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1.
Zhonghua Wei Chang Wai Ke Za Zhi ; 22(11): 1095-1100, 2019 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-31770844

RESUMO

Colonic organoids are three-dimensional organotypic cultures of the colonic stem cells or pluripotent stem cells. Its essence is the culture of colonic stem cells or pluripotent stem cells, and their derived intestinal epithelial cells, intestinal endocrine cells and goblet cells in basement membrane extract with specific growth factors. Colonic organoids are comprised of all major types of colonic epithelial cells and represent the architecture and function remarkably similar to those of the colonic epithelium, faithfully recapitulating the functional colonic epithelium ex vivo. As a superior basic experimental model, colonic organoids are representing advantages over conventional cell models and animal models in many aspects, such as high successful rate, short productive cycle, and high consistency with source tissue. Since first reported in 2011, colonic organoids have soon become an important topic in the field of colonic diseases. It has now been applied in the field of physiology of colonic epithelium, infectious diarrhea, ulcerative colitis, regeneration of intestinal injury, and colon tumors. In this review, we summarize the research advances of establishment and application of colonic organoids.


Assuntos
Colo/fisiologia , Mucosa Intestinal/fisiologia , Organoides/fisiologia , Células-Tronco/fisiologia , Animais , Colo/citologia , Humanos , Intestinos
2.
Artigo em Inglês | MEDLINE | ID: mdl-31594645

RESUMO

The number of disorders now linked to increased intestinal mucosal permeability implies that a substantial percent of the population is affected. Drug interventions targeting reduced tight junctional permeability are being pursued. Although hyper-permeability in itself is not a clinically recognized disease entity, its relationship to disease processes has driven interest in measuring, and even monitoring mucosal permeability in vivo. Along with improved knowledge of gut barrier physiology, advances have been made in tests and biomarkers of barrier function. Drawing from our experiences in the past decade, considerations and challenges faced in assessing in vivo intestinal permeability are discussed herein, along with indications of what the future might hold.


Assuntos
Biomarcadores/metabolismo , Mucosa Intestinal/fisiologia , Intestinos/fisiopatologia , Permeabilidade , Humanos
3.
Nat Commun ; 10(1): 4368, 2019 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-31554819

RESUMO

The colonic epithelial turnover is driven by crypt-base stem cells that express the R-spondin receptor Lgr5. Signals that regulate epithelial regeneration upon stem cell injury are largely unknown. Here, we explore the dynamics of Wnt signaling in the colon. We identify two populations of cells with active Wnt signaling: highly proliferative Lgr5+/Axin2+ cells, as well as secretory Lgr5-/Axin2+ cells. Upon Lgr5+ cell depletion, these cells are recruited to contribute to crypt regeneration. Chemical injury induced by DSS leads to a loss of both Lgr5+ cells and Axin2+ cells and epithelial regeneration is driven by Axin2- cells, including differentiated Krt20+ surface enterocytes. Regeneration requires stromal Rspo3, which is present at increased levels upon injury and reprograms Lgr5- but Lgr4+ differentiated cells. In contrast, depletion of stromal Rspo3 impairs crypt regeneration, even upon mild injury. We demonstrate that Rspo3 is essential for epithelial repair via induction of Wnt signaling in differentiated cells.


Assuntos
Colo/fisiologia , Mucosa Intestinal/fisiologia , Regeneração/fisiologia , Células-Tronco/metabolismo , Trombospondinas/metabolismo , Animais , Proteína Axina/genética , Proteína Axina/metabolismo , Diferenciação Celular/genética , Colite/genética , Colite/metabolismo , Colo/metabolismo , Enterócitos/metabolismo , Perfilação da Expressão Gênica/métodos , Mucosa Intestinal/metabolismo , Queratina-20/genética , Queratina-20/metabolismo , Camundongos Knockout , Camundongos Transgênicos , Receptores Acoplados a Proteínas-G/genética , Receptores Acoplados a Proteínas-G/metabolismo , Regeneração/genética , Células-Tronco/citologia , Trombospondinas/genética , Via de Sinalização Wnt/genética
4.
Animal ; 13(11): 2736-2744, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31475667

RESUMO

Gaining a deeper understanding into the underlying mechanisms associated with intestinal function and immunity during the weaning transition is critical to help shed new light into applied nutrition approaches to improve piglet performance and health during this critical life-stage transition. The transient anorexia triggered at weaning leads to compromised intestinal barrier function and a localized inflammatory response. Considering barrier function, specific nutrient fractions appear to have a significant impact on the development and function of the immune and microbial systems around weaning. Understanding the specific impact of nutrients in the small intestine and hindgut is important for helping to bring more focus and consistency to nutritional approaches to support health and immunity during the weaning transition period. The challenge continues to be how to translate these modes of action into practical and scalable approaches for swine nutrition. We will focus specifically on practical nutritional approaches to influence intestinal immunity through lipid, protein and antioxidant nutrition.


Assuntos
Estado Nutricional/imunologia , Suínos/imunologia , Animais , Mucosa Intestinal/imunologia , Mucosa Intestinal/fisiologia , Intestinos/imunologia , Intestinos/fisiologia , Suínos/fisiologia , Desmame
5.
J Dairy Sci ; 102(9): 7697-7706, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31326167

RESUMO

Nutrition plays a crucial role in human gut health through the improvement of gut barrier functionality. Donkey milk represents an interesting source of natural antimicrobial factors such as lysozyme. Recently, anti-inflammatory properties of donkey milk lysozyme activity were described in a mouse model of ileitis. The current increase of donkey milk consumption highlights the necessity to propose a healthy milk compliant with microbiological standards. This study aims to define a heat treatment of donkey milk, retaining its high lysozyme activity, and to evaluate its beneficial effects on a gut barrier impairment model due to chronic stress in mice. To perform this experiment, samples of raw donkey milk were collected in 15 distinct French farms. Microbiological analysis and lysozyme content and activity were evaluated for each sample. Then, several heat treatments were carried out to define a time and temperature combination that allowed for both a reduction in the number of total micro-organisms, increasing the shelf-life of the product, and preservation of lysozyme activity. The beneficial effect of heated donkey milk on the gut barrier of mice was evaluated and compared with raw donkey milk. We found that samples of raw donkey milk showed low total mesophilic microbial counts, and no pathogens were detected. Among the different heat-treatment procedures tested, a 2-min, 72°C combination was determined to be the most optimal time and temperature combination to preserve lysozyme activity and increase the shelf-life of donkey milk. Oral administration of this heat-treated donkey milk in mice counteracted chronic stress-induced intestinal damage, illustrated by gut hyper-permeability and low-grade inflammation, similar to raw donkey milk. We have demonstrated for the first time that oral intervention with donkey milk, optimally heat-treated to retain enzymatic lysozyme activity, improves intestinal barrier damage linked to psychological stress in mice.


Assuntos
Equidae , Temperatura Alta , Mucosa Intestinal/fisiologia , Leite/enzimologia , Muramidase/metabolismo , Estresse Fisiológico/fisiologia , Animais , Anti-Inflamatórios , Aprendizagem da Esquiva , Manipulação de Alimentos/métodos , Humanos , Mucosa Intestinal/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Leite/microbiologia , Muramidase/farmacologia , Permeabilidade/efeitos dos fármacos , Água
6.
Bull Exp Biol Med ; 167(3): 380-383, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31346875

RESUMO

We present the results of analysis of skin epidermis thickness in individuals with recessive mutation c.-23+1G>A in the GJB2 gene in comparison with individuals without this mutation living in Eastern Siberia (Yakut population). We examined 152 individuals with different genotypes by GJB2 gene mutation c.-23+1G>A. Homozygotes and heterozygotes by c.-23+1G>A have thicker epidermal layer (0.245 mm and 0.269 mm, respectively) in comparison with individuals without this mutation (0.193 mm) (p<0.05). The obtained data support the hypothesis about selective advantage of carriers of mutant GJB2 gene alleles and partly explain extremely high carrier frequency (10.3%) of c.-23+1G>A mutation in the GJB2 gene in Yakut population in Eastern Siberia.


Assuntos
Conexinas/genética , Epiderme/fisiologia , Frequência do Gene/genética , Perda Auditiva Neurossensorial/genética , Adolescente , Adulto , Temperatura Baixa , Resistência à Doença/genética , Resistência à Doença/fisiologia , Feminino , Heterozigoto , Homozigoto , Humanos , Mucosa Intestinal/fisiologia , Masculino , Sibéria , Adulto Jovem
7.
Nature ; 571(7765): 398-402, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31292548

RESUMO

A decline in stem cell function impairs tissue regeneration during ageing, but the role of the stem-cell-supporting niche in ageing is not well understood. The small intestine is maintained by actively cycling intestinal stem cells that are regulated by the Paneth cell niche1,2. Here we show that the regenerative potential of human and mouse intestinal epithelium diminishes with age owing to defects in both stem cells and their niche. The functional decline was caused by a decrease in stemness-maintaining Wnt signalling due to production of Notum, an extracellular Wnt inhibitor, in aged Paneth cells. Mechanistically, high activity of mammalian target of rapamycin complex 1 (mTORC1) in aged Paneth cells inhibits activity of peroxisome proliferator activated receptor α (PPAR-α)3, and lowered PPAR-α activity increased Notum expression. Genetic targeting of Notum or Wnt supplementation restored function of aged intestinal organoids. Moreover, pharmacological inhibition of Notum in mice enhanced the regenerative capacity of aged stem cells and promoted recovery from chemotherapy-induced damage. Our results reveal a role of the stem cell niche in ageing and demonstrate that targeting of Notum can promote regeneration of aged tissues.


Assuntos
Envelhecimento , Senescência Celular , Esterases/metabolismo , Mucosa Intestinal/patologia , Celulas de Paneth/metabolismo , Regeneração , Envelhecimento/fisiologia , Animais , Senescência Celular/fisiologia , Esterases/antagonistas & inibidores , Esterases/biossíntese , Feminino , Humanos , Mucosa Intestinal/fisiologia , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , PPAR alfa/metabolismo , Celulas de Paneth/patologia , Receptores Acoplados a Proteínas-G/metabolismo , Nicho de Células-Tronco , Células-Tronco/patologia , Proteínas Wnt/antagonistas & inibidores , Via de Sinalização Wnt
8.
Curr Gastroenterol Rep ; 21(8): 34, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31289921

RESUMO

PURPOSE OF REVIEW: The gastroduodenal mucosal layer is a complex and dynamic system that functions in an interdependent manner to resist injury. We review and summarize the most updated knowledge about gastroduodenal defense mechanisms and specifically address (a) the mucous barrier, (b) membrane and cellular properties, and vascular, hormonal, and (c) gaseous mediators. RECENT FINDINGS: Trefoil factor family peptides play a crucial role in cellular restitution by increasing cellular permeability and expression of aquaporin channels, aiding cellular migration and tissue repair. Additionally, evidence suggests that the symptoms of functional dyspepsia may be attributed to alterations in the duodenum, including low-grade inflammation and increased mucosal permeability. The interaction of the various mucosal protective components helps maintain structural and functional homeostasis. There is increasing evidence suggesting that the upper GI microbiota plays a crucial role in the defense mechanisms. However, this warrants further investigation.


Assuntos
Duodeno/fisiologia , Mucosa Gástrica/fisiologia , Mucosa Intestinal/fisiologia , Duodeno/lesões , Duodeno/metabolismo , Mucosa Gástrica/lesões , Mucosa Gástrica/metabolismo , Microbioma Gastrointestinal/fisiologia , Humanos , Mucosa Intestinal/lesões , Mucosa Intestinal/metabolismo , Mucinas/fisiologia , Permeabilidade , Fatores de Proteção
9.
J Biomed Sci ; 26(1): 46, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-31189465

RESUMO

BACKGROUND: Triggering receptor expressed on myeloid cells-1 (TREM-1) is highly expressed on macrophages in inflamed intestines and reportedly promotes inflammatory bowel disease (IBD) by augmenting pro-inflammatory responses. To study the mechanism mediated by TREM-1 on macrophages, we generated an independent TREM-1 deficient mouse. METHODS: Acute colitis was induced in C57BL/6 and TREM-1-deficient mice by the administration of dextran sodium sulfate (DSS). Colonic lamina propria immune cell composition and cytokines were analyzed. An innate lymphoid cell (ILC) co-culture experiment with macrophages was used to analyze IL-22 levels. Exogenous IL-22 and TREM-1-expressing macrophages were supplied to TREM-1-deficient mice for examining their effects on intestinal barrier integrity. RESULTS: In inflamed colons, TREM-1 loss compromised the activation of ILC3 and their production of IL-22, which is required for intestinal barrier integrity. ILC3-mediated IL-22 production depends on IL-1ß secreted by M1-polarized macrophages, and we found that TREM-1 deficiency results in a decreased number of IL-1ß producing-M1 macrophages in colons exposed to DSS. Accordingly, DSS-mediated damage was ameliorated by supplying exogenous IL-22 and TREM-1-expressing macrophages to TREM-1-deficient mice. CONCLUSIONS: TREM-1 plays a crucial role in regulating IL-22 production by ILC3 through modulating M1-macrophage polarization during DSS-induced acute colitis.


Assuntos
Colite/patologia , Interleucinas/metabolismo , Mucosa Intestinal/fisiologia , Linfócitos/imunologia , Macrófagos/fisiologia , Receptor Gatilho 1 Expresso em Células Mieloides/metabolismo , Animais , Colite/induzido quimicamente , Colite/fisiopatologia , Sulfato de Dextrana/toxicidade , Mucosa Intestinal/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Knockout
11.
PLoS Comput Biol ; 15(5): e1006986, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31050663

RESUMO

Immunoglobulin A is a class of antibodies produced by the adaptive immune system and secreted into the gut lumen to fight pathogenic bacteria. We recently demonstrated that the main physical effect of these antibodies is to enchain daughter bacteria, i.e. to cross-link bacteria into clusters as they divide, preventing them from interacting with epithelial cells, thus protecting the host. These links between bacteria may break over time. We study several models using analytical and numerical calculations. We obtain the resulting distribution of chain sizes, that we compare with experimental data. We study the rate of increase in the number of free bacteria as a function of the replication rate of bacteria. Our models show robustly that at higher replication rates, bacteria replicate before the link between daughter bacteria breaks, leading to growing cluster sizes. On the contrary at low growth rates two daughter bacteria have a high probability to break apart. Thus the gut could produce IgA against all the bacteria it has encountered, but the most affected bacteria would be the fast replicating ones, that are more likely to destabilize the microbiota. Linking the effect of the immune effectors (here the clustering) with a property directly relevant to the potential bacterial pathogeneicity (here the replication rate) could avoid to make complex decisions about which bacteria to produce effectors against.


Assuntos
Aderência Bacteriana/imunologia , Microbioma Gastrointestinal/imunologia , Microbiota/imunologia , Animais , Bactérias/imunologia , Aderência Bacteriana/fisiologia , Fenômenos Fisiológicos Bacterianos , Fenômenos Biológicos , Simulação por Computador , Reagentes para Ligações Cruzadas , Homeostase/fisiologia , Humanos , Imunoglobulina A/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/fisiologia , Microbiota/fisiologia
12.
Biofabrication ; 11(4): 045001, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31091514

RESUMO

A new in vitro gut microfluidic chip that mimics in vivo intestinal canal morphology and stimulation is developed to contribute to research into tissue engineering, and intestinal development and function. This strategy utilizes centrifugation to configure spatial cells along the side wall of a vertical cylinder-like microfluidic chamber, by which a tubular intestinal epithelium cell sheet is formed. Diverse intestinal cell lines are inoculated to address this approach. Furthermore, to generate microenvironmental stimulation, low-level centrifugation introduces fluid flow to this microfluidic system perpendicularly acting on cell sheet cultivation for several days. Fluid flow engenders the sectional cell sheet to bend toward the cell chamber lumen, which manifests an intestinal epithelium vaulted and wrinkle morphology. This may mimic the fluid flow existing in in vivo material transportation and the absorption of the gut epithelium barrier. In addition, the same fluid flow stimulation was reproduced in another Transwell system, which also exhibited a wrinkle epithelium cell sheet. Under fluid flow stimulation, some of the villus specific genes' expression level increased in the microfluidics and Transwell insert. Thus, this new centrifugation configuring gut microfluidic chip may offer novel insights into the research of intestinal structure and function.


Assuntos
Intestinos/fisiologia , Dispositivos Lab-On-A-Chip , Engenharia Tecidual/métodos , Animais , Técnicas de Cultura de Células , Linhagem Celular , Centrifugação , Desenho de Equipamento , Regulação da Expressão Gênica , Humanos , Mucosa Intestinal/fisiologia , Mucosa Intestinal/ultraestrutura , Intestinos/ultraestrutura , Ratos , Reologia
13.
J Microbiol Biotechnol ; 29(6): 863-876, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31091863

RESUMO

Farm animals such as piglets are often affected by environmental stress, which can disturb the gut ecosystem. Antibiotics were commonly used to prevent diarrhea in weaned piglets, but this was banned by the European Union due to the development of antibiotic resistance. However, the use of probiotics instead of antibiotics may reduce the risk posed by pathogenic microorganisms and reduce the incidence of gastrointestinal diseases. Therefore, this study was conducted to investigate the effects of Lactobacillus casei Zhang on the mechanical barrier and immune function of early-weaned piglets infected using Escherichia coli K88 based on histomorphology and immunology. Fourteen-day-old weaned piglets were divided into a control group and experimental groups that were fed L. casei Zhang and infected with E. coli K88 with or without prefeeding and/or postfeeding of L. casei Zhang. The L. casei Zhang dose used was 107 CFU/g diet. Jejunum segments were obtained before histological, immunohistochemical, and western blot analyses were performed. In addition, the relative mRNA expression of toll receptors and cytokines was measured. Piglets fed L. casei Zhang showed significantly increased jejunum villus height, villus height-crypt depth ratio, muscle thickness, and expression of proliferating cell nuclear antigen and tight junction proteins ZO-1 and occludin. The use of L. casei Zhang effectively reduced intestinal inflammation after infection. We found that L. casei Zhang feeding prevented the jejunum damage induced by E. coli K88, suggesting that it may be a potential alternative to antibiotics for preventing diarrhea in early-weaned piglets.


Assuntos
Infecções por Escherichia coli/veterinária , Expressão Gênica/efeitos dos fármacos , Mucosa Intestinal/fisiologia , Jejuno/efeitos dos fármacos , Lactobacillus casei/fisiologia , Probióticos/administração & dosagem , Doenças dos Suínos/prevenção & controle , Animais , Citocinas/genética , Suplementos Nutricionais , Escherichia coli Enterotoxigênica/fisiologia , Infecções por Escherichia coli/patologia , Infecções por Escherichia coli/prevenção & controle , Fatores Imunológicos/genética , Fatores Imunológicos/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Jejuno/patologia , Ocludina/genética , Ocludina/metabolismo , Probióticos/farmacologia , Antígeno Nuclear de Célula em Proliferação/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , Suínos , Doenças dos Suínos/patologia , Receptores Toll-Like/genética , Desmame , Proteína da Zônula de Oclusão-1/genética , Proteína da Zônula de Oclusão-1/metabolismo
14.
J Anim Physiol Anim Nutr (Berl) ; 103(4): 1081-1089, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31008545

RESUMO

This study was conducted to investigate the effects of dietary supplementation with montmorillonite (MMT) on performance, intestinal endotoxin concentration, gut mucosal oxidation status, intestinal morphology and permeability, and immunological barrier function of laying hens during late production. Four hundred and eighty 75-week-old laying hens (Lohmann Brown) were randomly assigned to five treatments with eight replicates per treatment and 12 hens in each replicate. The hens were fed the basal diet supplemented with 0 (control), 0.3, 0.6, 0.9, or 1.2 g MMT/kg for 70 days. Compared with the control, supplemented with 0.9 g MMT/kg increased egg mass significantly (p < 0.05) during weeks 1-5 of the experiment. Supplemented with 0.6 and 0.9 g MMT/kg also increased the endotoxin concentration in the ileal digesta (p < 0.05), but decreased the MDA concentration in the ileum significantly (p < 0.05). The T-AOC in the jejunum of the group fed 0.3 g MMT/kg was significantly increased (p < 0.05). Compared with the control, the villus height:crypt depth of ileum from the groups fed 0.6, 0.9, and 1.2 g MMT/kg increased significantly (p < 0.05). The sIgA concentration of jejunum in the groups fed 0.6 and 0.9 g MMT/kg was higher (p < 0.05) than the control. The MMT supplementation linearly increased (p < 0.05) the mRNA expression of claudin-1 and claudin-5 in the jejunum. Dietary MMT supplementation down-regulated the mRNA expression of NF-κB P65 and TNF-α in the jejunum in a linear and quadratic manner (p < 0.05). The IL-1ß mRNA expression of jejunum in the group fed 0.6 g MMT/kg was lower (p < 0.05) than the control. In conclusion, dietary supplementation with MMT may improve the gut barrier functions and suggests that 0.9 g/kg of MMT in diets may be the optimal supplemental level for laying hens in late production.


Assuntos
Bentonita/farmacologia , Galinhas/fisiologia , Mucosa Intestinal/efeitos dos fármacos , Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Animais , Dieta/veterinária , Suplementos Nutricionais , Endotoxinas/química , Feminino , Conteúdo Gastrointestinal/química , Íleo/efeitos dos fármacos , Íleo/fisiologia , Mucosa Intestinal/fisiologia , Jejuno/efeitos dos fármacos , Jejuno/fisiologia
15.
Nat Commun ; 10(1): 1827, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015444

RESUMO

The Tip60/p400 chromatin-modifying complex, which is involved in the incorporation and post-translational modification of the H2A.Z histone variant, regulates cell proliferation and important signaling pathways, such as Wnt. Here, we study the involvement of H2A.Z in intestinal epithelial homeostasis, which is dependent on the finely-tuned equilibrium between stem cells renewal and differentiation, under the control of such pathway. We use cell models and inducible knock-out mice to study the impact of H2A.Z depletion on intestinal homeostasis. We show that H2A.Z is essential for the proliferation of human cancer and normal intestinal crypt cells and negatively controls the expression of a subset of differentiation markers, in cultured cells and mice. H2A.Z impairs the recruitment of the intestine-specific transcription factor CDX2 to chromatin, is itself a target of the Wnt pathway and thus, acts as an integrator for Wnt signaling in the control of intestinal epithelial cell fate and homeostasis.


Assuntos
Histonas/metabolismo , Homeostase/genética , Mucosa Intestinal/fisiologia , Via de Sinalização Wnt/genética , Animais , Fator de Transcrição CDX2/genética , Fator de Transcrição CDX2/metabolismo , Células CACO-2 , Diferenciação Celular/genética , Proliferação de Células/genética , Cromatina/genética , Células Epiteliais/fisiologia , Regulação da Expressão Gênica/fisiologia , Células HCT116 , Histonas/genética , Humanos , Mucosa Intestinal/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo
16.
Animal ; 13(10): 2199-2206, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30944048

RESUMO

Force-feeding was considered as a traditional high-efficiency approach to improve growth performance and accelerate fat deposition of Pekin ducks. However, force-feeding is a serious violation of international advocacy on animal welfare, because it can induce serious injuries to animals, such as damages to the digestive tract, effects on immunity and even severe oxidative stress. Therefore, it is urgent to stop force-feeding. The aim of this study was to determine the effects of force feeding on immune function, digestive function and oxidative stress in the mucosa of duodenum and jejunum of Pekin ducks. A total of 500 ducks were randomly divided into two groups. The control group was allowed to feed freely on a basal diet. The experimental group was force-fed by inserting a plastic feeding tube 8 to 10 inches long down the esophagus for 6 days. Compared with the control group, there was a significant (P<0.05) increase in serum diamine oxidase, d-lactic acid, endotoxin and corticosterone levels in the force-feeding group. The crypt depth in duodenum and jejunum showed significant differences (P<0.05) between the two groups and the intestinal villus epithelium cell was severely damaged in force-feeding group. Similarly, the activities of digestive enzymes as well as the levels of immune function in the duodenal and jejunal mucosa in the force-feeding group were significantly higher than the control group (P<0.05). However, there was a significant decrease in the superoxide dismutase, glutathione peroxidase and catalase levels with a marked increase in malondialdehyde level in duodenal and jejunal mucosa (P<0.05). In summary, at the end of the fattening period with force-feeding for 6 days, Pekin ducks experienced an adverse effect on the integrity of their duodenal and jejunal mucosa epithelium cell as well as their immune function and antioxidant capacity of Pekin ducks but also had improvement in digestive enzyme activities.


Assuntos
Ração Animal/análise , Patos/fisiologia , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Dieta/veterinária , Digestão , Patos/imunologia , Duodeno/imunologia , Duodeno/fisiologia , Nutrição Enteral/veterinária , Feminino , Glutationa Peroxidase/metabolismo , Mucosa Intestinal/imunologia , Mucosa Intestinal/fisiologia , Jejuno/imunologia , Jejuno/fisiologia , Malondialdeído/metabolismo , Estresse Oxidativo , Distribuição Aleatória , Superóxido Dismutase/metabolismo
17.
Biofabrication ; 11(3): 035023, 2019 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-30943455

RESUMO

A novel strategy of cryogenic 3D bioprinting assisted by free-from extrusion printing has been developed and applied to printing of a decellularized small intestinal submucosa (dSIS) slurry. The rheological properties, including kinetic viscosity, storage modulus (G'), and loss modulus (G″), were appropriate for free-from extrusion printing of dSIS slurry. Three different groups of scaffolds, including P500, P600, and P700, with filament distances of 500, 600, and 700 µm, respectively were fabricated at a 5 mm s-1 working velocity of the platform (V xy) and 25 kPa air pressure of the dispensing system (P) at -20 °C. The fabricated scaffolds were crosslinked via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) which resulted in a polyporous microstructure. The variations in the filament diameter and pore size were evaluated in the initial frozen state after printing, the lyophilized state, and after immersion in a PBS solution. The Young's modulus of the P500, P600, and P700 scaffolds was measured in wet and dry states for EDC-crosslinked scaffolds. The cell experiment results showed improved cell adhesion, viability, and proliferation both on the surface and within the scaffold, indicating the biocompatibility and suitability of the scaffold for 3D cell models. Further, gene and protein expression of normal skin fibroblasts on dSIS scaffolds demonstrated their ability to promote the production of some extracellular matrix proteins (i.e. collagen I, collagen III, and fibronectin) in vitro. Overall, this study presents a new potential strategy, by combining cryogenic 3D bioprinting with decellularized extracellular matrix materials, to manufacture ideal scaffolds for skin tissue engineering applications.


Assuntos
Bioimpressão/métodos , Mucosa Intestinal/fisiologia , Intestino Delgado/fisiologia , Pele/metabolismo , Engenharia Tecidual/métodos , Animais , Materiais Biocompatíveis/farmacologia , Proliferação de Células/efeitos dos fármacos , Reagentes para Ligações Cruzadas/química , Módulo de Elasticidade , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Ratos Sprague-Dawley , Reologia , Pele/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de Fourier , Sus scrofa , Tecidos Suporte/química
18.
Curr Obes Rep ; 8(2): 165-174, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30847735

RESUMO

PURPOSE OF REVIEW: Obesity is a state of chronic inflammation. This review aims to summarize recent data supporting the role of the intestinal mucosal barrier and the microbiome in causing adipose tissue inflammation as well as metabolic factors that can affect the intestinal barrier. RECENT FINDINGS: Obesity and its metabolic consequences, such as diabetes mellitus, are associated with disruption of the intestinal barrier function. Intestinal microbiota and diet play a key role in the maintenance of a healthy intestinal epithelium. Intestinal barrier dysfunction can lead to heightened inflammation, which in turn can further damage the intestinal barrier through the disruption of tight junction proteins. Intestinal barrier breakdown is associated with adipose tissue inflammation in different disease states, such as obesity, diabetes mellitus, HIV, and inflammatory bowel disease. Future therapeutic strategies to ameliorate intestinal barrier function may help reduce inflammation in obesity and other chronic conditions of increased intestinal permeability.


Assuntos
Tecido Adiposo/imunologia , Trato Gastrointestinal/imunologia , Inflamação , Obesidade/imunologia , Animais , Diabetes Mellitus , Dieta , Doença , Microbioma Gastrointestinal , Trato Gastrointestinal/patologia , HIV , Humanos , Mucosa Intestinal/fisiologia , Obesidade/metabolismo , Obesidade/terapia , Permeabilidade , Proteínas de Junções Íntimas
19.
Nat Commun ; 10(1): 1050, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30837466

RESUMO

A decline in protein homeostasis (proteostasis) has been proposed as a hallmark of aging. Somatic stem cells (SCs) uniquely maintain their proteostatic capacity through mechanisms that remain incompletely understood. Here, we describe and characterize a 'proteostatic checkpoint' in Drosophila intestinal SCs (ISCs). Following a breakdown of proteostasis, ISCs coordinate cell cycle arrest with protein aggregate clearance by Atg8-mediated activation of the Nrf2-like transcription factor cap-n-collar C (CncC). CncC induces the cell cycle inhibitor Dacapo and proteolytic genes. The capacity to engage this checkpoint is lost in ISCs from aging flies, and we show that it can be restored by treating flies with an Nrf2 activator, or by over-expression of CncC or Atg8a. This limits age-related intestinal barrier dysfunction and can result in lifespan extension. Our findings identify a new mechanism by which somatic SCs preserve proteostasis, and highlight potential intervention strategies to maintain regenerative homeostasis.


Assuntos
Envelhecimento/fisiologia , Proteínas de Drosophila/metabolismo , Mucosa Intestinal/fisiologia , Proteostase/fisiologia , Proteínas Repressoras/metabolismo , Células-Tronco/fisiologia , Animais , Animais Geneticamente Modificados , Pontos de Checagem do Ciclo Celular/fisiologia , Drosophila melanogaster , Células Epiteliais/fisiologia , Epitélio/fisiologia , Feminino , Mucosa Intestinal/citologia , Longevidade , Proteínas Nucleares/metabolismo
20.
Int J Mol Sci ; 20(5)2019 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-30857243

RESUMO

Abstract: The epithelial intermediate-conductance calcium/calmodulin-regulated KCa3.1 channel is considered to be a regulator of intestine function by controlling chloride secretion and water/salt balance. Yet, little is known about the functional importance of KCa3.1 in the intestinal epithelium in vivo. Our objective was to determine the impact of epithelial-specific inducible overexpression of a KCa3.1 transgene (KCa3.1+) and of inducible suppression (KCa3.1-) on intestinal homeostasis and function in mice. KCa3.1 overexpression in the duodenal epithelium of doxycycline (DOX)-treated KCa3.1+ mice was 40-fold above the control levels. Overexpression caused an inflated duodenum and doubling of the chyme content. Histology showed conserved architecture of crypts, villi, and smooth muscle. Unaltered proliferating cell nuclear antigen (PCNA) immune reactivity and reduced amounts of terminal deoxynucleotide transferase mediated X-dUTP nick end labeling (TUNEL)-positive apoptotic cells in villi indicated lower epithelial turnover. Myography showed a reduction in the frequency of spontaneous propulsive muscle contractions with no change in amplitude. The amount of stool in the colon was increased and the frequency of colonic contractions was reduced in KCa3.1+ animals. Senicapoc treatment prevented the phenotype. Suppression of KCa3.1 in DOX-treated KCa3.1- mice caused no overt intestinal phenotype. In conclusion, inducible KCa3.1 overexpression alters intestinal functions by increasing the chyme content and reducing spontaneous contractions and epithelial apoptosis. Induction of epithelial KCa3.1 can play a mechanistic role in the process of adaptation of the intestine.


Assuntos
Duodeno/fisiologia , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/metabolismo , Mucosa Intestinal/fisiologia , Animais , Digestão , Duodeno/ultraestrutura , Deleção de Genes , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/genética , Mucosa Intestinal/ultraestrutura , Camundongos , Camundongos Endogâmicos C57BL , Contração Muscular , Transgenes , Regulação para Cima
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