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1.
DNA Cell Biol ; 39(11): 1926-1937, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33001759

RESUMO

GPR84 is an inflammation-induced receptor highly expressed on immune cells, yet its endogenous ligand is still unknown. This makes any interpretation of its physiological activity in vivo difficult. However, experiments with potent synthetic agonists have highlighted what the receptor can do, namely, enhance proinflammatory signaling and macrophage effector functions such as phagocytosis. Developing drugs to block these effects has attracted interest from the scientific community with the aim of decreasing disease activity in inflammatory disorders or enhancing inflammation resolution. In this review, we critically reassess the widely held belief that the major role of GPR84 is that of being a medium-chain fatty acid (MCFA) receptor. While MCFAs have been shown to activate GPR84, it remains to be demonstrated that they are present in relevant tissues at appropriate concentrations. In contrast to four other "full-time" free fatty acid receptor subtypes, GPR84 is not expressed by enteroendocrine cells and has limited expression in the gastrointestinal tract. Across multiple tissues and cell types, the highest expression levels of GPR84 are observed hours after exposure to an inflammatory stimulus. These factors obscure the relationship between ligand and receptor in the human body and do not support the exclusive physiological pairing of MCFAs with GPR84. To maximize the chances of developing efficacious drugs for inflammatory diseases, we must advance our understanding of GPR84 and what it does in vivo.


Assuntos
Ácidos Graxos/genética , Inflamação/genética , Receptores Acoplados a Proteínas-G/genética , Ácidos Graxos/metabolismo , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/patologia , Humanos , Inflamação/metabolismo , Inflamação/patologia , Ligantes , Macrófagos/metabolismo , Fagocitose/genética , Transdução de Sinais/genética
2.
Aquat Toxicol ; 228: 105629, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33002683

RESUMO

Hepatic in vitro biotransformation assays, in combination with in vitro-in vivo extrapolation (IVIVE) and bioaccumulation modeling, can be used to support regulatory bioaccumulation assessments. In most applications, however, these methods ignore the possibility of extrahepatic metabolism. Here we evaluated intestinal biotransformation in rainbow trout using S9 fractions prepared from the upper intestinal (GIT) epithelium. Measured levels of activity determined using standard substrates for phase I and phase II biotransformation enzymes were within 2-fold of activities measured in hepatic S9 fractions. In vitro intrinsic clearance rates for 2-ethylhexyl-4-methoxycinnamate (EHMC; an organic sunscreen agent) and two polycyclic aromatic hydrocarbons (pyrene [PYR] and benzo(a)pyrene [BAP]) were significantly higher in liver S9 fractions than in GIT S9 fractions. For octocrylene (OCT; a second sunscreen agent), however, in vitro intrinsic clearance rates were higher in GIT S9 fractions compared to liver S9 fractions. An existing 'liver only' IVIVE model was expanded to consider biotransformation in both the liver and GIT. Relevant IVIVE scaling factors were developed by morphological, histological, and biochemical evaluation of trout intestines. For chemicals biotransformed at higher rates by hepatic S9 fractions (i.e., BAP, PYR, EHMC), the 'liver & GIT' model yielded whole-body biotransformation rate constants (kMET) that were within 1.2 to 1.4-fold of those estimated using the 'liver only' model. In contrast to these findings, the mean kMET for OCT obtained using the 'liver & GIT' model was 3.3 times higher than the mean kMET derived using the 'liver only' model and was in good agreement with empirical kMET estimates determined previously for trout (<20 % difference). The results of this study suggest that current 'liver only' IVIVE approaches may underestimate in vivo biotransformation rates for chemicals that undergo substantial biotransformation in the GIT.


Assuntos
Trato Gastrointestinal/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Fígado/metabolismo , Oncorhynchus mykiss/metabolismo , Animais , Biotransformação/efeitos dos fármacos , Cinética , Taxa de Depuração Metabólica , Tamanho do Órgão , Poluentes Químicos da Água/toxicidade
3.
Anim Sci J ; 91(1): e13455, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33025683

RESUMO

This study aimed to evaluate nutrient intake and digestibility, enteric methane emission and nitrogen utilization efficiency in Nellore cattle ranked by residual feed intake (RFI). Twenty-four Nellore bulls at 466 ± 24 days of age and with 352 ± 14.6 kg of body weight, classified as low and high RFI, were evaluated. Animals were kept in individual pens for three periods of 28 days and variables were measured. Data were analyzed as repeated measures over time, considering as fixed effects RFI class, period and RFI class x period interaction, and linear (co)variate of age. No significant differences in dry matter or nutrient intake were detected between RFI classes, but total digestible nutrients intake tended to be lower in low RFI animals, and apparent nutrient digestibility was higher in high RFI animals. Partial efficiency of growth tended to be lower in high RFI animals. RFI class did not interfere with enteric methane production or microbial protein synthesis, but fecal nitrogen output was higher in low RFI animals. The greater efficiency of low RFI animals is consequence of lower maintenance requirements, since energy from higher nutrients digestibility in high RFI animals was spent on metabolic processes other than body tissue deposition.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Comportamento Animal , Bovinos/metabolismo , Bovinos/fisiologia , Dieta/veterinária , Digestão , Ingestão de Alimentos , Comportamento Alimentar , Trato Gastrointestinal/metabolismo , Gases de Efeito Estufa/metabolismo , Metano/metabolismo , Nitrogênio/metabolismo , Animais , Masculino
4.
Emerg Microbes Infect ; 9(1): 2169-2179, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32969768

RESUMO

Studies on patients with the coronavirus disease-2019 (COVID-19) have implicated that the gastrointestinal (GI) tract is a major site of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We established a human GI tract cell line model highly permissive to SARS-CoV-2. These cells, C2BBe1 intestinal cells with a brush border having high levels of transmembrane serine protease 2 (TMPRSS2), showed robust viral propagation, and could be persistently infected with SARS-CoV-2, supporting the clinical observations of persistent GI infection in COVID-19 patients. Ectopic expression of viral receptors revealed that the levels of angiotensin-converting enzyme 2 (ACE2) expression confer permissiveness to SARS-CoV-2 infection, and TMPRSS2 greatly facilitates ACE2-mediated SARS-CoV-2 dissemination. Interestingly, ACE2 but not TMPRSS2 expression was significantly promoted by enterocytic differentiation, suggesting that the state of enterocytic differentiation may serve as a determining factor for viral propagation. Thus, our study sheds light on the pathogenesis of SARS-CoV-2 in the GI tract.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/virologia , Mucosa Intestinal/virologia , Pneumonia Viral/virologia , Betacoronavirus/genética , Linhagem Celular , Infecções por Coronavirus/genética , Infecções por Coronavirus/metabolismo , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/virologia , Humanos , Mucosa Intestinal/metabolismo , Pandemias , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/genética , Pneumonia Viral/metabolismo , Receptores Virais/genética , Receptores Virais/metabolismo , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo
5.
Life Sci ; 261: 118460, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32961234

RESUMO

AIMS: The hyperpermeability of gut-vascular barrier (GVB) plays a role in gut-derived sepsis. The goal of this study was to evaluate if berberine might improve hepatic apolipoprotein M (ApoM) generation and raise plasma ApoM level to protect the compromised GVB. MATERIALS AND METHODS: The compromised GVB was induced by sepsis. Hepatic ApoM mRNA and phosphoenolpyruvate carboxykinase (PEPCK) mRNA and plasma ApoM level were assayed by qRT-PCR and ELISA, respectively. The permeability of intestinal capillary in vivo and of rat intestinal microvascular endothelial cells (RIMECs) in vitro was assayed by FITC-dextran. The blood glucose was detected by a glucometer. Plasma insulin, TNF-α and IL-1ß were assayed by ELISA. The plasmalemma vesicle-associated protein-1 (PV1), ß-catenin and occludin in RIMECs were assayed by Western blot. KEY FINDINGS: Sepsis decreased hepatic ApoM mRNA and plasma ApoM level, but raised hepatic PEPCK mRNA and plasma glucose, insulin, TNF-α, and IL-1ß levels. The increased vascular endothelial permeability was abrogated by recombinant rat ApoM in vivo or ApoM-bound S1P in vitro. ApoM-bound S1P decreased PV1 but increased occludin and ß-catenin expression in LPS-treated RIMECs. Berberine in a dose-dependent manner raised hepatic ApoM mRNA and plasma ApoM level, but decreased septic hyperglycemia, insulin resistance and plasma TNF-α and IL-1ß levels. Berberine reduced sepsis-induced PEPCK and TLR4 mRNA overexpression in the liver. SIGNIFICANCE: This study demonstrated berberine inhibited TLR4-mediated hyperglycemia, insulin resistance and proinflammatory molecule production, thereby increasing ApoM gene expression and plasma ApoM. Berberine protected the damaged GVB via modulation of ApoM/S1P pathway.


Assuntos
Apolipoproteínas M/metabolismo , Berberina/uso terapêutico , Permeabilidade Capilar/efeitos dos fármacos , Lisofosfolipídeos/metabolismo , Sepse/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Esfingosina/análogos & derivados , Animais , Berberina/farmacologia , Modelos Animais de Doenças , Trato Gastrointestinal/irrigação sanguínea , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/fisiopatologia , Células Hep G2 , Humanos , Masculino , Ratos Wistar , Sepse/metabolismo , Sepse/fisiopatologia , Esfingosina/metabolismo
6.
PLoS One ; 15(9): e0236724, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32956406

RESUMO

Aquaporins (AQP) are a family of plasma membrane proteins responsible for water transport through cell membranes. They are differentially expressed in different parts of the alimentary canal of insects where they regulate water transport. These proteins have been studied in detail in some insects, but few data are available for aquaporins of the honey bee, Apis mellifera. We used quantitative PCR to study the expression of six putative aquaporin genes in forager honey bees. We found differential expression of all putative AQP genes in crop, midgut, ileum, rectum and Malpighian tubules. We found the entomoglyceroporin Am_Eglp 1 expressed at extremely high levels in the midgut. We performed a functional characterization of Am_Eglp 1 using heterologous expression in Xenopus laevis oocyte followed by water uptake assays. Our results confirmed that the Am_Eglp 1 gene encodes a functional water transporter. This study shows that all putative honey bee aquaporin genes have complex expression patterns in the digestive and excretory organs of honey bee workers. Our results suggest that Am_Eglp 1 is the principal water transporter in the midgut of A. mellifera workers.


Assuntos
Aquaporinas/metabolismo , Abelhas/metabolismo , Trato Gastrointestinal/metabolismo , Proteínas de Insetos/metabolismo , Animais , Aquaporinas/genética , Abelhas/genética , Genes de Insetos , Proteínas de Insetos/genética , Oócitos , Xenopus laevis
7.
J Food Sci ; 85(9): 2923-2932, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32839962

RESUMO

Benzyl isothiocyanate (BITC) was encapsulated in oil-in-water emulsions stabilized by Pseudosciaena crocea roe protein isolate (PRPI). The stability, lipid digestion, BITC bioavailability, and retention rate of the emulsions were characterized using a simulated gastrointestinal tract model. Tween-corn and PRPI-medium-chain triglycerides (MCT) emulsions were used as controls. The membrane permeability and BITC absorption from these emulsions were investigated by in situ single-pass intestinal perfusion. The results showed that the PRPI-stabilized emulsions were stable under nonacidic environment conditions. Moreover, the PRPI-corn emulsion had more obvious protective effects than PRPI-MCT and Tween-corn emulsions. Atomic force and confocal laser scanning microscopy images showed that the protein hydrolyzed and oil droplets aggregated during simulated gastric phase digestion. Following the exposure of oil droplets in the small intestine phase, the PRPI-corn emulsion had a high rate of free fatty acid release (99.13 ± 2.49%), and the retention rate and bioavailability of BITC from the PRPI-corn emulsion were 75.93 ± 7.17% and 77.32 ± 5.36%, respectively, which were significantly higher than those measured for the other emulsions (P < 0.05). Moreover, the Ka and Peff of the PRPI-corn emulsion reached the maximum value at 45 min and then decreased slowly. These results suggest that the PRPI-corn emulsion delivery system is effective in encapsulating, delivering, and protecting BITC. PRACTICAL APPLICATION: This study provides some useful information for the food industry to develop a Pseudosciaena crocea roe protein isolate (PRPI) emulsion that could be successfully used to construct a BITC delivery system and improve benzyl isothiocyanate (BITC) bioavailability. The protective effect on BITC assessed in vitro simulated gastrointestinal tract and in situ single-pass intestinal perfusion are discussed.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Proteínas de Peixes/química , Mucosa Intestinal/metabolismo , Isotiocianatos/química , Animais , Disponibilidade Biológica , Digestão , Sistemas de Liberação de Medicamentos/instrumentação , Emulsões/química , Emulsões/metabolismo , Proteínas de Peixes/metabolismo , Trato Gastrointestinal/metabolismo , Humanos , Hidrólise , Isotiocianatos/metabolismo , Tamanho da Partícula , Perciformes , Triglicerídeos/química , Triglicerídeos/metabolismo , Zea mays/química
8.
Mol Immunol ; 126: 65-72, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32768860

RESUMO

The insect gut participates in initial local immune responses by producing reactive oxygen and nitrogen species as well as anti-microbial peptides to resist pathogenic invasions. Nitric oxide (NO), a signaling and an immune effector molecule synthesized by the enzyme NO synthase (NOS), mediates an early step of the signal transduction pathway. In this study, we evaluated NO levels after Nosema pernyi infection in Antheraea pernyi gut. NOS activity was higher in the microsporidia-infected gut of A. pernyi than in that of control. Three NOS-related genes were cloned, and their spatio-temporal expression patterns were evaluated. ApNOS2 was expressed quickly in the midgut after N. pernyi infection. Sodium nitroprusside, dihydrate (SNP), or Nω-L-nitro-arginine methyl ester, hydrochloride (L-NAME), altered the NO content in A. pernyi midgut. Anti-microbial peptides (AMPs) in the groups exposed to N. pernyi plus SNP and N. pernyi plus L-NAME exhibited higher and lower expression, respectively, relative to the control. These results indicate that microsporidia infection triggers short-term activation of NO and NOS genes in the A. pernyi gut that is downregulated after 24 h. Notably, infection rates can be influenced by a NOS inhibitor. Furthermore, NO can be induced by pathogens. Similarly, NO content in the A. pernyi gut also influences AMPs in humoral immunity and some immune-related genes. Our results suggest that nitric oxide plays a vital role in A. pernyi gut immunity.


Assuntos
Trato Gastrointestinal/imunologia , Microsporidiose/veterinária , Mariposas/imunologia , Óxido Nítrico/metabolismo , Nosema/imunologia , Animais , Peptídeos Catiônicos Antimicrobianos/metabolismo , Proteínas de Artrópodes/antagonistas & inibidores , Proteínas de Artrópodes/metabolismo , Regulação para Baixo , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Imunidade Humoral/efeitos dos fármacos , Imunidade nas Mucosas/efeitos dos fármacos , Microsporidiose/imunologia , Mariposas/enzimologia , Mariposas/microbiologia , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Análise Espaço-Temporal
9.
PLoS Genet ; 16(8): e1008941, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32760060

RESUMO

Apolipoprotein B-containing lipoproteins (B-lps) are essential for the transport of hydrophobic dietary and endogenous lipids through the circulation in vertebrates. Zebrafish embryos produce large numbers of B-lps in the yolk syncytial layer (YSL) to move lipids from yolk to growing tissues. Disruptions in B-lp production perturb yolk morphology, readily allowing for visual identification of mutants with altered B-lp metabolism. Here we report the discovery of a missense mutation in microsomal triglyceride transfer protein (Mtp), a protein that is essential for B-lp production. This mutation of a conserved glycine residue to valine (zebrafish G863V, human G865V) reduces B-lp production and results in yolk opacity due to aberrant accumulation of cytoplasmic lipid droplets in the YSL. However, this phenotype is milder than that of the previously reported L475P stalactite (stl) mutation. MTP transfers lipids, including triglycerides and phospholipids, to apolipoprotein B in the ER for B-lp assembly. In vitro lipid transfer assays reveal that while both MTP mutations eliminate triglyceride transfer activity, the G863V mutant protein unexpectedly retains ~80% of phospholipid transfer activity. This residual phospholipid transfer activity of the G863V mttp mutant protein is sufficient to support the secretion of small B-lps, which prevents intestinal fat malabsorption and growth defects observed in the mttpstl/stl mutant zebrafish. Modeling based on the recent crystal structure of the heterodimeric human MTP complex suggests the G865V mutation may block triglyceride entry into the lipid-binding cavity. Together, these data argue that selective inhibition of MTP triglyceride transfer activity may be a feasible therapeutic approach to treat dyslipidemia and provide structural insight for drug design. These data also highlight the power of yolk transport studies to identify proteins critical for B-lp biology.


Assuntos
Proteínas de Transporte/genética , Lipídeos/genética , Lipoproteínas/genética , Triglicerídeos/genética , Animais , Fígado Gorduroso/genética , Fígado Gorduroso/patologia , Trato Gastrointestinal/metabolismo , Humanos , Imunoprecipitação , Gotículas Lipídicas/metabolismo , Lipoproteínas/metabolismo , Mutação de Sentido Incorreto/genética , Mutação Puntual/genética , Transporte Proteico/genética , Triglicerídeos/metabolismo , Peixe-Zebra/genética
10.
J Anim Sci ; 98(7)2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32607561

RESUMO

The study was conducted to determine the effects of high levels of phytase on growth performance, nutrient digestibility, phytate breakdown, and expression of mucosal tight junction and nutrient transporter genes in weanling pigs. A total of 128 barrows were penned in groups of four and used in a randomized completely block design and assigned to four treatments for a 28-d study. A two-phase feeding was implemented (phase 1: day 1 to 14; phase 2: day 15 to 28). The diets differed in dietary calcium (Ca) and phosphorus (P) levels (positive control [PC]: 8.1 to 7.1 g/kg Ca and 6.5 to 6.8 g/kg P; negative control [NC]: 6.6 to 5.5 g/kg Ca and 5.6 to 5.3 g/kg P) from phase 1 to phase 2, respectively. NC diets were supplemented with phytase at 0 (NC), 1,500 (NC + 1,500), or 3,000 (NC + 3,000) phytase units (FTU)/kg. Blood was collected after fasting (day 27) or feeding (day 28) for the measurement of plasma inositol concentrations. On day 28, two pigs per pen were euthanized. Duodenal-jejunal and ileal digesta samples and feces were collected to determine inositol phosphates (InsP3-6) concentrations. Phytase supplementation increased the body weight on days 14 and 28 (P < 0.05). Average daily gain and feed efficiency compared with NC were increased by phytase with the majority of its effect in phase 1 (P < 0.05). The apparent ileal digestibility and apparent total tract digestibility of P were increased in piglets fed phytase-supplemented diets (P < 0.01) compared with NC piglets. Disappearance of InsP6 and total InsP3-6 up to the duodenum-jejunum, ileum, and in feces was increased by both phytase application rates (P < 0.01). Plasma concentrations of myo-inositol were higher (P < 0.001) in the phytase-supplemented diets than PC and NC diets, irrespective of whether pigs were fed or fasted. Expression of claudin 3 was higher in pigs fed both phytase-supplemented diets in the duodenum and jejunum compared with PC and NC. Mucin 2 expression was lower in the ileum of NC + 3,000 fed piglets compared with PC (P < 0.05), whereas expression of GLUT2 (solute carrier family 2-facilitated glucose transporter member 2) was increased (P < 0.05) by the NC + 3,000 treatment in all sections. In summary, high phytase supplementation increased the growth performance of nursery pigs. The increased expression of GLUT2 by phytase may indicate an upregulation of glucose absorption from the intestine by phytase.


Assuntos
6-Fitase/farmacologia , Digestão/efeitos dos fármacos , Suínos/fisiologia , Proteínas de Junções Íntimas/metabolismo , Junções Íntimas/genética , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Cálcio na Dieta/metabolismo , Dieta/veterinária , Suplementos Nutricionais , Digestão/fisiologia , Fezes , Trato Gastrointestinal/metabolismo , Íleo/metabolismo , Inositol/administração & dosagem , Masculino , Nutrientes , Fósforo/metabolismo , Fósforo na Dieta/metabolismo , Ácido Fítico/metabolismo , Proteínas de Junções Íntimas/genética , Junções Íntimas/metabolismo
11.
Korean J Gastroenterol ; 76(1): 4-8, 2020 07 25.
Artigo em Inglês, Coreano | MEDLINE | ID: mdl-32703914

RESUMO

The World Health Organization (WHO) declared the worldwide pandemic of Coronavirus disease-2019 (COVID-19) On March 11, 2020, just three months after the first outbreak of COVID-19 caused by Severe Acute Respiratory Syndrome Coronavirus 2 in China in December 2019. COVID-19 is a contagious disease that can affect anyone, anytime, anywhere, and has had a huge impact on our lives, including social, economic, educational, and cultural life. In this paper, I would like to explore the issues related to COVID-19 in the gastroenterology and share the experiences of domestic and overseas gastroenterologists, and ultimately to seek ways to effectively prepare for and cope with the pandemic era of COVID-19.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/patologia , Gastroenterologistas/psicologia , Pneumonia Viral/patologia , Betacoronavirus/isolamento & purificação , Betacoronavirus/metabolismo , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Endoscopia do Sistema Digestório , Trato Gastrointestinal/metabolismo , Humanos , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/transmissão , Pneumonia Viral/virologia
12.
Am J Physiol Gastrointest Liver Physiol ; 319(2): G245-G252, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32639848

RESUMO

In addition to the typical respiratory response, new coronavirus disease 2019 (COVID-19) is also associated with very common gastrointestinal symptoms. Cases with gastrointestinal symptoms are more likely to be complicated by liver injury and acute respiratory distress syndrome (ARDS). If not treated in time, coma and circulatory failure may ensue. As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects the human body through the combination of angiotensin-converting enzyme 2 (ACE2) in the gastrointestinal tract, the mechanism underlying the gastrointestinal symptoms may involve damage to the intestinal mucosal barrier and promotion of the production of inflammatory factors. Indeed, after cells in the lungs become infected by SARS-CoV-2, effector CD4+ T cells reach the small intestine through the gut-lung axis, causing intestinal immune damage and diarrhea; early extensive use of antibacterial and antiviral drugs can also lead to diarrhea in patients. Thus, treatment options for COVID-19 patients should be promptly adjusted when they have gastrointestinal symptoms. As SARS-CoV-2 has been detected in the feces of COVID-19 patients, future prevention and control efforts must consider the possibility of fecal-oral transmission of the virus.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus , Gastroenteropatias , Trato Gastrointestinal , Pandemias , Pneumonia Viral , Antivirais/farmacologia , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Gastroenteropatias/epidemiologia , Gastroenteropatias/fisiopatologia , Gastroenteropatias/terapia , Gastroenteropatias/virologia , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/fisiopatologia , Trato Gastrointestinal/virologia , Humanos , Incidência , Controle de Infecções/métodos , Pandemias/prevenção & controle , Seleção de Pacientes , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/metabolismo , Pneumonia Viral/fisiopatologia , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão
13.
PLoS One ; 15(7): e0236133, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32687546

RESUMO

BACKGROUND: Laparoscopic sleeve gastrectomy (SG) has surpassed Roux-en-Y gastric bypass (RYGB) as the most prevalent bariatric procedure worldwide. While RYGB and SG demonstrate equivalent short-term weight loss, long-term weight loss tends to be greater after RYGB. Differences in the effect of these procedures on gastrointestinal hormones that regulate energy homeostasis are felt to partially underlie differences in outcomes. The objective of this study was to prospectively quantify blood levels of gut hormones of energy and glucose homeostasis at one year follow up to delineate possible reasons for greater efficacy of RYGB over SG in achieving weight loss. METHODS: Patients undergoing SG (n = 19) and RYGB (n = 40) were studied before surgery and at 2,12, 26, and 52 weeks postoperatively. Blood samples drawn in the fasted state and after a liquid mixed meal were assayed at baseline, 26, and 52 weeks for peptide YY (PYY), glucagon-like peptide-1 (GLP-1), ghrelin, insulin, glucose, and leptin. Fasting and postprandial appetitive sensations were assessed by visual analog scale. RESULTS: At 1 year there was greater weight loss in RYGB compared with SG patients (30% vs 27%; P = 0.03). Area under the curve (AUC) after the mixed meal for PYY was greater in RYGB patients (P<0.001). RYGB patients had significant increases in GLP-1 AUC compared to baseline (P = 0.002). Ghrelin levels decreased only after SG compared to baseline (P<0.001) but were not significantly different from RYGB. There was a trend toward decreased sweet cravings in RYGB patients (P = 0.056). CONCLUSIONS: Differences in gastrointestinal hormones that regulate energy and glucose homeostasis are a possible mechanism for greater efficacy of RYGB compared to SG.


Assuntos
Gastrectomia , Derivação Gástrica , Trato Gastrointestinal/metabolismo , Hormônios/sangue , Laparoscopia , Adulto , Idoso , Glicemia/metabolismo , Feminino , Homeostase , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
14.
J Anim Sci ; 98(6)2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32498088

RESUMO

An experiment was conducted during the winter of two consecutive years to evaluate the effects of feeding green-chopped cool-season forages on digestibility, ruminal fermentation, and blood parameters in beef steers. Nine ruminally cannulated Angus crossbred steers (year 1: 359 ± 79 kg; year 2: 481 ± 105 kg) received ad libitum green-chopped forages from pastures planted with one of the following mixtures: 1) OAT = Horizon 201 oats (Avena sativa L.)/Prine annual ryegrass (Lolium multiflorum Lam.) at 95 and 17 kg/ha, respectively; 2) RYE = FL401 cereal rye (Secale cereale L.)/Prine annual ryegrass (Lolium multiflorum Lam.) at 78 and 17 kg/ha, respectively; or 3) TRIT = Trical 342 triticale (X Triticosecale spp.)/Prine annual ryegrass (Lolium multiflorum Lam.) at 95 and 17 kg/ha, respectively. Intake was measured using the GrowSafe system and orts were discarded prior to subsequent feeding. After a 14-d adaptation, feed and fecal samples were collected twice daily for 4 d to determine apparent total tract nutrient digestibility using indigestible neutral detergent fiber (NDF) as an internal marker. On day 19, blood and ruminal fluid samples were collected every 3 h during a 24-h period to analyze plasma urea nitrogen (PUN) and glucose, ruminal pH, and concentration of ruminal ammonia nitrogen (NH3-N) and volatile fatty acids (VFA). Data were analyzed as a generalized randomized block design with repeated measures using the PROC MIX of SAS. No effect of treatment (P > 0.05) was observed for intake of dry matter, organic matter (OM), crude protein, NDF, or acid detergent fiber. Apparent total tract digestibility of nutrients was greater (P < 0.05) for OAT and TRIT when compared with RYE, with OM digestibility being 82.7%, 79.6%, and 69.5%, respectively. An effect of time (P < 0.01) was observed for ruminal pH. Plasma concentration of glucose was greater (P < 0.01) in steers consuming OAT, whereas steers fed RYE had greater (P < 0.05) concentrations of ruminal NH3-N and PUN, and the least concentration of total ruminal VFA (P < 0.05), despite having the greatest (P > 0.05) molar proportion of acetate, branched-chain VFA, and acetate:propionate. Increased nutrient digestibility and favorable ruminal fermentation and blood metabolites of OAT and TRIT are potentially conducive to enhanced growth performance when compared with RYE.


Assuntos
Ração Animal/análise , Bovinos/fisiologia , Fibras na Dieta/metabolismo , Nitrogênio/metabolismo , Animais , Avena , Bovinos/sangue , Digestão , Ácidos Graxos Voláteis/metabolismo , Fezes/química , Fermentação , Trato Gastrointestinal/metabolismo , Masculino , Nutrientes/metabolismo , Rúmen/metabolismo , Estações do Ano
15.
J Anim Sci ; 98(7)2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32564063

RESUMO

AbstractThree experiments were conducted to test the hypothesis that standardized ileal digestibility (SID) of amino acids (AA), concentration of metabolizable (ME), and standardized total tract digestibility (STTD) of P in a new source of distillers dried grains with solubles (DDGS; ProCap DDGS) are greater than in conventional de-oiled DDGS. In experiment 1, nine barrows (initial BW: 67.2 ± 6.4 kg) with a T-cannula in the distal ileum were allotted to a triplicated 3 × 3 Latin square design with three diets and three periods for a total of nine replicate pigs per diet. Two diets included ProCap DDGS or de-oiled DDGS as the sole source of crude protein (CP) and AA. An N-free diet was used to determine the basal endogenous losses of CP and AA. Ileal digesta were collected on days 5 and 6 of each period after 4 d of adaptation to diets. Results from experiment 1 indicated that ProCap DDGS contained more CP and AA compared with de-oiled DDGS. The SID of all AA in ProCap DDGS was greater (P < 0.001) compared with de-oiled DDGS with the exception that the SID of Pro was not different between the two sources of DDGS. In experiment 2, 24 growing barrows (initial BW: 32.7 ± 3.1 kg) were housed individually in metabolism crates and used in a randomized complete block design and fed a corn-based diet or two diets containing corn and each source of DDGS with eight replicate pigs per diet. Fecal and urine samples were collected for 4 d after 7 d of adaptation. Results from experiment 2 indicated that concentration of ME in ProCap DDGS was greater (P < 0.05) compared with corn or de-oiled DDGS. In experiment 3, 32 growing barrows (initial BW: 20.2 ± 0.9 kg) were placed in metabolism crates and allotted to four diets with eight pigs per diet using a 2 × 2 factorial treatment arrangement. The de-oiled DDGS and ProCap DDGS were both included in a diet without microbial phytase and a diet with microbial phytase (500 units/kg diet). Pigs were adapted to the diets for 5 d and fecal samples were collected for 4 d. Results from experiment 3 indicated that inclusion of phytase in the diet containing ProCap DDGS increased (P < 0.05) the STTD of P, but addition of phytase to the de-oiled DDGS diet did not increase STTD of P (interaction, P < 0.001), but the STTD of P was greater (P < 0.05) in de-oiled DDGS compared with ProCap DDGS. In conclusion, ProCap DDGS has greater SID of AA and contains more ME, but has reduced STTD of P compared with conventional de-oiled DDGS.


Assuntos
Aminoácidos/metabolismo , Ração Animal/análise , Dieta/veterinária , Digestão/fisiologia , Fósforo/metabolismo , Suínos/fisiologia , 6-Fitase/metabolismo , Fenômenos Fisiológicos da Nutrição Animal , Animais , Fezes/química , Trato Gastrointestinal/metabolismo , Íleo/metabolismo , Masculino , Zea mays/química
16.
J Anim Sci ; 98(6)2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32497185

RESUMO

The outer cell wall of yeast is characterized by high levels of ß-glucans and mannan-oligosaccharides (MOS), which have been linked with beneficial effects on intestinal health and immune status in dogs. In this study, a standardized in vitro simulation of the canine gastrointestinal tract (Simulator of the Canine Intestinal Microbial Ecosystem; SCIME) was used to evaluate the effect of a Saccharomyces cerevisiae-based product, consisting of 27.5% ß-glucans and 22.5% MOS, on the activity (as assessed by measurement of fermentative metabolites) and composition (as assessed by 16S-targeted Illumina sequencing) of canine intestinal microbiota. The S. cerevisiae-based product was tested at three different dosages, i.e., 0.5, 1.0, and 2.0 g/d. A dose-dependent fermentation pattern was observed along the entire length of the colon, as shown by the increased production of the health-related acetate, propionate, and butyrate for the three concentrations tested (0.5, 1.0, and 2.0 g/d). A consistent finding for all three tested concentrations was the increased propionate production (P < 0.05) in the simulated proximal and distal colon. These changes in terms of fermentative metabolites could be linked to specific microbial alterations at the family level, such as the specific stimulation of the propionate-producing families Porphyromonadaceae and Prevotellaceae upon in vitro exposure to the S. cerevisiae-based product. Other consistent changes in community composition upon repeated exposure included the decrease in the Enterobacteriaceae and the Fusobacteriaceae families, which both contain several potentially opportunistic pathogens. Altogether, the generated data support a possible health-promoting role of a product high in ß-glucans and MOS when supplemented to the dogs' diet.


Assuntos
Suplementos Nutricionais/análise , Cães/fisiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Mananas/farmacologia , Oligossacarídeos/farmacologia , Saccharomyces cerevisiae/química , beta-Glucanas/farmacologia , Animais , Parede Celular/química , Dieta/veterinária , Cães/microbiologia , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/crescimento & desenvolvimento , Fermentação , Fusobactérias/efeitos dos fármacos , Fusobactérias/crescimento & desenvolvimento , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Fermento Seco/química
17.
Chemosphere ; 251: 126632, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32443225

RESUMO

Flame retardants (FRs) from electronic waste (e-waste) are a widespread environmental concern. In our study, in vitro physiologically based extraction tests (PBETs) for FRs were conducted in three different areas where dust remained after processing of e-waste to identify the bioaccessible FRs and quantify their bioaccessibilities of gastrointestinal tract for human as well as to assess the exposure via ingestion of workers in e-waste processing workshops. All 36 FRs were measured and detected in indoor dusts. Among the FRs, the mean concentrations of polybrominated diphenyl ethers (PBDEs) in the floor dust and settled dust were highest, 65,000 ng/g, and 31,000 ng/g, respectively. In contrast, phosphorus-containing flame retardants (PFRs) presented the highest mean concentration in the workplace dust samples, 64,000 ng/g. However, the highest bioaccessible concentrations in workplace dust, floor dust, and settled dust were observed for PFRs: 5900, 1600, and 680 ng/g, respectively. This study revealed that the higher bioaccessibility of PFRs versus other compounds was related to the negative correlation between FR concentrations and log KOW (hydrophobicity) values. The fact that hazard indices calculated using measured bioaccessibilities were less than 1 suggested that the non-cancer risk to human health by the FRs exposure via dust ingestion might be low.


Assuntos
Poeira/análise , Resíduo Eletrônico/análise , Retardadores de Chama/análise , Éteres Difenil Halogenados/análise , Exposição Ocupacional/análise , Poluição do Ar em Ambientes Fechados/análise , Disponibilidade Biológica , Ingestão de Alimentos , Monitoramento Ambiental , Trato Gastrointestinal/metabolismo , Humanos , Modelos Biológicos , Medição de Risco , Vietnã
18.
Nat Biomed Eng ; 4(5): 560-571, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32393891

RESUMO

The oral administration of peptide drugs is hampered by their metabolic instability and limited intestinal uptake. Here, we describe a method for the generation of small target-specific peptides (less than 1,600 Da in size) that resist gastrointestinal proteases. By using phage display to screen large libraries of genetically encoded double-bridged peptides on protease-resistant fd bacteriophages, we generated a peptide inhibitor of the coagulation Factor XIa with nanomolar affinity that resisted gastrointestinal proteases in all regions of the gastrointestinal tract of mice after oral administration, enabling more than 30% of the peptide to remain intact, and small quantities of it to reach the blood circulation. We also developed a gastrointestinal-protease-resistant peptide antagonist for the interleukin-23 receptor, which has a role in the pathogenesis of Crohn's disease and ulcerative colitis. The de novo generation of targeted peptides that resist proteolytic degradation in the gastrointestinal tract should help the development of effective peptides for oral delivery.


Assuntos
Peptídeos/administração & dosagem , Peptídeos/uso terapêutico , Proteólise , Administração Oral , Sequência de Aminoácidos , Animais , Técnicas de Visualização da Superfície Celular , Cristalografia por Raios X , Feminino , Trato Gastrointestinal/metabolismo , Humanos , Isomerismo , Camundongos Endogâmicos BALB C , Modelos Moleculares , Peptídeo Hidrolases/metabolismo , Biblioteca de Peptídeos , Peptídeos/química , Estabilidade Proteica , Estrutura Secundária de Proteína , Receptores de Interleucina/antagonistas & inibidores , Receptores de Interleucina/metabolismo
19.
Ecotoxicol Environ Saf ; 200: 110745, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32460051

RESUMO

Chronic dietary bioaccumulation tests with rodents are required for new substances, including engineered nanomaterials (ENMs), in order to provide information on the potential hazards to human health. However, screening tools are needed to manage the diversity of ENMs and alternative methods are desirable with respect to animal welfare. Here, an ex vivo gut sac method was used to estimate the dietary bioaccumulation potential of silver nanomaterials. The entire gastrointestinal tract (except the caecum) was removed and filled with a gut saline containing 1 mg L-1 of Ag as either AgNO3, silver nanoparticles (Ag NPs) or silver sulphide nanoparticles (Ag2S NPs), and compared to controls with no added Ag. The gut sacs were incubated for 4 h, rinsed to remove excess media, and the total Ag determined in the mucosa and muscularis. There was no detected Ag in the control treatments. Within the Ag treatments, 1.4-22% of the exposure dose was associated with the tissues and serosal saline. Within the mucosa of the AgNO3 treatment, the highest Ag concentration was associated with the intestinal regions (3639-7087 ng g-1) compared to the stomach (639 ± 128 ng g-1). This pattern was also observed in the Ag NP and Ag2S NP treatments, but there was no significant differences between any Ag treatments for the mucosa. However, differences between treatments were observed in the muscularis concentration. For example, both the Ag NP (907 ± 284 ng g -1) and Ag2S NP (1482 ± 668 ng g-1) treatments were significantly lower compared to the AgNO3 treatment (2514 ± 267 ng g-1). The duodenum demonstrated serosal accumulation in both the AgNO3 (~10 ng mL-1) and Ag NP (~3 ng mL-1) treatments. The duodenum showed some of the highest Ag accumulation with 41, 61 and 57% of the total Ag in the mucosa compared to the muscularis for the AgNO3, Ag NP and Ag2S NP treatments, respectively. In conclusion, the ex vivo gut sac method demonstrates the uptake of Ag in all Ag treatments, with the duodenum the site of highest accumulation. Based on the serosal saline accumulation, the ranked order of accumulation is AgNO3 > Ag NPs > Ag2S NPs.


Assuntos
Trato Gastrointestinal/metabolismo , Nanopartículas Metálicas , Compostos de Prata/metabolismo , Nitrato de Prata/metabolismo , Prata/metabolismo , Animais , Bioacumulação , Dieta , Intestinos , Membrana Mucosa/metabolismo , Ratos Wistar , Estômago
20.
Yakugaku Zasshi ; 140(5): 599-608, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32378658

RESUMO

Although oral drugs account for 80% of the world drug market, many difficulties arise in their development. The drug absorption profile after oral administration may be influenced by multiple factors, including dosing conditions and physiological state of the gastrointestinal (GI) tract. Variability in GI fluid volume may influence the absorption characteristics. Indeed, the contributions of passive diffusion, transporters, and metabolic enzymes depend on GI drug concentration, which is influenced by changes in GI fluid volume. However, this important variable has been neglected in many prediction methods for oral drug absorption and drug interactions, and for convenience it is often assumed that the GI water volume is fixed at a constant value. Major global regulatory agencies such as the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA), and Japanese Pharmaceuticals and Medical Devices Agency (PMDA) recommend using a constant fluid volume of 250 mL (the fluid volume of a glass of water) to estimate the theoretical GI concentration of drugs after oral administration. However, the actual volume of water in the GI tract is both time- and site-dependent as a result of water intake, absorption, secretion, and GI transit. This review article summarizes our data showing that luminal water volume is influenced by the osmolality of the applied solution, and illustrates how this effect may contribute to changes in GI drug concentration, resulting in altered drug absorption.


Assuntos
Interações Medicamentosas , Trato Gastrointestinal/metabolismo , Absorção Intestinal , Preparações Farmacêuticas/administração & dosagem , Preparações Farmacêuticas/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Administração Oral , Água Corporal/metabolismo , Humanos , Modelos Biológicos , Concentração Osmolar , Valor Preditivo dos Testes
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