RESUMO
Biological therapies only benefit one-third of patients with Crohn's disease (CD). For this reason, a deeper understanding of the mechanisms by which biologics elicit their effect on intestinal mucosa is needed. Increasing evidence points toward the involvement of long noncoding RNAs (lncRNAs) in the pathogenesis of CD, although their role remains poorly studied. We aimed to characterize lncRNA profiles in the ileum and colon from CD patients and evaluate the effect of anti-TNF-α treatment on their transcription. Terminal ileum and left colon samples from 30 patients (active CD = 10, quiescent CD = 10, and healthy controls (HCs) = 10) were collected for RNA-seq. The patients were classified according to endoscopic activity. Furthermore, biopsies were cultured with infliximab, and their transcriptome was determined by Illumina gene expression array. A total of 678 differentially expressed lncRNAs between the terminal ileum and left colon were identified in HCs, 438 in patients with quiescent CD, and 468 in patients with active CD. Additionally, we identified three new lncRNAs in the ileum associated with CD activity. No differences were observed when comparing the effect of infliximab according to intestinal location, presence of disease (CD vs. HC), and activity (active vs. quiescent). The expression profiles of lncRNAs are associated with the location of intestinal tissue, being very different in the ileum and colon. The presence of CD and disease activity are associated with the differential expression of lncRNAs. No modulatory effect of infliximab has been observed in the lncRNA transcriptome.
Assuntos
Doença de Crohn , RNA Longo não Codificante , Humanos , Doença de Crohn/tratamento farmacológico , Doença de Crohn/genética , Doença de Crohn/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Infliximab/farmacologia , Infliximab/uso terapêutico , Inibidores do Fator de Necrose Tumoral/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Colo/patologia , Íleo/metabolismo , Mucosa Intestinal/metabolismoRESUMO
The gastrointestinal tract is optimized to efficiently absorb nutrients and provide a competent barrier against a variety of lumen environmental compounds. Different regulatory mechanisms jointly collaborate to maintain intestinal homeostasis, but alterations in these mechanisms lead to a dysfunctional gastrointestinal barrier and are associated to several inflammatory conditions usually found in chronic pathologies such as inflammatory bowel disease (IBD). The gastrointestinal mucus, mostly composed of mucin glycoproteins, covers the epithelium and plays an essential role in digestive and barrier functions. However, its regulation is very dynamic and is still poorly understood. This review presents some aspects concerning the role of mucus in gut health and its alterations in IBD. In addition, the impact of gut microbiota and dietary compounds as environmental factors modulating the mucus layer is addressed. To date, studies have evidenced the impact of the three-way interplay between the microbiome, diet and the mucus layer on the gut barrier, host immune system and IBD. This review emphasizes the need to address current limitations on this topic, especially regarding the design of robust human trials and highlights the potential interest of improving our understanding of the regulation of the intestinal mucus barrier in IBD.
Assuntos
Microbioma Gastrointestinal/fisiologia , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/fisiopatologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/fisiologia , Muco/microbiologia , Muco/fisiologia , Animais , Dieta , Humanos , NutrientesRESUMO
The involvement of cancer stem-like cells (CSC) in the tumor pathogenesis has profound implications for cancer therapy and chemoprevention. Lunasin is a bioactive peptide from soybean and other vegetal sources with proven protective activities against cancer and other chronic diseases. The present study focused on the cytotoxic effect of peptide lunasin in colorectal cancer HCT-116 cells, both the bulk tumor and the CSC subpopulations. Lunasin inhibited the proliferation and the tumorsphere-forming capacity of HCT-116 cells. Flow cytometry results demonstrated that the inhibitory effects were related to apoptosis induction and cell cycle-arrest at G1 phase. Moreover, lunasin caused an increase in the sub-GO/G1 phase of bulk tumor cells, linked to the apoptotic events found. Immunoblotting analysis further showed that lunasin induced apoptosis through activation of caspase-3 and cleavage of PARP, and could modulate cell cycle progress through the cyclin-dependent kinase inhibitor p21. Together, these results provide new evidence on the chemopreventive activity of peptide lunasin on colorectal cancer by modulating both the parental and the tumorsphere-derived subsets of HCT-116 cells.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Peptídeos/farmacologia , Proteínas de Plantas/química , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Células HCT116 , Humanos , Peptídeos/química , Esferoides Celulares , Células Tumorais CultivadasRESUMO
BACKGROUND: There is an increasing interest toward the use of legumes in food industry, mainly due to the quality of their protein fraction. Many legumes are cultivated and consumed around the world, but few data is available regarding the chemical or technological characteristics, and especially on their suitability to be fermented. Nevertheless, sourdough fermentation with selected lactic acid bacteria has been recognized as the most efficient tool to improve some nutritional and functional properties. This study investigated the presence of lunasin-like polypeptides in nineteen traditional Italian legumes, exploiting the potential of the fermentation with selected lactic acid bacteria to increase the native concentration. An integrated approach based on chemical, immunological and ex vivo (human adenocarcinoma Caco-2 cell cultures) analyses was used to show the physiological potential of the lunasin-like polypeptides. RESULTS: Italian legume varieties, belonging to Phaseulus vulgaris, Cicer arietinum, Lathyrus sativus, Lens culinaris and Pisum sativum species, were milled and flours were chemically characterized and subjected to sourdough fermentation with selected Lactobacillus plantarum C48 and Lactobacillus brevis AM7, expressing different peptidase activities. Extracts from legume doughs (unfermented) and sourdoughs were subjected to western blot analysis, using an anti-lunasin primary antibody. Despite the absence of lunasin, different immunoreactive polypeptide bands were found. The number and the intensity of lunasin-like polypeptides increased during sourdough fermentation, as the consequence of the proteolysis of the native proteins carried out by the selected lactic acid bacteria. A marked inhibitory effect on the proliferation of human adenocarcinoma Caco-2 cells was observed using extracts from legume sourdoughs. In particular, sourdoughs from Fagiolo di Lamon, Cece dell'Alta Valle di Misa, and Pisello riccio di Sannicola flours were the most active, showing a decrease of Caco-2 cells viability up to 70 %. The over-expression of Caco-2 filaggrin and involucrin genes was also induced. Nine lunasin-like polypeptides, having similarity to lunasin, were identified. CONCLUSIONS: The features of the sourdough fermented legume flours suggested the use for the manufacture of novel functional foods and/or pharmaceuticals preparations.
Assuntos
Fabaceae/metabolismo , Peptídeos/metabolismo , Sequência de Aminoácidos , Reatores Biológicos , Células CACO-2 , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Proteínas Filagrinas , Farinha/análise , Microbiologia de Alimentos , Humanos , Proteínas de Filamentos Intermediários/genética , Proteínas de Filamentos Intermediários/metabolismo , Itália , Levilactobacillus brevis/crescimento & desenvolvimento , Levilactobacillus brevis/metabolismo , Lactobacillus plantarum/enzimologia , Lactobacillus plantarum/crescimento & desenvolvimento , Dados de Sequência Molecular , Peptídeos/genética , Peptídeos/farmacologia , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismo , RNA Mensageiro/metabolismo , Alinhamento de SequênciaRESUMO
BACKGROUND: The number of emerging pathogenic species described within the genus Arcobacter has increased rapidly during the last few years. In this work a genus-specific polymerase chain reaction (PCR) assay was developed for detection of the species of Arcobacter most commonly associated with foods. The assay uses primers designed to amplify an 85 bp DNA fragment on the 16S rRNA gene and was applied to the detection of Arcobacter spp. in retail chicken meat. RESULTS: Primer specificity was tested against a panel of Arcobacter spp., related Campylobacter and Helicobacter spp. and other food bacteria. Arcobacter primers consistently and selectively amplified the expected DNA fragment in all tested Arcobacter spp. Bacterial control primers confirmed the presence of amplifiable DNA in the samples. The applicability of the PCR assay to food was validated through screening of fresh retail chicken samples for the presence of Arcobacter spp., with a result of 45% (23 out of 51) positive samples. CONCLUSION: The genus-specific PCR assay developed has the potential to be used as a quick and sensitive alternative method for the survey of Arcobacter contamination in meats.
Assuntos
Arcobacter/genética , DNA Bacteriano/análise , Microbiologia de Alimentos , Carne/microbiologia , Reação em Cadeia da Polimerase/métodos , Animais , Técnicas de Tipagem Bacteriana , Galinhas , Primers do DNA , Dieta , RNA Ribossômico 16S/genética , Especificidade da EspécieRESUMO
The impact of food components on the human digestive system is an important area of research in the fields of nutrition and food science [...].
Assuntos
Tecnologia de Alimentos , Alimentos , Humanos , Estado Nutricional , Digestão , Sistema DigestórioRESUMO
Chlorella vulgaris and Tetraselmis chuii are two microalgae species already marketed because of their richness in high-value and health-beneficial compounds. Previous studies have demonstrated the biological properties of compounds isolated from both microalgae, although data are not yet available on the impact that pre-treatment and gastrointestinal digestion could exert on these properties. The aim of the present study was to analyze the impact of the biomass pre-treatment (freeze/thaw cycles plus ultrasounds) and simulated gastrointestinal digestion in the bioaccessibility and in vitro antioxidant activity (ABTS, ORAC, Q-FRAP, Q-DPPH) of the released digests. The cell wall from microalgae were susceptible to the pre-treatment and the action of saliva and gastric enzymes, releasing bioactive peptides and phenolic compounds that contributed to the potent antioxidant activity of digests through their radical scavenging and iron reduction capacities. Our findings suggest the potential of these microalgae against oxidative stress-associated diseases at both, intestinal and systemic level.
Assuntos
Antioxidantes , Chlorella vulgaris , Digestão , Trato Gastrointestinal , Microalgas , Modelos Biológicos , Antioxidantes/metabolismo , Antioxidantes/química , Antioxidantes/farmacologia , Chlorella vulgaris/química , Chlorella vulgaris/metabolismo , Microalgas/química , Microalgas/metabolismo , Humanos , Trato Gastrointestinal/metabolismo , Biomassa , Clorófitas/química , Clorófitas/metabolismoRESUMO
The estimated increase in world population will lead to a deterioration in global food security, aggravated in developing countries by hidden hunger resulting from protein deficiency. To reduce or avoid this crisis, a dietary shift towards the consumption of sustainable, nutrient-rich, and calorically efficient food products has been recommended by the FAO and WHO. Plant proteins derived from grains and seeds provide nutritionally balanced diets, improve health status, reduce poverty, enhance food security, and contain several functional compounds. In this review, the current evidence on the nutritional and functional properties of underutilized grains is summarized, focusing on their incorporation into functional foods and the role of their proteins as novel source of bioactive peptides with health benefits.
Assuntos
Dieta , Nutrientes , Sementes , Alimento Funcional , PeptídeosRESUMO
Inflammatory and oxidative processes are tightly regulated by innate and adaptive immune systems, which are involved in the pathology of a diversity of chronic diseases. Soybean peptides, such as lunasin, have emerged as one of the most hopeful food-derived peptides with a positive impact on health. The aim was to study the potential antioxidant and immunomodulatory activity of a lunasin-enriched soybean extract (LES). The protein profile of LES was characterized, and its behavior under simulated gastrointestinal digestion was evaluated. Besides its in vitro radical scavenging capacity, LES and lunasin's effects on cell viability, phagocytic capacity, oxidative stress, and inflammation-associated biomarkers were investigated in both RAW264.7 macrophages and lymphocytes EL4. Lunasin and other soluble peptides enriched after aqueous solvent extraction partially resisted the action of digestive enzymes, being potentially responsible for the beneficial effects of LES. This extract scavenged radicals, reduced reactive oxygen species (ROS) and exerted immunostimulatory effects, increasing nitric oxide (NO) production, phagocytic activity, and cytokine release in macrophages. Lunasin and LES also exerted dose-dependent immunomodulatory effects on EL4 cell proliferation and cytokine production. The modulatory effects of soybean peptides on both immune cell models suggest their potential protective role against oxidative stress, inflammation, and immune response-associated disorders.
Assuntos
Peptídeos , Proteínas de Soja , Proteínas de Soja/farmacologia , Peptídeos/farmacologia , Glycine max/química , Inflamação , Citocinas/metabolismo , Extratos Vegetais/metabolismoRESUMO
Inflammatory bowel disease (IBD) is an idiopathic and chronic disorder that includes ulcerative colitis (UC) and Crohn's disease (CD). Both diseases show an uncontrolled intestinal immune response that generates tissue inflammation. Dendritic cells (DCs) are antigen-presenting cells that play a key role in tolerance maintenance in the gastrointestinal mucosa. Although it has been reported that DC recruitment by the intestinal mucosa is more prominent in IBD patients, the specific mechanisms governing this migration are currently unknown. In this study, the expression of several homing markers and the migratory profile of circulating DC subsets towards intestinal chemo-attractants were evaluated and the effect of biological drugs with different mechanisms of action, such as anti-TNFα or anti-integrin α4ß7 (vedolizumab), on this mechanism in healthy controls (HCs) and IBD patients was also assessed. Our results revealed that type 2 conventional DCs (cDC2) express differential homing marker profiles in UC and CD patients compared to HCs. Indeed, integrin ß7 was differentially modulated by vedolizumab in CD and UC. Additionally, although CCL2 displayed a chemo-attractant effect over cDC2, while biological therapies did not modulate the expression of the homing markers, we paradoxically found that anti-TNF-treated cDC2 increased their migratory capacity towards CCL2 in HCs and IBD. Our results therefore suggest a key role for cDC2 migration towards the intestinal mucosa in IBD, something that could be explored in order to develop novel diagnostic biomarkers or to unravel new immunomodulatory targets in IBD.
RESUMO
BACKGROUND: Intestinal dendritic cells (DC) and macrophages drive disease progression in patients with inflammatory bowel disease (IBD). We aimed to characterize the activation and homing profile of human circulating DC and monocyte subsets in healthy control patients (CP) and IBD patients. METHODS: Eighteen CP and 64 patients with IBD were categorized by diagnoses of Crohn disease (CD) and ulcerative colitis (UC), either endoscopically active (inflamed) or quiescent. Circulating type 1 conventional DC, type 2 conventional DC, plasmacytoid DC, classical monocytes, nonclassical monocytes, and intermediate monocytes were identified by flow cytometry in each individual and characterized for the expression of 18 markers. Association between DC/monocytes and IBD risk was tested by logistic regression. Discriminant canonical analyses were performed to classify the patients in their own endoscopy category considering all markers on each subset. RESULTS: CCRL1, CCR3, and CCR5 expression on circulating type 1 DC; CCRL1 expression on nonclassical monocytes; and CCR9 and ß7 expression on classical monocytes allowed us to discriminate among the different study groups. Indeed, the same markers (excluding ß7) were also associated with IBD when all DC and monocyte subsets were considered at the same time. CONCLUSIONS: Monitoring the phenotype of human circulating DC and monocyte subsets may provide novel tools as biomarkers for disease diagnosis (CD/UC) or mucosal status (inflamed/noninflamed) in the absence of an invasive colonoscopy.
Assuntos
Colite Ulcerativa , Doença de Crohn , Células Dendríticas/imunologia , Monócitos/imunologia , Biomarcadores , Colite Ulcerativa/imunologia , Doença de Crohn/imunologia , Humanos , FenótipoRESUMO
INTRODUCTION: Lunasin is a soybean bioactive peptide with a variety of beneficial properties against chronic disorders. However, its effect in human primary intestinal cells remains unknown. Hence, this study aims to characterize its ex vivo biological activity in the human intestinal mucosa. METHODS AND RESULTS: Human intestinal biopsies, obtained from healthy controls, are ex vivo conditioned with lunasin both in the presence/absence of lipopolysaccharide (LPS). Peptide maintains its stability during biopsy culture by HPLC-MS/MS analysis. Lunasin is bioactive in the human mucosa, as it induces IL-1ß, TNF-α, IL-17A, CCL2, and PGE2/COX-2 gene expression together with an increased expression of tolerogenic IL-10 and TGFß, while it also downregulates the expression of iNOS and subunit p65 from NF-κB. Indeed, lunasin also abrogates the LPS-induced pro-inflammatory response, downregulating IL-17A, IFNγ, and IL-8 expression, and inducing IL-10 and TGFß expression. These results are also mirrored in the cell-free culture supernatants at the protein level by Multiplex. Moreover, lunasin further induces a regulatory phenotype and function on human intestinal conventional dendritic cell and macrophage subsets as assessed by flow cytometry. CONCLUSIONS: We hereby have characterized lunasin as an immunomodulatory peptide with potential capacity to prevent immune and inflammatory-mediated disorders in the human gastrointestinal tract.
Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Proteínas de Soja/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Células Apresentadoras de Antígenos/efeitos dos fármacos , Citocinas/metabolismo , Humanos , Lipopolissacarídeos/farmacologia , Proteínas de Soja/imunologiaRESUMO
The gastrointestinal tract represents a specialized interface between the organism and the external environment. Because of its direct contact with lumen substances, the modulation of digestive functions by dietary substances is supported by a growing body of evidence. Food-derived bioactive peptides have demonstrated a plethora of activities in the organism with increasing interest toward their impact over the digestive system and related physiological effects. This review updates the biological effects of food proteins, specifically milk and soybean proteins, associated to gastrointestinal health and highlights the study of digestion products and released peptides, the identification of the active form/s, and the evaluation of the mechanisms of action underlying their relationship with the digestive cells and receptors. The approach toward the modifications that food proteins and peptides undergo during gastrointestinal digestion and their bioavailability is a crucial step for current investigations on the field. The recent literature on the regulation of digestive functions by peptides has been mostly considered in terms of their influence on gastrointestinal motility and signaling, oxidative damage and inflammation, and malignant cellular proliferation. A final section regarding the actual challenges and future perspectives in this scientific topic is critically discussed.
Assuntos
Anticarcinógenos/farmacologia , Proteínas Alimentares/farmacocinética , Digestão/fisiologia , Peptídeos/farmacologia , Animais , Alimento Funcional , Motilidade Gastrointestinal/efeitos dos fármacos , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Proteínas do Leite/farmacocinética , Peptídeos/farmacocinética , Receptores Opioides/metabolismo , Proteínas de Soja/farmacocinéticaRESUMO
Adipose tissue secretes molecules that can promote activity in Crohn's disease. We aimed to evaluate the role of serum adipokines as possible biomarkers in Crohn's disease. Serum samples were obtained from 40 patients with endoscopically active or quiescent Crohn's disease and 36 healthy controls. Serum leptin, ghrelin, resistin and adiponectin levels were analysed by Multiplex in a Luminex 200 system technology. Receiver Operating Characteristic curves were performed to evaluate the adipokines discriminatory capacity. A logistic regression adjusted by possible confounders (i.e. gender, age, BMI) was performed for those adipokines that showed an area under the curve > 0.7. No differences were found in age, gender or BMI among groups. Distribution for serum resistin was different among the three groups of study, and only this adipokine showed an area under the curve of 0.75 comparing actives patients and healthy control groups. Resistin median concentration was selected as a cut-off for a logistic regression analysis; odds ratio along its 95% confidence interval adjusted by gender, age, and BMI yielded a value of 5.46 (1.34-22.14) comparing actives patients and healthy controls. High concentration of serum resistin is probably associated to activity, being this association independent of gender, age or BMI.
Assuntos
Adipocinas/sangue , Biomarcadores/sangue , Doença de Crohn/diagnóstico , Adiponectina/sangue , Adulto , Estudos de Casos e Controles , Doença de Crohn/sangue , Feminino , Seguimentos , Grelina/sangue , Humanos , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Resistina/sangueRESUMO
Non-communicable diseases have become the medical challenge of the 21st century because of their high incidence and mortality rates. Accumulating evidence has suggested that the modulation of diet and other lifestyle habits is the best strategy for the prevention of these diseases. An increasing number of dietary compounds have been found to exert health promoting benefits beyond their nutritional effects. Among them, lunasin is considered one of the most studied bioactive peptides. Since its discovery in soybean twenty years ago, many researchers around the world have focused their studies on demonstrating the chemopreventive and chemotherapeutic activity of lunasin. Moreover, in the last years, promising protective effects of this peptide against hypercholesterolemia, obesity, metabolic syndrome and associated cardiovascular disorders, and inflammatory and immune-regulated diseases have been described. This review summarizes recent remarkable advances on the use of peptide lunasin as a potential functional ingredient to provide health benefits. Moreover, novel aspects related to the influence of lunasin's digestion and bioavailability, the mechanisms of action proposed to explain the underlying biological properties, and the incorporation of this peptide into nutritional supplements are critically discussed.
Assuntos
Glycine max/química , Peptídeos/química , Proteínas de Plantas/química , Proteínas de Plantas/uso terapêutico , Proteínas de Soja/química , Proteínas de Soja/uso terapêutico , Disponibilidade Biológica , Doenças Cardiovasculares/prevenção & controle , Quimioprevenção , Doença Crônica , Suplementos Nutricionais , Hipercolesterolemia/prevenção & controle , Síndrome Metabólica/prevenção & controle , Obesidade/prevenção & controleRESUMO
Oxidative stress, inflammation, and hypertension are recognized risk factors for non-communicable diseases. Because of the preventable character of these factors, the searching of dietary compounds with counteracting effects against them would provide a new framework for the development of novel multifunctional foods or nutraceuticals. Lunasin is a naturally occurring soybean peptide with chemopreventive and anti-inflammatory properties. Upon oral intake, lunasin is susceptible to the action of digestive enzymes during its transit through gastrointestinal tract. In spite of its cleavage into smaller peptides, these fragments have been suggested to contribute on the health beneficial effects attributed to lunasin. To confirm this hypothesis, the multifunctionality of lunasin derived-fragments was investigated. In vitro, peptides corresponding to the N-terminal and central regions of lunasin were demonstrated to inhibit angiotensin converting enzyme and to scavenge peroxyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) radicals. Moreover, lunasin and fragments released during its gastrointestinal digestion exerted potent protective effects on cell viability and oxidative status in macrophages RAW264.7 challenged with chemicals tert-butylhydroperoxide and hydrogen peroxide. These peptides were also able to reduce the nitric oxide production in pro-inflammatory lipopolysaccharide-induced macrophages. These results confirm the promising role of lunasin and its derived-fragments as protective agents against oxidative damage and inflammation-associated diseases.
Assuntos
Antioxidantes , Modelos Biológicos , Proteínas de Soja , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Digestão , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Peptídeos/química , Peptídeos/metabolismo , Peptídeos/farmacologia , Células RAW 264.7 , Proteínas de Soja/química , Proteínas de Soja/metabolismo , Proteínas de Soja/farmacologiaRESUMO
Bioactive peptides secreted by probiotic Bifidobacterium longum (peptide B7) and opportunistic pathogen Bacteroides fragilis (peptide B12) modulate the intestinal cytokine milieu in health. Here, we characterized their capacity to modulate both the mucosal cytokine production and the phenotype of circulating antigen presenting cells (APCs) in active inflammatory bowel disease (IBD). The IBD mucosa produced higher levels of pro-inflammatory cytokines referred to healthy controls (HCs). Peptides B7 and B12, however, did not ameliorate the mucosal cytokine milieu in IBD. Human circulating APCs (B-cells, monocytes, plasmacytoid dendritic cells (pDCs), and conventional dendritic cells (cDCs)) were characterized by flow cytometry in presence/absence of the peptides. Circulating B-cells, monocytes, and cDCs from IBD patients were more activated than those from HCs. Peptide B7, but not B12, decreased CCR2 expression on all APC subsets from HC, but not IBD patients. Moreover, both peptides tend to further increase their pro-inflammatory profile in IBD. In summary, IBD patients display mucosal and circulating APC pro-inflammatory properties. Peptide B7 immunomodulatory capacity elicited over circulating APCs from HC, but not IBD patients, suggests the presence of disrupted modulatory mechanisms for this peptide in IBD. Future studies should address the effect of bacteria-derived immunomodulatory peptides in non-inflamed (quiescent) IBD patients.
Assuntos
Células Apresentadoras de Antígenos , Proteínas de Bactérias/farmacologia , Citocinas , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Células Apresentadoras de Antígenos/efeitos dos fármacos , Células Apresentadoras de Antígenos/imunologia , Células Apresentadoras de Antígenos/metabolismo , Produtos Biológicos/farmacologia , Células Cultivadas , Citocinas/efeitos dos fármacos , Citocinas/metabolismo , Humanos , Imunomodulação/efeitos dos fármacos , Imunomodulação/imunologia , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Peptídeos/farmacologiaRESUMO
Cranberries (Vaccinium macrocarpon) are full of polyphenols, which display various health benefits. Most studies have focused on extractable polyphenols (EPs) rather than non-extractable polyphenols (NEPs) but NEPs may possess important biological functions. The objective of this work was to characterize EP and NEP fractions from whole cranberries and determine their potential as anti-inflammation and anti-colon-cancer agents. Our results showed that of the identified polyphenols, anthocyanins were the major ones in the cranberry EP fraction, while phenolic acids were most abundant in the NEP fraction. The oxygen radical absorbance capacity (ORAC) of the NEPs was significantly higher than that of the EPs. Both the EPs and NEPs showed anti-inflammatory effects in inhibiting LPS-induced production of nitric oxide in macrophages. At the concentrations tested, the NEPs showed significantly higher inhibition of the production of nitric oxide in macrophages than the EPs, which was accompanied by decreased expression of inducible nitric oxide synthase (iNOS) and increased expression of HO-1. EP and NEP samples showed anti-cancer capacities in HCT116 cells. And the NEPs showed stronger inhibitory effects on the viability and colony formation capacity of human colon cancer HCT116 cells than the EPs. In a flow cytometry analysis, the NEPs caused cell cycle arrest at the G0/G1 phase and induced significant cellular apoptosis in colon cancer cells. Overall, our results suggested that both the EP and NEP fractions from cranberries were bioactive, and importantly, the NEP fraction showed promising anti-inflammation and anti-colon-cancer potential.
Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Vaccinium macrocarpon/química , Anti-Inflamatórios/química , Antineoplásicos/química , Neoplasias do Colo/genética , Neoplasias do Colo/imunologia , Neoplasias do Colo/fisiopatologia , Frutas/química , Frutas/metabolismo , Células HCT116 , Heme Oxigenase-1/genética , Heme Oxigenase-1/imunologia , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Óxido Nítrico/imunologia , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/imunologia , Extratos Vegetais/química , Polifenóis/química , Vaccinium macrocarpon/metabolismoRESUMO
Lunasin is a naturally-occurring peptide demonstrating chemopreventive, antioxidant and anti-inflammatory properties. To exhibit these activities, orally ingested lunasin needs to survive proteolytic attack of digestive enzymes to reach target tissues in active form/s. Preliminary studies suggested the protective role of protease inhibitors, such as the Bowman-Birk inhibitor and Kunitz-trypsin inhibitor, against lunasin's digestion by both pepsin and pancreatin. This work describes in depth the behaviour of lunasin under conditions simulating the transit through the gastrointestinal tract in the absence or presence of soybean Bowman-Birk isoinhibitor 1 (IBB1) in both active and inactive states. By liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS), the remaining lunasin at the end of gastric and gastro-duodenal phases was quantified. Protection against the action of pepsin was independent of the amount of IBB1 present in the analyzed samples, whereas an IBB1 dose-dependent protective effect against trypsin and chymotrypsin was observed. Peptides released from lunasin and inactive IBB1 were identified by MS/MS. The remaining lunasin and IBB1 as well as their derived peptides could be responsible for the anti-proliferative activity against colon cancer cells observed for the digests obtained at the end of simulated gastrointestinal digestion.
Assuntos
Proliferação de Células , Neoplasias do Colo/fisiopatologia , Trato Gastrointestinal/metabolismo , Glycine max/metabolismo , Peptídeos/química , Proteínas de Soja/metabolismo , Inibidor da Tripsina de Soja de Bowman-Birk/metabolismo , Sequência de Aminoácidos , Linhagem Celular , Neoplasias do Colo/dietoterapia , Neoplasias do Colo/metabolismo , Digestão , Trato Gastrointestinal/química , Humanos , Modelos Biológicos , Dados de Sequência Molecular , Peptídeos/metabolismo , Sementes/química , Sementes/metabolismo , Alinhamento de Sequência , Proteínas de Soja/química , Glycine max/química , Inibidor da Tripsina de Soja de Bowman-Birk/químicaRESUMO
Milk is the most complete food for mammals, as it supplies all the energy and nutrients needed for the proper growth and development of the neonate. Milk is a source of many bioactive components, which not only help meeting the nutritional requirements of the consumers, but also play a relevant role in preventing various disorders. Milk-derived proteins and peptides have the potential to act as coadjuvants in conventional therapies, addressing cardiovascular diseases, metabolic disorders, intestinal health, and chemopreventive properties. In addition to being a source of proteins and peptides, milk contains complex oligosaccharides that possess important functions related to the newborn's development and health. Some of the health benefits attributed to milk oligosaccharides include prebiotic probifidogenic effects, antiadherence of pathogenic bacteria, and immunomodulation. This review focuses on recent findings demonstrating the biological activities of milk peptides, proteins, and oligosaccharides towards the prevention of diseases of the 21st century. Processing challenges hindering large-scale production and commercialization of those bioactive compounds have been also addressed.