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1.
PLoS One ; 15(8): e0234750, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785220

RESUMO

The incidence of nonalcoholic steatohepatitis (NASH) is increasing worldwide, including in Asian countries. We reported that the hepatic expression of bile salt export pump (BSEP) was downregulated in patients with NASH, suggesting that BSEP is involved in the pathogenesis of NASH. To identify the underlying mechanism, we analyzed Bsep heterozygous knock-out (Bsep+/- mice) and wild-type (WT) C57BL/6J mice fed a high-fat diet (HFD) (32.0% animal fat) or normal diet. We examined histological changes, levels of hepatic lipids and hepatic bile acids, and expression of genes related to bile acid and cholesterol metabolism. HFD-fed Bsep+/- mice exhibited milder hepatic steatosis and less weight gain, compared to HFD-fed WT mice. The concentrations of total bile acid, triglycerides, and cholesterols were reduced in the liver of HFD-fed Bsep+/- mice. Regarding hepatic bile acid metabolism, the expression levels of Farnesoid X receptor (Fxr) and Multidrug resistance-associated protein 2 were significantly upregulated in HFD-fed Bsep+/- mice, compared to HFD-fed WT mice. Furthermore, several alterations were observed in upstream cholesterol metabolism in the liver. The expression levels of bile acid metabolism-related genes were also altered in the intestine of HFD-fed Bsep+/- mice. In conclusion, HFD-fed Bsep+/- mice exhibited significant alterations of the expression levels of genes related to bile acid and lipid metabolism in both the liver and ileum, resulting in alleviated steatosis and less weight gain. These results suggest the importance of BSEP for maintenance of bile acid and cholesterol metabolism. Further investigations of the involvement of BSEP in the pathogenesis of NASH will provide greater insight and facilitate the development of novel therapeutic modalities.


Assuntos
Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/deficiência , Dieta Hiperlipídica/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/genética , Animais , Ácidos e Sais Biliares/metabolismo , Colesterol/metabolismo , Modelos Animais de Doenças , Heterozigoto , Íleo/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/patologia
2.
PLoS One ; 15(8): e0236657, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760089

RESUMO

Crohn's disease is a pathological condition of the gastro-intestinal tract, causing severe transmural inflammation in the ileum and/or colon. Cigarette smoking is one of the best known environmental risk factors for the development of Crohn's disease. Nevertheless, very little is known about the effect of prolonged cigarette smoke exposure on inflammatory modulators in the gut. We examined the effect of cigarette smoke on cytokine profiles in the healthy and inflamed gut of human subjects and in the trinitrobenzene sulphonic acid mouse model, which mimics distal Crohn-like colitis. In addition, the effect of cigarette smoke on epithelial expression of transient receptor potential channels and their concurrent increase with cigarette smoke-augmented cytokine production was investigated. Active smoking was associated with increased IL-8 transcription in ileum of controls (p < 0,001; n = 18-20/group). In the ileum, TRPV1 mRNA levels were decreased in never smoking Crohn's disease patients compared to healthy subjects (p <0,001; n = 20/group). In the colon, TRPV1 mRNA levels were decreased (p = 0,046) in smoking healthy controls (n = 20/group). Likewise, healthy mice chronically exposed to cigarette smoke (n = 10/group) showed elevated ileal Cxcl2 (p = 0,0075) and colonic Kc mRNA levels (p = 0,0186), whereas TRPV1 mRNA and protein levels were elevated in the ileum (p = 0,0315). Although cigarette smoke exposure prior to trinitrobenzene sulphonic acid administration did not alter disease activity, increased pro-inflammatory cytokine production was observed in the distal colon (Kc: p = 0,0273; Cxcl2: p = 0,104; Il1-ß: p = 0,0796), in parallel with the increase of Trpv1 mRNA (p < 0,001). We infer that CS affects pro-inflammatory cytokine expression in healthy and inflamed gut, and that the simultaneous modulation of TRPV1 may point to a potential involvement of TRPV1 in cigarette smoke-induced production of inflammatory mediators.


Assuntos
Colo/metabolismo , Doença de Crohn/metabolismo , Íleo/metabolismo , Canais de Cátion TRPV/metabolismo , Fumar Tabaco/efeitos adversos , Adulto , Idoso , Animais , Células CACO-2 , Colo/patologia , Doença de Crohn/induzido quimicamente , Doença de Crohn/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Células HT29 , Humanos , Íleo/patologia , Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Pesquisa Médica Translacional , Ácido Trinitrobenzenossulfônico
3.
J Oleo Sci ; 69(9): 1077-1085, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32788520

RESUMO

There is growing research interest in the hypocholesterolemic effect of various food components such as polyphenols. In this study, we examined the effects of oligonol-a low-molecular weight polyphenol extracted from lychee fruit-on cholesterol metabolism in rats under short-term administration. Administration of oligonol for 3 days significantly increased cecum weight and decreased cecal n-butyric acid concentrations in rats. Oligonol also significantly lowered the levels of hepatic cholesterol and increased the levels of total neutral steroids excreted in the feces. It also increased fecal ß-muricholic acid significantly, whereas the levels of total acidic steroids remained unchanged. Gene expression of hepatic CYP7A1 (cytochrome P450 family 7 subfamily A member 1) significantly increased following the administration of oligonol. This increase could be ascribed to changes in the expression of farnesoid X receptor, small heterodimer partner, and fibroblast growth factor 15 in ileum. Our data suggest that oligonol induces hypocholesterolemic effects through the inhibition of biliary cholesterol absorption from the intestine and the upregulation of cholesterol catabolism in rats even following short-term administration. Therefore, oligonol may be an important food component for reducing cholesterol level.


Assuntos
Catequina/análogos & derivados , Colesterol/metabolismo , Litchi/química , Fenóis/isolamento & purificação , Fenóis/farmacologia , Animais , Butiratos/metabolismo , Catequina/administração & dosagem , Catequina/isolamento & purificação , Catequina/farmacologia , Colesterol 7-alfa-Hidroxilase/genética , Colesterol 7-alfa-Hidroxilase/metabolismo , Expressão Gênica/efeitos dos fármacos , Íleo/metabolismo , Fígado/metabolismo , Masculino , Peso Molecular , Fenóis/administração & dosagem , Polifenóis , Ratos Wistar , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Fatores de Tempo
4.
Nat Commun ; 11(1): 3612, 2020 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-32681035

RESUMO

Bile acid synthesis plays a key role in regulating whole body cholesterol homeostasis. Transcriptional factor EB (TFEB) is a nutrient and stress-sensing transcriptional factor that promotes lysosomal biogenesis. Here we report a role of TFEB in regulating hepatic bile acid synthesis. We show that TFEB induces cholesterol 7α-hydroxylase (CYP7A1) in human hepatocytes and mouse livers and prevents hepatic cholesterol accumulation and hypercholesterolemia in Western diet-fed mice. Furthermore, we find that cholesterol-induced lysosomal stress feed-forward activates TFEB via promoting TFEB nuclear translocation, while bile acid-induced fibroblast growth factor 19 (FGF19), acting via mTOR/ERK signaling and TFEB phosphorylation, feedback inhibits TFEB nuclear translocation in hepatocytes. Consistently, blocking intestinal bile acid uptake by an apical sodium-bile acid transporter (ASBT) inhibitor decreases ileal FGF15, enhances hepatic TFEB nuclear localization and improves cholesterol homeostasis in Western diet-fed mice. This study has identified a TFEB-mediated gut-liver signaling axis that regulates hepatic cholesterol and bile acid homeostasis.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Ácidos e Sais Biliares/metabolismo , Colesterol/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Animais , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/antagonistas & inibidores , Linhagem Celular , Colesterol 7-alfa-Hidroxilase/metabolismo , Dieta Ocidental/efeitos adversos , Modelos Animais de Doenças , Células Hep G2 , Humanos , Hipercolesterolemia/etiologia , Hipercolesterolemia/metabolismo , Hipercolesterolemia/prevenção & controle , Íleo/efeitos dos fármacos , Íleo/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Transportadores de Ânions Orgânicos Dependentes de Sódio/antagonistas & inibidores , Simportadores/antagonistas & inibidores
5.
PLoS One ; 15(7): e0236950, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32730335

RESUMO

The use of natural products as feed additives in the poultry industry is increasing; however, most studies focus on performance and growth with little regard for determining mechanism. Our laboratory designed a chicken (Gallus gallus)-specific immunometabolic kinome peptide array. Using this tool to examine the active enzymes responsible for phosphorylation events (kinases) provides important information on host and cellular functions. The objective of this project was to determine if feeding a microencapsulated product comprised of a blend of organic acids and botanicals (AviPlus®P) impacts the intestinal kinome of broiler chickens (Gallus gallus). Day-of-hatch chicks were provided 0 or 500g/MT of the additive and jejunal and ileal segments collected for kinome analysis to determine the mode-of-action of the additive. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed by uploading the statistically significant peptides to the Search Tool for the Retrieval of Interacting Genes database. As a whole, GO and KEGG analysis showed similar activities in the ileum and jejunum. However, there were a small number of KEGG pathways that were only activated in either the ileum or jejunum, but not both. Analysis of the adipocytokine and PI3K-AKT signaling pathways showed differences between ileal and jejunal activity that were controlled, in part, by AKT3. Additionally, cytokine/chemokine evaluation showed the ileum had higher IL1ß, IL6, IL10, TNFα, IFNγ, CXCL8, and CCL4 mRNA expression levels (P<0.05). As a whole, the data showed the addition of microencapsulated organic acids and botanicals to a broiler diet activated many of the same signaling pathways in the ileum and jejunum; however, distinctions were observed. Taken together, the findings of this study begin to define the mode-of-action that microencapsulated organic acids and botanicals have on two important intestinal segments responsible for nutrient digestion and absorption in chickens.


Assuntos
Ácidos/farmacologia , Dieta/veterinária , Íleo/metabolismo , Jejuno/metabolismo , Compostos Fitoquímicos/farmacologia , Proteínas Quinases/metabolismo , Ração Animal/análise , Animais , Galinhas , Perfilação da Expressão Gênica , Íleo/efeitos dos fármacos , Jejuno/efeitos dos fármacos , Plantas/química , Análise Serial de Proteínas , Proteínas Quinases/genética
6.
PLoS One ; 15(6): e0232831, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32497096

RESUMO

The burden of enteric pathogens in poultry is growing after the ban of antibiotic use in animal production. Organic acids gained attention as a possible alternative to antibiotics due to their antimicrobial activities, improved nutrient metabolism and performance. The current study was conducted to evaluate the effectiveness of organic acid blend on broilers cecal microbiota, histomorphometric measurements, and short-chain fatty acid production in Salmonella enterica serovar Typhimurium challenge model. Birds were divided into four treatments, including a negative control, positive control challenged with S. Typhimurium, group supplemented with an organic acid blend, and birds supplemented with organic acid blend and Salmonella challenged. Results illustrate significant differences in feed conversion ratios and production efficiency factor between treatment groups, however, the influence of organic acid supplement was marginal. Organic acid blend significantly increased cecal acetic and butyric acids concentrations when compared to unsupplemented groups and resulted in minor alterations of intestinal bacterial communities.


Assuntos
Acetatos/metabolismo , Ração Animal , Butiratos/metabolismo , Galinhas/microbiologia , Suplementos Nutricionais , Ácidos Graxos/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Doenças das Aves Domésticas/terapia , Salmonelose Animal/terapia , Salmonella typhimurium/efeitos dos fármacos , Animais , Ceco/microbiologia , Galinhas/metabolismo , Ácidos Graxos/administração & dosagem , Ácidos Graxos Voláteis/administração & dosagem , Ácidos Graxos Voláteis/farmacologia , Íleo/metabolismo , Íleo/ultraestrutura , Mananas/administração & dosagem , Microvilosidades/ultraestrutura , Doenças das Aves Domésticas/microbiologia , Doenças das Aves Domésticas/prevenção & controle , Distribuição Aleatória , Salmonelose Animal/microbiologia , Salmonelose Animal/prevenção & controle , Salmonella typhimurium/isolamento & purificação , Salmonella typhimurium/metabolismo
7.
J Anim Sci ; 98(6)2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32437583

RESUMO

Indigestible fiber-protein-phytate complexes reduce the feeding value of soy products. We investigated the effects of multienzyme supplement (MES, Victus) on standardized ileal digestibility (SID) of amino acids (AA) and apparent total tract digestibility (ATTD) of energy and minerals in roasted full-fat soybean (FFSB) seeds and expelled-extruded soybean meal (SBM) fed to growing pigs. The crude protein (CP) was 33.4% and 42.8% dry matter (DM) in FFSB seeds and SBM, respectively and corresponding values for crude fat were 17.4% and 11.8% DM. Semi-purified diets with 50% of either FFSB seeds or SBM as the sole source of AA were prepared without or with MES supplying phytase, protease, xylanase, and ß-glucanase at 2,200, 8,300, 400, and 100 U/kg of feed, respectively. Diets had TiO2 as an indigestible marker and the ratio of cornstarch to sucrose and corn oil was identical to calculate DE by the difference method. Eight ileal-cannulated barrows (22.1 ± 0.61 kg) were fed diets in a replicated 4 × 4 Latin square design to give eight replicates per diet. The period lasted for 9 d: 5 d for acclimation, 2 d for fecal, and 2 d for ileal digesta samples. There was no (P > 0.05) interaction between soy type and MES or MES effect on SID of AA; SBM had higher (P < 0.05) SID of CP, His, Leu, and Lys. There was no (P > 0.05) interaction between soy type and MES on energy digestibility. The FFSB seeds had higher ATTD of gross energy (GE, 80.2% vs. 76.6%; P < 0.01) than SBM. Pigs fed MES had higher (P < 0.05) ATTD of DM (91.3% vs. 87.7 %), GE (87.5% vs. 82.4%), CP (86.4% vs. 82.9%), crude fat (70.6% vs. 54.9%), Ca (63.2% vs. 60.2%), and P (67.5% vs. 63.2%). In conclusions, differences on AA and energy digestibility in soy products could be linked to processing and compositional differences. Although MES had no effect on SID of AA, the effects on the utilization of minerals and energy demonstrated the value of fiber-degrading enzymes, protease, and phytase in improving the nutritive value of soy products independent of processing.


Assuntos
Ração Animal/análise , Digestão/fisiologia , Manipulação de Alimentos , Complexos Multienzimáticos/administração & dosagem , Soja/química , Suínos/fisiologia , 6-Fitase/farmacologia , Aminoácidos/metabolismo , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Dieta/veterinária , Suplementos Nutricionais , Íleo/metabolismo , Masculino , Minerais/metabolismo , Valor Nutritivo , Ácido Fítico/metabolismo , Sementes/metabolismo
9.
Science ; 369(6499): 50-54, 2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-32358202

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause coronavirus disease 2019 (COVID-19), an influenza-like disease that is primarily thought to infect the lungs with transmission through the respiratory route. However, clinical evidence suggests that the intestine may present another viral target organ. Indeed, the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) is highly expressed on differentiated enterocytes. In human small intestinal organoids (hSIOs), enterocytes were readily infected by SARS-CoV and SARS-CoV-2, as demonstrated by confocal and electron microscopy. Enterocytes produced infectious viral particles, whereas messenger RNA expression analysis of hSIOs revealed induction of a generic viral response program. Therefore, the intestinal epithelium supports SARS-CoV-2 replication, and hSIOs serve as an experimental model for coronavirus infection and biology.


Assuntos
Betacoronavirus/fisiologia , Enterócitos/virologia , Íleo/virologia , Replicação Viral , Betacoronavirus/ultraestrutura , Técnicas de Cultura de Células , Diferenciação Celular , Linhagem da Célula , Proliferação de Células , Meios de Cultura , Enterócitos/metabolismo , Enterócitos/ultraestrutura , Expressão Gênica , Humanos , Íleo/metabolismo , Íleo/ultraestrutura , Pulmão/virologia , Masculino , Organoides , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Virais/genética , Receptores Virais/metabolismo , Mucosa Respiratória/virologia , Vírus da SARS/fisiologia
10.
Inflamm Bowel Dis ; 26(6): 797-808, 2020 05 12.
Artigo em Inglês | MEDLINE | ID: covidwho-116826

RESUMO

BACKGROUND: Patients with inflammatory bowel disease (IBD) have intestinal inflammation and are treated with immune-modulating medications. In the face of the coronavirus disease-19 pandemic, we do not know whether patients with IBD will be more susceptible to infection or disease. We hypothesized that the viral entry molecules angiotensin I converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are expressed in the intestine. We further hypothesized that their expression could be affected by inflammation or medication usage. METHODS: We examined the expression of Ace2 and Tmprss2 by quantitative polymerase chain reacion in animal models of IBD. Publicly available data from organoids and mucosal biopsies from patients with IBD were examined for expression of ACE2 and TMPRSS2. We conducted RNA sequencing for CD11b-enriched cells and peripheral and lamina propria T-cells from well-annotated patient samples. RESULTS: ACE2 and TMPRSS2 were abundantly expressed in the ileum and colon and had high expression in intestinal epithelial cells. In animal models, inflammation led to downregulation of epithelial Ace2. Expression of ACE2 and TMPRSS2 was not increased in samples from patients with compared with those of control patients. In CD11b-enriched cells but not T-cells, the level of expression of ACE2 and TMPRSS2 in the mucosa was comparable to other functional mucosal genes and was not affected by inflammation. Anti-tumor necrosis factor drugs, vedolizumab, ustekinumab, and steroids were linked to significantly lower expression of ACE2 in CD11b-enriched cells. CONCLUSIONS: The viral entry molecules ACE2 and TMPRSS2 are expressed in the ileum and colon. Patients with IBD do not have higher expression during inflammation; medical therapy is associated with lower levels of ACE2. These data provide reassurance for patients with IBD.


Assuntos
Regulação da Expressão Gênica , Imunossupressores/farmacologia , Síndrome do Intestino Irritável/fisiopatologia , Peptidil Dipeptidase A/genética , Serina Endopeptidases/genética , Adolescente , Adulto , Idoso , Animais , Betacoronavirus/metabolismo , Biópsia , Colo/efeitos dos fármacos , Colo/metabolismo , Biologia Computacional , Infecções por Coronavirus/fisiopatologia , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Íleo/efeitos dos fármacos , Íleo/metabolismo , Imunossupressores/uso terapêutico , Inflamação/fisiopatologia , Mucosa Intestinal/metabolismo , Síndrome do Intestino Irritável/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/fisiopatologia , Reação em Cadeia da Polimerase em Tempo Real , Transcriptoma , Adulto Jovem
11.
Artigo em Inglês | MEDLINE | ID: mdl-32348179

RESUMO

The serotonin transporter (SERT) functions to regulate the availability of serotonin (5-HT) in the brain and intestine. An intestine-specific mRNA variant arising from a unique transcription start site and alternative promoter in the SERT gene has been identified (iSERT; spanning exon 1C). A decrease in SERT is implicated in several gut disorders, including inflammatory bowel diseases (IBD). However, little is known about mechanisms regulating the iSERT variant, and a clearer understanding is warranted for targeting SERT for the treatment of gut disorders. The current studies examined the expression of iSERT across different human intestinal regions and investigated its regulation by HNF4α (hepatic nuclear factor-4α), a transcription factor important for diverse cellular functions. iSERT mRNA abundance was highest in the human ileum and Caco-2 cell line. iSERT mRNA expression was downregulated by loss of HNF4α (but not HNF1α, HNF1ß, or FOXA1) in Caco-2 cells. Overexpression of HNF4α increased iSERT mRNA concomitant with an increase in SERT protein. Progressive promoter deletion and site-directed mutagenesis revealed that the HNF4α response element spans nucleotides -1,163 to -1150 relative to the translation start site. SERT mRNA levels in the intestine were drastically reduced in the intestine-specific HNF4α-knockout mice relative to HNF4αFL/FL mice. Both HNF4α and SERT mRNA levels were also downregulated in mouse model of ileitis (SAMP) compared with AKR control mice. These results establish the transcriptional regulation of iSERT at the gut-specific internal promoter (hSERTp2) and have identified HNF4α as a critical modulator of basal SERT expression in the intestine.


Assuntos
Células Epiteliais/metabolismo , Fator 4 Nuclear de Hepatócito/metabolismo , Ileíte/metabolismo , Íleo/metabolismo , Mucosa Intestinal/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Animais , Células CACO-2 , Modelos Animais de Doenças , Células Epiteliais/patologia , Fator 4 Nuclear de Hepatócito/deficiência , Fator 4 Nuclear de Hepatócito/genética , Humanos , Ileíte/genética , Ileíte/patologia , Íleo/patologia , Mucosa Intestinal/patologia , Masculino , Camundongos Knockout , Regiões Promotoras Genéticas , Elementos de Resposta , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Transcrição Genética
12.
J Dairy Sci ; 103(6): 5003-5018, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32229117

RESUMO

5-Fluorouracil (5-FU) is widely used as a chemotherapeutic drug for the treatment of cancer but it has toxic side effects. It can induce severe intestinal damage and even lead to death. The purpose of this study was to investigate whether milk fermented with Lactobacillus rhamnosus FLRH93 could alleviate intestinal damage induced by 5-FU. The results of injury intervention in a mouse model showed that milk fermented with Lb. rhamnosus FLRH93 significantly ameliorated intestinal injury caused by 5-FU. The results of hematoxylin and eosin staining showed that mice fed Lb. rhamnosus FLRH93 preserved the villus/crypt ratio and reduced the loss of goblet cells in ileum sections of 5-FU-treated animal. Further, administration of fermented milk upregulated expression of Bcl-2 in the intestinal tract and downregulated the expression of NLRP3, thus reducing the production of inflammatory factors interleukin 1-ß and tumor necrosis factor-α. The survival rate of mice treated with fermented milk was twice that of mice not fed fermented milk after continuous oral administration of 5-FU. In conclusion, Lb. rhamnosus FLRH93 has positive effects on body injury and could be used to prevent intestinal damage caused by cancer chemotherapy.


Assuntos
Fluoruracila/efeitos adversos , Enteropatias/terapia , Lactobacillus rhamnosus/fisiologia , Probióticos/uso terapêutico , Animais , Modelos Animais de Doenças , Feminino , Íleo/metabolismo , Interleucina-1beta/metabolismo , Enteropatias/induzido quimicamente , Camundongos , Camundongos Endogâmicos BALB C , Leite/metabolismo , Substâncias Protetoras/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima
13.
J Anim Sci ; 98(5)2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32285108

RESUMO

Five experiments were conducted to determine the standardized total tract digestibility (STTD) of P, digestible energy (DE), metabolizable energy (ME), and standardized ileal digestibility (SID) of amino acids (AA) in three sorghum varieties compared with corn and to determine the effects of sorghum varieties on nursery pig growth. In exp. 1, 48 barrows (initially 18.6 kg) were housed individually in metabolism crates. Treatments were arranged in a 2 × 4 factorial evaluating two levels of microbial phytase (0 or 500 units/kg) and four grain sources (corn, high-lysine, red, or white sorghum). Added phytase improved (P < 0.05) STTD of P in all ingredients, but was not different among the grains. In exp. 2, the DE and ME in the three sorghum varieties were not different from corn. In exp. 3, 10 growing barrows (initially 25.9 kg) with a T-cannula in the terminal ileum were used. Standardized ileal digestible Lys, Met, Thr, and Val were greater (P < 0.05) in corn than in the sorghum-based diets with no differences among the sorghum varieties. In exp. 4, 160 pigs (initially 6.3 kg) were randomly allotted to one of four dietary treatments with five pigs per pen and eight replicate pens per treatment in a 20-d experiment. Dietary treatments included corn or the three sorghum varieties, where the varieties of sorghum replaced corn on an SID Lys basis. No differences among treatments were observed in any growth performance parameters. In exp. 5, treatments consisted of a corn-based diet, a diet based on conventional sorghum (a mixture of red and white sorghum), and four diets with high-lysine sorghum containing increasing amounts of feed-grade AA, replacing soybean meal. Overall, pigs fed the high-lysine sorghum diet with the greatest amount of added feed-grade AA had the poorest gain:feed ratio (G:F; P < 0.05) compared with pigs fed all the other experimental diets. Within those fed the high-lysine sorghum and feed-grade AA, average daily gain, final body weight (linear, P < 0.10), and G:F (linear, P < 0.01) decreased as feed-grade AA increased. In summary, no differences in STTD of P or in DE and ME were observed among the grain sources. The SID AA values for the three sorghum varieties were not different; however, they were all lower than for corn. These results indicate that these varieties of sorghum can successfully replace corn in nursery pig diets if diets are formulated to account for differences in AA digestibility.


Assuntos
Ração Animal/análise , Dieta/veterinária , Sorghum/genética , Suínos/crescimento & desenvolvimento , 6-Fitase/metabolismo , Aminoácidos/metabolismo , Fenômenos Fisiológicos da Nutrição Animal , Animais , Digestão , Metabolismo Energético , Íleo/metabolismo , Lisina/metabolismo , Masculino , Sorghum/metabolismo , Soja/química , Zea mays/metabolismo
14.
Poult Sci ; 99(4): 1847-1861, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32241465

RESUMO

The dynamic development of the animal intestine with a concurrent succession of microbiota and changes in microbial community and metabolite spectrum can exert far-reaching effects on host physiology. However, the precise mechanism of mutual response between microbiota and the gut is yet to be fully elucidated. Broilers with varying developmental degrees of intestinal wall thickness were selected, and they were divided into the thick group (H type) and the thin group (B type), using multiomics data integration analysis to reveal the fundamental regulatory mechanisms of gut-microbiota interplay. Our data showed, in broilers with similar body weight, the intestinal morphological parameters were improved in H type and the diversity of microbial communities is distinguishable from each other. The beneficial bacteria such as Bifidobacterium breve was increased whereas avian endogenous retrovirus EAV-HP was decreased in the H type compared with the B type. Furthermore, microbial metabolic potentials were more active, especially the biosynthesis of folate was improved in the H type. Similarly, the consolidation of absorption, immunity, metabolism, and development was noticed in the thick group. Correlation analysis indicated that the expression levels of material transport and immunomodulatory-related genes were positively correlated with the relative abundance of several probiotics such as B. breve, Lactobacillus saerimneri, and Butyricicoccus pullicaecorum. Our findings suggest that the chickens with well-developed ileal thickness own exclusive microbial composition and metabolic potential, which is closely related to small intestinal morphogenesis and homeostasis.


Assuntos
Galinhas/genética , Galinhas/microbiologia , Expressão Gênica , Interações entre Hospedeiro e Microrganismos , Microbiota , Animais , Proteínas Aviárias/genética , Proteínas Aviárias/metabolismo , Fenômenos Fisiológicos Bacterianos , Íleo/metabolismo , Intestinos/fisiologia , Masculino
15.
Environ Toxicol ; 35(9): 982-990, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32333507

RESUMO

In this work, we aimed to evaluate the adverse effects and the mechanism of intestinal barrier caused by titanium dioxide nanoparticles (TiO2 NPs). Here, the effects of two different dosages (300 and 1200 mg/kg) of TiO2 NPs on female mice (n = 5) were investigated. After 28-day oral exposure, the results of Ti content were significantly increased in the ileum in comparison with the control. The histopathological structure index of the ileum was significantly changed after TiO2 NPs exposure; villi height and crypt depth were decreased and increased, respectively. Meanwhile, TiO2 NPs treatment also significantly altered the transcription levels of genes. First, the GATA-3 and STAT-4 were upregulation and downregulation, respectively. Second, gene expressions of the Zonula Occludens-1, claudin (CLDN)-12, occludin, and myosin light chain kinase were significantly upregulated, while the CLDN-3 was decreased. Finally, the caspase-3, caspase-9, and caspase-12 were upregulated. The results of TUNEL staining indicated apoptosis in the ileum. In general, TiO2 NPs treatment significantly changed the intestine physical barrier in a dose-dependent manner. The toxicity of TiO2 NPs could be through the imbalance in the Th1/Th2.


Assuntos
Apoptose/efeitos dos fármacos , Íleo/efeitos dos fármacos , Nanopartículas/toxicidade , Equilíbrio Th1-Th2/efeitos dos fármacos , Titânio/toxicidade , Administração Oral , Animais , Relação Dose-Resposta a Droga , Feminino , Íleo/imunologia , Íleo/metabolismo , Íleo/patologia , Camundongos , Nanopartículas/ultraestrutura , Tamanho da Partícula , Propriedades de Superfície , Titânio/química , Titânio/farmacocinética
16.
Inflamm Bowel Dis ; 26(6): 797-808, 2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32333601

RESUMO

BACKGROUND: Patients with inflammatory bowel disease (IBD) have intestinal inflammation and are treated with immune-modulating medications. In the face of the coronavirus disease-19 pandemic, we do not know whether patients with IBD will be more susceptible to infection or disease. We hypothesized that the viral entry molecules angiotensin I converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are expressed in the intestine. We further hypothesized that their expression could be affected by inflammation or medication usage. METHODS: We examined the expression of Ace2 and Tmprss2 by quantitative polymerase chain reacion in animal models of IBD. Publicly available data from organoids and mucosal biopsies from patients with IBD were examined for expression of ACE2 and TMPRSS2. We conducted RNA sequencing for CD11b-enriched cells and peripheral and lamina propria T-cells from well-annotated patient samples. RESULTS: ACE2 and TMPRSS2 were abundantly expressed in the ileum and colon and had high expression in intestinal epithelial cells. In animal models, inflammation led to downregulation of epithelial Ace2. Expression of ACE2 and TMPRSS2 was not increased in samples from patients with compared with those of control patients. In CD11b-enriched cells but not T-cells, the level of expression of ACE2 and TMPRSS2 in the mucosa was comparable to other functional mucosal genes and was not affected by inflammation. Anti-tumor necrosis factor drugs, vedolizumab, ustekinumab, and steroids were linked to significantly lower expression of ACE2 in CD11b-enriched cells. CONCLUSIONS: The viral entry molecules ACE2 and TMPRSS2 are expressed in the ileum and colon. Patients with IBD do not have higher expression during inflammation; medical therapy is associated with lower levels of ACE2. These data provide reassurance for patients with IBD.


Assuntos
Regulação da Expressão Gênica , Imunossupressores/farmacologia , Síndrome do Intestino Irritável/fisiopatologia , Peptidil Dipeptidase A/genética , Serina Endopeptidases/genética , Adolescente , Adulto , Idoso , Animais , Betacoronavirus/metabolismo , Biópsia , Colo/efeitos dos fármacos , Colo/metabolismo , Biologia Computacional , Infecções por Coronavirus/fisiopatologia , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Íleo/efeitos dos fármacos , Íleo/metabolismo , Imunossupressores/uso terapêutico , Inflamação/fisiopatologia , Mucosa Intestinal/metabolismo , Síndrome do Intestino Irritável/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/fisiopatologia , Reação em Cadeia da Polimerase em Tempo Real , Transcriptoma , Adulto Jovem
17.
J Anim Sci ; 98(4)2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32201878

RESUMO

Three experiments were conducted to investigate the effects of dietary crude protein (CP) level and N-carbamylglutamate (NCG) supplementation on apparent total tract digestibility (ATTD) and ileal digestibility of nutrients and digestive enzyme activity of jejunum in growing pigs. In experiment 1, 10 Duroc × Landrace × Yorkshire barrows (initial BW: 48.7 kg) were allotted to a three-period switchback design with five experimental diets and two replicate pigs per diet in each period. Diets were categorized as high CP (HP, 18% CP), moderate low CP (MLP, 15% CP), very low CP (VLP, 12% CP), and MLP and VLP with 0.1% NCG supplementation. Feces and urine were collected from day 6 to day 11 after a 5-d adaptation period. The DE, ME, and ATTD of GE, OM, CP, NDF, ADF, and P decreased (P < 0.01) with a reduction of dietary CP, but no effect of dietary treatments on pig daily N retention was detected. The NCG supplementation increased (P < 0.01) DE and ATTD of ADF of the VLP diet. In experiment 2, 10 jejunal-cannulated Duroc × Landrace × Yorkshire barrows (initial BW: 44.5 kg) were fed five diets for three periods as experiment 1. Jejunal fluid was collected on days 6 and 8 after a 5-d adaptation period. The digestive enzymes activity was not affected by dietary CP level, except for α-amylase, for which there was a decrease (P < 0.01) in pigs fed VLP diets compared to HP and MLP diets. In experiment 3, 12 ileal-cannulated Duroc × Landrace × Yorkshire barrows (initial BW: 46.7 kg) were allotted to a three-period switchback design with six diets and two replicate pigs per diet in each period. The six experimental diets consisted of five experimental diets as experiment 1 and one N-free diet. Ileal digesta was collected from day 6 to day 8 after a 5-d adaptation period. Results indicated that apparent ileal digestibility (AID) of CP and P and ileal digestibility of Arg, His, Ile, Leu, Phe, and all dispensable AA, except Pro, decreased (P < 0.01) in pigs fed VLP diet compared to HP and MLP diets, but AID of GE, OM, EE, NDF, and ADF were not affected. The supplementation of NCG in the VLP diet increased (P < 0.01) the AID of CP and ileal digestibility of Arg, His, Leu, Phe, Val, Ser, and Tyr. In conclusion, reducing dietary CP level decreased nutrient digestibility, but improved the efficiency of dietary N utilization and reduced N emission. Moderate reduction of dietary CP level had a minimal effect on nutrient digestibility and digestive enzyme activity. Additionally, NCG supplementation plays a beneficial effect on nutrient digestion only if the dietary CP level is extremely lowered.


Assuntos
Ração Animal/análise , Dieta/veterinária , Proteínas na Dieta/administração & dosagem , Glutamatos/administração & dosagem , Suínos/fisiologia , Aminoácidos/metabolismo , Fenômenos Fisiológicos da Nutrição Animal , Animais , Proteínas na Dieta/farmacologia , Suplementos Nutricionais , Digestão/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Trato Gastrointestinal/metabolismo , Glutamatos/farmacologia , Íleo/metabolismo , Jejuno/metabolismo , Masculino
18.
J Dairy Sci ; 103(5): 4236-4251, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32171512

RESUMO

This study evaluated how feeding colostrum- or a colostrum-milk mixture for 3 d postnatal affects plasma glucagon-like peptide-2 (GLP-2), serum insulin-like growth factor-1 (IGF-1), and small intestinal histomorphology in calves. Holstein bulls (n = 24) were fed colostrum at 2 h postnatal and randomly assigned to receive either colostrum (COL), whole milk (WM), or a 1:1 COL:WM mixture (MIX) every 12 h from 12 to 72 h. A jugular venous catheter was placed at 1 h postnatal to sample blood frequently for the duration of the experiment. Samples were collected at 1, 2, 3, 6, 9, 11, and 12 h. Following the 12-h meal, blood was collected at half-hour intervals until 16 h and then at 1-h intervals from 16 to 24 h. A 27-h sample was taken, then blood was sampled every 6 h from 30 to 60 h. Again, blood was taken at half-intervals from 60 to 64 h, then at 65 and 66 h, following which, a 2-h sampling interval was used until 72 h. Plasma GLP-2 (all time points) and serum IGF-1 (at time points: 1, 6, 12, 18, 24, 36, 48, and 72 h) were both analyzed. Duodenal, jejunal, and ileal tissues were collected at 75 h of age to assess histomorphology and cellular proliferation. Feeding COL, rather than WM, increased plasma GLP-2 by 60% for 2 h and tended to increase GLP-2 by 49.4% for 4 h after the 60-h meal. Insulin-like growth factor-1 area under the curve (from 12 to 72 h) tended to be 27% greater for COL than WM calves but was otherwise unaffected by treatment. Ileal crypts tended to proliferate more with MIX than WM, whereas ileal crypt proliferation did not differ for COL compared with MIX or WM and was not different between treatments in the proximal jejunum. Villi height was increased 1.8 and 1.5× (COL and MIX vs. WM) in the proximal and distal jejunum, respectively, whereas MIX duodenal and ileal villi height tended to be 1.5 and 1.4× that of WM. Crypt depth did not differ in any region. Surface area of the gastrointestinal tract was reduced for WM by 60 and 58% (proximal jejunum) and 38 and 52% (ileum) relative to COL and MIX and was 54% less than MIX in the distal jejunum. Overall, extended COL feeding minimally increased plasma GLP-2 and serum IGF-1 compared with WM feeding. As COL and MIX similarly promoted small intestinal maturation, feeding calves transition milk to promote intestinal development could be a strategy for producers.


Assuntos
Ração Animal , Bovinos , Colostro , Peptídeo 2 Semelhante ao Glucagon/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Intestino Delgado/crescimento & desenvolvimento , Leite , Animais , Animais Recém-Nascidos , Bovinos/sangue , Dieta/veterinária , Íleo/crescimento & desenvolvimento , Íleo/metabolismo , Mucosa Intestinal/metabolismo , Jejuno/crescimento & desenvolvimento , Jejuno/metabolismo , Masculino
19.
Poult Sci ; 99(3): 1528-1539, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32111320

RESUMO

Two experiments were performed, using broilers or turkeys, each utilizing a 3 × 2 factorial arrangement, to compare their response to phytase and xylanase supplementation with growth performance, nutrient digestibility, and ileal phytate degradation as response criteria. For both experiments, 960 Ross 308 or 960 BUT 10 (0-day-old) birds were allocated to 6 treatments: (1) control diet, containing phytase at 500 FTU/kg; (2) the control diet with xylanase (16,000 BXU/kg); (3) the control diet supplemented on top with phytase (1,500 FTU/kg); (4) diet supplemented with 1,500 FTU/kg phytase and xylanase (16,000 BXU/kg); (5) the control diet supplemented with phytase (3,000 FTU/kg); and (6) diet supplemented with 3,000 FTU/kg phytase and xylanase (16,000 BXU/kg). Each treatment had 8 replicates of 20 birds each. Water and diets based on wheat, soybean meal, oilseed rape meal, and barley were available ad libitum. Body weight gain and feed intake were measured from 0 to 28 D, and feed conversion ratio (FCR) corrected for mortality was calculated. Ileal digestibility for dry matter and minerals on day 7 and 28 were analyzed in addition to levels of inositol phosphate esters (InsP6-3) and myo-inositol. Statistical comparisons were performed using ANOVA. Xylanase supplementation improved 28D FCR in broilers and turkeys. Increasing doses of phytase reduced FI and improved FCR only in broilers. In broilers, the age × phytase interaction for phosphorous digestibility showed that increasing phytase dose was more visible on day 7, than on day 28. Mineral digestibility was lower in 28-day-old turkey compared with 7-day-old turkey. InsP6 disappearance increased with increasing phytase levels in both species, with lower levels analyzed in turkeys. InsP6 disappearance was greater in younger turkeys (day 7 compared with day 28). In conclusion, although broilers and turkeys shared several similarities in their growth and nutrient utilization responses, the outcomes of the 2 trials also differed in many aspects. Whether this is because of difference in diets (InsP or Ca level) or differences between species needs further investigation.


Assuntos
6-Fitase/metabolismo , Galinhas/fisiologia , Digestão/efeitos dos fármacos , Endo-1,4-beta-Xilanases/metabolismo , Minerais/metabolismo , Ácido Fítico/metabolismo , Perus/fisiologia , 6-Fitase/administração & dosagem , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Galinhas/crescimento & desenvolvimento , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Endo-1,4-beta-Xilanases/administração & dosagem , Íleo/metabolismo , Masculino , Perus/crescimento & desenvolvimento
20.
Radiat Res ; 193(5): 435-450, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32134361

RESUMO

Mitigation of total-body irradiation (TBI) in C57BL/6 mice by two drugs, which target apoptosis and necroptosis respectively, increases survival compared to one drug alone. Here we investigated whether the biomarker (signature)directed addition of a third anti-ferroptosis drug further mitigated TBI effects. C57BL/6NTac female mice (30-33 g) received 9.25 Gy TBI, and 24 h or later received JP4-039 (20 mg/kg), necrostatin-1 (1.65 mg/kg) and/or lipoxygenase-15 inhibitor (baicalein) (50 mg/kg) in single-, dual- or three-drug regimens. Some animals were sacrificed at days 0, 1, 2, 3, 4 or 7 postirradiation, while the majority in each group were maintained beyond 30 days. For those mice sacrificed at the early time points, femur bone marrow, intestine (ileum), lung and blood plasma were collected and analyzed for radiation-induced and mitigator-modified levels of 33 pro-inflammatory and stress response proteins. Each single mitigator administered [JP4-039 (24 h), necrostatin-1 (48 h) or baicalein (24 h)] improved survival at day 30 after TBI to 25% (P = 0.0432, 0.2816 or 0.1120, respectively) compared to 5% survival of 9.25 Gy TBI controls. Mice were administered the drug individually based on weight (mg/kg). Drug vehicles comprised 30% cyclodextrin for JP4-039 and baicalein, and 10% Cremphor-EL/10% ethanol/80% water for necrostatin-1; thus, dual-vehicle controls were also tested. The dual-drug combinations further enhanced survival: necrostatin-1 (delayed to 72 h) with baicalein 40% (P = 0.0359); JP4-039 with necrostatin-1 50% (P = 0.0062); and JP4-039 with baicalein 60% (P = 0.0064). The three-drug regimen, timed to signature directed evidence of onset after TBI of each death pathway in marrow and intestine, further increased the 30-day survival to 75% (P = 0.0002), and there was optimal normalization to preirradiation levels of inflammatory cytokine and stress response protein levels in plasma, intestine and marrow. In contrast, lung protein levels were minimally altered by 9.25 Gy TBI or mitigators over 7 days. Significantly, elevated intestinal proteins at day 7 after TBI were reduced by necrostatin-1-containing regimens; however, normalization of plasma protein levels at day 7 required the addition of JP4-039 and baicalein. These findings indicate that mitigator targeting to three distinct cell death pathways increases survival after TBI.


Assuntos
Apoptose/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Necroptose/efeitos dos fármacos , Protetores contra Radiação/farmacologia , Irradiação Corporal Total/efeitos adversos , Animais , Apoptose/efeitos da radiação , Medula Óssea/efeitos dos fármacos , Medula Óssea/metabolismo , Medula Óssea/efeitos da radiação , Citocinas/metabolismo , Interações Medicamentosas , Feminino , Ferroptose/efeitos da radiação , Íleo/efeitos dos fármacos , Íleo/metabolismo , Íleo/efeitos da radiação , Camundongos , Camundongos Endogâmicos C57BL , Necroptose/efeitos da radiação , Lesões Experimentais por Radiação/patologia , Lesões Experimentais por Radiação/prevenção & controle , Bibliotecas de Moléculas Pequenas/farmacologia , Fatores de Tempo
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