low-frequency electromagnetic fields (LF-EMFs; frequency: 50 Hz; intensity: 10 kV/m; magnetic induction: 4.3 pT), a group exposed to radiofrequency electromagnetic fields (RF-EMFs) emitted by mobile phones (frequency: 900 MHz), and a group exposed simultaneously to LF-EMFs and RF-EMFs emitted by mobile phones. After 28 consecutive days of the experiment, the following pro- and antioxidative markers were assessed in the gastrointestinal tract homogenates: superoxide dismutase (SOD) and its two isoenzymes (Mn-SOD, Cu,Zn-SOD) catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), total antioxidative capacity (TAC), total oxidative status (TOS), and malondialdehyde (MDA). Results: In rats exposed to LF-EMFs, higher concentrations of the markers of prooxidant processes, MDA or TOS, were observed in the salivary glands, esophagus, and small intestine homogenates in comparison with the control group. Additionally, in the group of rats opposite to the control, antioxidant activity was observed. The main differences included a higher activity of Cu,Zn-SOD in homogenates of the tongue, salivary glands, and esophagus as well as decreased activity of CAT in homogenates of the tongue, esophagus, and small intestine. In animals exposed to RF-EMFs, the concentration of TOS was higher in the large intestine than in control rats. The main difference of antioxidant activity was presented by decreased Cu,Zn-SOD in homogenates of the salivary glands, stomach, small and large intestine as well as CAT in homogenates of the tongue, esophagus, stomach, and small and large intestine. Moreover, in rats exposed simultaneously to LF-EMFs and RF-EMFs, a lower concentration of TOS was observed. Antioxidant activity was presented by a decreased activity of CAT in homogenates of the tongue, esophagus, stomach, and small and large intestine in comparison to the control group. Conclusion: Among those applied in the study, electromagnetic fields of a low-frequency caused the most significant disturbances of oxidative stress in the rat gastrointestinal tract.


Assuntos
Campos Eletromagnéticos , Estresse Oxidativo , Animais , Catalase/metabolismo , Campos Eletromagnéticos/efeitos adversos , Trato Gastrointestinal/metabolismo , Oxirredução , Ratos
11.
Front Immunol ; 12: 668974, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539623

RESUMO

Objectives: This aim of this study was to determine whether neutrophil extracellular traps (NETs) are involved in the pathogenesis of IgA vasculitis (IgAV) and investigate whether the circulating NETs levels are associated with disease activity in children. Methods: We performed a case-control study and collected blood samples from 193 children with different stages of IgAV (61 were at the onset stage, 64 at the remission stage, 43 at the active stage, and 25 were undergoing drug withdrawal). A total of 192 healthy children were recruited as controls. Circulating cell free DNA (cf-DNA) was obtained from the plasma and quantified by using the Quant-iT PicoGreen DNA quantification kit. NETs-associated myeloperoxidase-DNA (MPO-DNA), citrullinated-histone H3 (cit-H3), neutrophil elastase (NE), and the deoxyribonuclease I (DNase I) concentrations were measured using enzyme-linked immunosorbent assays. The presence of NETs in the kidney and gastrointestinal tissues of onset and active IgAV patients was determined by multiple immunofluorescence staining in 15 IgAV nephritis patients and 9 IgAV patients without IgAV nephritis, respectively. NETs degradation potency of collected sera samples from IgAV patients were checked in vitro. Relationships between circulating levels of cf-DNA with MPO-DNA, NE, and DNase I and the patients were analyzed. Results: Circulating levels of cf-DNA in onset and active IgAV patients were significantly higher than those in remission and drug withdrawal patients as well as healthy controls. The results were similar for MPO-DNA and NE. The levels of circulating cf-DNA correlated significantly with MPO-DNA, NE and DNase I. A significantly decreased degradation of NETs from the onset and active IgAV patients was observed, but was normal in healthy controls. Furthermore, presence of NETs was also confirmed in all renal and gastrointestinal tissues obtained from the onset and active IgAV patients but not control samples. Conclusions: Our data showed that NETs were released into the circulation of IgAV patients and are involved in the disease activity. The circulating levels of NETs maybe used to assess disease severity in children with IgAV.


Assuntos
Armadilhas Extracelulares/metabolismo , Imunoglobulina A/sangue , Neutrófilos/metabolismo , Púrpura de Schoenlein-Henoch/imunologia , Biomarcadores/sangue , Estudos de Casos e Controles , Ácidos Nucleicos Livres/sangue , Criança , Pré-Escolar , DNA/sangue , Feminino , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/metabolismo , Humanos , Rim/imunologia , Rim/metabolismo , Masculino , Ativação de Neutrófilo , Neutrófilos/imunologia , Púrpura de Schoenlein-Henoch/sangue , Púrpura de Schoenlein-Henoch/diagnóstico , Púrpura de Schoenlein-Henoch/tratamento farmacológico , Índice de Gravidade de Doença
12.
Int J Mol Sci ; 22(18)2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34575911

RESUMO

Schizophrenia is a severe neuropsychiatric disorder, and its etiology remains largely unknown. Environmental factors have been reported to play roles in the pathogenesis of schizophrenia, and one of the major environmental factors identified for this disorder is psychosocial stress. Several studies have suggested that stressful life events, as well as the chronic social stress associated with city life, may lead to the development of schizophrenia. The other factor is the gut-brain axis. The composition of the gut microbiome and alterations thereof may affect the brain and may lead to schizophrenia. The main interest of this review article is in overviewing the major recent findings on the effects of stress and the gut-brain axis, as well as their possible bidirectional effects, in the pathogenesis of schizophrenia.


Assuntos
Encéfalo/metabolismo , Suscetibilidade a Doenças , Retroalimentação Fisiológica , Trato Gastrointestinal/metabolismo , Esquizofrenia/etiologia , Esquizofrenia/metabolismo , Estresse Psicológico/complicações , Animais , Encéfalo/fisiopatologia , Microbioma Gastrointestinal , Humanos
13.
Cells ; 10(9)2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34572059

RESUMO

Tumour necrosis factor alpha (TNFα) is essential in neuroinflammatory modulation. Therefore, the goal of this study is to reveal the effects of chronic hyperglycaemia and insulin treatment on TNFα expression in different gut segments and intestinal wall layers. TNFα expression was mapped by fluorescent immunohistochemistry and quantitative immunogold electron microscopy in myenteric ganglia of duodenum, ileum and colon. Tissue TNFα levels were measured by enzyme-linked immunosorbent assays in muscle/myenteric plexus-containing (MUSCLE-MP) and mucosa/submucosa/submucous plexus-containing (MUC-SUBMUC-SP) homogenates. Increasing density of TNFα-labelling gold particles is observed in myenteric ganglia from proximal to distal segments and TNFα tissue levels are much more elevated in MUSCLE-MP homogenates than in MUC-SUBMUC-SP samples in healthy controls. In the diabetics, the number of TNFα gold labels is significantly increased in the duodenum, decreased in the colon and remained unchanged in the ileal ganglia, while insulin does not prevent these diabetes-related TNFα changes. TNFα tissue concentration is also increased in MUSCLE-MP homogenates of diabetic duodenum, while decreased in MUC-SUBMUC-SP samples of diabetic ileum and colon. These findings support that type 1 diabetes has region-specific and intestinal layer-dependent effects on TNFα expression, contributing to the regional damage of myenteric neurons and their intestinal milieu.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Trato Gastrointestinal/metabolismo , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Intestinos/fisiologia , Plexo Mientérico/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Experimental/patologia , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/patologia , Intestinos/efeitos dos fármacos , Masculino , Plexo Mientérico/efeitos dos fármacos , Plexo Mientérico/patologia , Ratos , Ratos Wistar
14.
Int J Mol Sci ; 22(16)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34445388

RESUMO

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide widely distributed in the central nervous system (CNS) and many peripheral organs, such as the digestive tract, endocrine, reproductive and respiratory systems, where it plays different regulatory functions and exerts a cytoprotective effect. The multifarious physiological effects of PACAP are mediated through binding to different G protein-coupled receptors, including PAC1 (PAC1-R), VPAC1 (VPAC1-R) and VPAC2 (VPAC2-R) receptors. In the gastrointestinal (GI) tract, PACAP plays an important regulatory function. PACAP stimulates the secretion of digestive juices and hormone release, regulates smooth muscle contraction, local blood flow, cell migration and proliferation. Additionally, there are many reports confirming the involvement of PACAP in pathological processes within the GI tract, including inflammatory states, neuronal injury, diabetes, intoxication and neoplastic processes. The purpose of this review is to summarize the distribution and pleiotropic action of PACAP in the control of GI tract function and its cytoprotective effect in the course of GI tract disorders.


Assuntos
Gastroenteropatias/diagnóstico , Trato Gastrointestinal/metabolismo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animais , Circulação Sanguínea , Proliferação de Células , Trato Gastrointestinal/irrigação sanguínea , Regulação da Expressão Gênica , Humanos
15.
Molecules ; 26(16)2021 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-34443679

RESUMO

Alcohol consumption is associated with gut dysbiosis, increased intestinal permeability, endotoxemia, and a cascade that leads to persistent systemic inflammation, alcoholic liver disease, and other ailments. Craving for alcohol and its consequences depends, among other things, on the endocannabinoid system. We have analyzed the relative role of central vs. peripheral cannabinoid CB1 receptors (CB1R) using a "two-bottle" as well as a "drinking in the dark" paradigm in mice. The globally acting CB1R antagonist rimonabant and the non-brain penetrant CB1R antagonist JD5037 inhibited voluntary alcohol intake upon systemic but not upon intracerebroventricular administration in doses that elicited anxiogenic-like behavior and blocked CB1R-induced hypothermia and catalepsy. The peripherally restricted hybrid CB1R antagonist/iNOS inhibitor S-MRI-1867 was also effective in reducing alcohol consumption after oral gavage, while its R enantiomer (CB1R inactive/iNOS inhibitor) was not. The two MRI-1867 enantiomers were equally effective in inhibiting an alcohol-induced increase in portal blood endotoxin concentration that was caused by increased gut permeability. We conclude that (i) activation of peripheral CB1R plays a dominant role in promoting alcohol intake and (ii) the iNOS inhibitory function of MRI-1867 helps in mitigating the alcohol-induced increase in endotoxemia.


Assuntos
Consumo de Bebidas Alcoólicas/patologia , Antagonistas de Receptores de Canabinoides/farmacologia , Endotoxemia/patologia , Etanol/efeitos adversos , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Receptor CB1 de Canabinoide/antagonistas & inibidores , Consumo de Bebidas Alcoólicas/sangue , Animais , Ansiedade/sangue , Ansiedade/complicações , Comportamento Animal/efeitos dos fármacos , Catalepsia/induzido quimicamente , Catalepsia/complicações , Cicloexanóis/administração & dosagem , Teste de Labirinto em Cruz Elevado , Endotoxemia/sangue , Endotoxemia/complicações , Endotoxinas/sangue , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/metabolismo , Hipotermia Induzida , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/metabolismo , Pirazóis/administração & dosagem , Receptor CB1 de Canabinoide/metabolismo , Rimonabanto/administração & dosagem , Rimonabanto/farmacologia , Estereoisomerismo , Sulfonamidas/administração & dosagem
16.
Nat Methods ; 18(8): 945-952, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34354290

RESUMO

Acoustic reporter genes (ARGs) that encode air-filled gas vesicles enable ultrasound-based imaging of gene expression in genetically modified bacteria and mammalian cells, facilitating the study of cellular function in deep tissues. Despite the promise of this technology for biological research and potential clinical applications, the sensitivity with which ARG-expressing cells can be visualized is currently limited. Here we present burst ultrasound reconstructed with signal templates (BURST)-an ARG imaging paradigm that improves the cellular detection limit by more than 1,000-fold compared to conventional methods. BURST takes advantage of the unique temporal signal pattern produced by gas vesicles as they collapse under acoustic pressure above a threshold defined by the ARG. By extracting the unique pattern of this signal from total scattering, BURST boosts the sensitivity of ultrasound to image ARG-expressing cells, as demonstrated in vitro and in vivo in the mouse gastrointestinal tract and liver. Furthermore, in dilute cell suspensions, BURST imaging enables the detection of gene expression in individual bacteria and mammalian cells. The resulting abilities of BURST expand the potential use of ultrasound for non-invasive imaging of cellular functions.


Assuntos
Escherichia coli/genética , Trato Gastrointestinal/metabolismo , Genes Reporter/genética , Fígado/metabolismo , Imagens de Fantasmas , Imagem Individual de Molécula/métodos , Ultrassonografia/métodos , Animais , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C
17.
Nutrients ; 13(8)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34444974

RESUMO

The administration of broad-spectrum antibiotics is often associated with antibiotic-associated diarrhea (AAD), and impacts gastrointestinal tract homeostasis, as evidenced by the following: (a) an overall reduction in both the numbers and diversity of the gut microbiota, and (b) decreased short-chain fatty acid (SCFA) production. Evidence in humans that probiotics may enhance the recovery of microbiota populations after antibiotic treatment is equivocal, and few studies have addressed if probiotics improve the recovery of microbial metabolic function. Our aim was to determine if Bifidobacterium animalis subsp. lactis BB-12 (BB-12)-containing yogurt could protect against antibiotic-induced fecal SCFA and microbiota composition disruptions. We conducted a randomized, allocation-concealed, controlled trial of amoxicillin/clavulanate administration (days 1-7), in conjunction with either BB-12-containing or control yogurt (days 1-14). We measured the fecal levels of SCFAs and bacterial composition at baseline and days 7, 14, 21, and 30. Forty-two participants were randomly assigned to the BB-12 group, and 20 participants to the control group. Antibiotic treatment suppressed the fecal acetate levels in both the control and probiotic groups. Following the cessation of antibiotics, the fecal acetate levels in the probiotic group increased over the remainder of the study and returned to the baseline levels on day 30 (-1.6% baseline), whereas, in the control group, the acetate levels remained suppressed. Further, antibiotic treatment reduced the Shannon diversity of the gut microbiota, for all the study participants at day 7. The magnitude of this change was larger and more sustained in the control group compared to the probiotic group, which is consistent with the hypothesis that BB-12 enhanced microbiota recovery. There were no significant baseline clinical differences between the two groups. Concurrent administration of amoxicillin/clavulanate and BB-12 yogurt, to healthy subjects, was associated with a significantly smaller decrease in the fecal SCFA levels and a more stable taxonomic profile of the microbiota over time than the control group.


Assuntos
Antibacterianos/efeitos adversos , Bifidobacterium animalis/metabolismo , Ácidos Graxos Voláteis/metabolismo , Fezes , Microbioma Gastrointestinal , Trato Gastrointestinal/microbiologia , Probióticos/uso terapêutico , Adolescente , Adulto , Idoso , Colo , Diarreia/etiologia , Diarreia/microbiologia , Diarreia/prevenção & controle , Fezes/química , Fezes/microbiologia , Trato Gastrointestinal/metabolismo , Humanos , Pessoa de Meia-Idade , Iogurte/microbiologia , Adulto Jovem
18.
Nutrients ; 13(7)2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34371955

RESUMO

Despite the well-established role of quinoa protein as the source of antihypertensive peptides through in vitro enzymolysis, there is little evidence supporting the in vivo antihypertensive effect of intact quinoa protein. In this study, in vivo study on spontaneously hypertensive rats (SHRs) was conducted by administering quinoa protein for five weeks. Gastrointestinal content identification indicated that many promising precursors of bioactive peptides were released from quinoa protein under gastrointestinal processing. Quinoa protein administration on SHRs resulted in a significant decrease in blood pressure, a significant increase in alpha diversity, and microbial structure alternation towards that in non-hypertension rats. Furthermore, blood pressure was highly negatively correlated with the elevated abundance of genera in quinoa protein-treated SHRs, such as Turicibacter and Allobaculum. Interestingly, the fecal microbiota in quinoa protein-treated SHRs shared more features in the composition of genera with non-hypertension rats than that of the captopril-treated group. These results indicate that quinoa protein may serve as a potential candidate to lower blood pressure and ameliorate hypertension-related gut dysbiosis.


Assuntos
Pressão Sanguínea , Captopril/administração & dosagem , Chenopodium quinoa , Proteínas na Dieta/administração & dosagem , Microbioma Gastrointestinal , Hipertensão/fisiopatologia , Proteínas de Plantas/administração & dosagem , Animais , Anti-Hipertensivos/administração & dosagem , Bactérias/classificação , Bactérias/isolamento & purificação , Proteínas na Dieta/metabolismo , Digestão , Fezes/microbiologia , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Hipertensão/tratamento farmacológico , Masculino , Peptídeos/análise , Proteínas de Plantas/metabolismo , Ratos , Ratos Endogâmicos SHR
19.
Nutrients ; 13(8)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34444752

RESUMO

Threonine (Thr), an essential amino acid for animals and the limiting amino acid in swine and poultry diets, which plays a vital role in the modulation of nutritional metabolism, macromolecular biosynthesis, and gut homeostasis. Current evidence supports that the supplementation of Thr leads to benefits in terms of energy metabolism. Threonine is not only an important component of gastrointestinal mucin, but also acts as a nutritional modulator that influences the intestinal immune system via complex signaling networks, particularly mitogen-activated protein kinase (MAPK) and the target of the rapamycin (TOR) signal pathway. Threonine is also recognized as an indispensable nutrient for cell growth and proliferation. Hence, optimization of Thr requirement may exert a favorable impact on the factors linked to health and diseases in animals. This review focuses on the latest reports of Thr in metabolic pathways and nutritional regulation, as well as the relationship between Thr and relevant physiological functions.


Assuntos
Metabolismo Energético , Estado Nutricional , Treonina/metabolismo , Aminoácidos/metabolismo , Animais , Dieta , Trato Gastrointestinal/metabolismo , Redes e Vias Metabólicas , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Mucinas/metabolismo , Sirolimo , Células-Tronco , Suínos
20.
Am J Physiol Endocrinol Metab ; 321(4): E443-E452, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34370594

RESUMO

Growth differentiating factor 15 (GDF15) is expressed in the intestine and is one of the most recently identified satiety peptides. The mechanisms controlling its secretion are unclear. The present study investigated whether plasma GDF15 concentrations are meal-related and if potential responses depend on macronutrient type or are affected by previous bariatric surgery. The study included 1) volunteers ingesting rapidly vs. slowly digested carbohydrates (sucrose vs. isomaltose; n = 10), 2) volunteers who had undergone Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) surgery and unoperated matched controls ingesting a liquid mixed meal (n = 9-10 in each group), and 3) individuals with previous RYGB compared with unoperated controls ingesting isocaloric glucose, fat, or protein (n = 6 in each group). Plasma was collected after an overnight fast and up to 6 h after ingestion (≥12 time points). In cohort 1, fasting GDF15 concentrations were ∼480 pg/mL. Concentrations after sucrose or isomaltose intake did not differ from baseline (P = 0.26 to P > 0.99) and total area under the curves (tAUCs were similar between groups (P = 0.77). In cohort 2, fasting GDF15 concentrations were as follows (pg/mL): RYGB = 540 ± 41.4, SG = 477 ± 36.4, and controls = 590 ± 41.8, with no between-group differences (P = 0.73). Concentrations did not increase at any postprandial time point (over all time factor: P = 0.10) and tAUCs were similar between groups (P = 0.73). In cohort 3, fasting plasma GDF15 was similar among the groups (P > 0.99) and neither glucose, fat, nor protein intake consistently increased the concentrations. In conclusion, we find that plasma GDF15 was not stimulated by meal intake and that fasting concentrations did not differ between RYGB-, SG-, and body mass index (BMI)-matched controls when investigated during the weight stable phase after RYGB and SG.NEW & NOTEWORTHY Our combined data show that GDF15 does not increase in response to a liquid meal. Moreover, we show for the first time that ingestion of sucrose, isomaltose, glucose, fat, or protein also does not increase plasma GDF15 concentrations, questioning the role of GDF15 in regulation of food source preference. Finally, we find that neither fasting nor postprandial plasma GDF15 concentrations are increased in individuals with previous bariatric surgery compared with unoperated body mass index (BMI)-matched controls.


Assuntos
Cirurgia Bariátrica/métodos , Biomarcadores/sangue , Trato Gastrointestinal/metabolismo , Fator 15 de Diferenciação de Crescimento/sangue , Refeições , Obesidade Mórbida/sangue , Adulto , Glicemia/análise , Índice de Massa Corporal , Estudos de Casos e Controles , Estudos Cross-Over , Feminino , Seguimentos , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/patologia , Obesidade Mórbida/cirurgia , Período Pós-Prandial , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Perda de Peso
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