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1.
Inflamm Bowel Dis ; 29(2): 334-336, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36610699

RESUMO

The advent of single-cell technologies has revolutionized analyses of IBD-specific processes by identifying important, often novel, mucosal cells subpopulations and their associated functions. We discuss recent findings reporting transcriptomic and cellular diversity of treatment-naïve and treated patients with ileal-specific CD.


Assuntos
Doença de Crohn , Humanos , Doença de Crohn/genética , Transcriptoma , Íleo , Células Epiteliais , Membrana Mucosa
3.
BMC Endocr Disord ; 23(1): 9, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36624417

RESUMO

BACKGROUND: Studies on chemerin/chemokine-like receptor-1 have mainly focused on adipose and liver with the intestinal tissues largely overlooked. In this study conducted on obese mice, we have explored: 1) CMKLR1 expression in the ileums; 2) CMKLR1 inhibitor α-NETA on body weight and intestinal mucosa integrity hence the impact on hepatic steatosis and pathway involved. METHODS: Nineteen male C57BL/6 mice were randomly divided into five groups: normal diet group (ND), high-fat diet group (HFD), HFD + α-NETA group (NETA), HFD + PD98059 group (PD) and HFD + α-NETA + PD98059 group (NETA + PD). Mice were fed either with a chow diet or HFD for 12 weeks. At 12th week, mice of ND were put on the diet as before; mice of NETA received daily treatments of α-NETA (30 mg/kg) via gavage; mice of PD received daily treatment of PD98059 via tail vein injection; mice of NETA + PD received daily treatment of α-NETA + PD98059, all for another 4 weeks. At the time intervention ended, mice were sacrificed. The body weight, the liver pathologies were assessed. Ileal CMKLR1 mRNA was evaluated by rtPCR; ZO-1, ERK1/2 protein expression of ileal tissues by western blotting; liver TNF-α and serum endotoxin by Elisa. RESULTS: More weight gains in mice of HFD than ND (37.90 ± 3.00 g) vs (24.47 ± 0.50 g), P = 0.002; α-NETA reduced the body weight (33.22 ± 1.90 g) vs (37.90 ± 3.00 g), P = 0.033; and further reduced by NETA + PD98059: (31.20 ± 1.74 g) vs (37.30 ± 4.05 g), P = 0.032. CMKLR1 mRNA expression was up-regulated in ileum in group HFD compared with ND and down-regulated by α-NETA. Steatosis was only alleviated in group PD + NETA with less weight gain. No impact of α-NETA on ileal ZO-1 or pERK with western blotting, and no endotoxin level changes were detected. TNF-α was higher in group HFD than in group ND, while no significant difference between other groups. CONCLUSIONS: CMKLR1 mRNA was up-regulated in the ileum of obese mice and down-regulated by α-NETA along with a body weight control collaborating with ERK inhibitor PD98059. Steatosis was alleviated in a weight dependent way. α-NETA has no influence on intestinal mucosal integrity and no impact on steatohepatitis progression.


Assuntos
Fígado Gorduroso , Fator de Necrose Tumoral alfa , Masculino , Animais , Camundongos , Camundongos Obesos , Camundongos Endogâmicos C57BL , Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/etiologia , Fígado Gorduroso/prevenção & controle , Fígado , Aumento de Peso , Dieta Hiperlipídica/efeitos adversos , Mucosa Intestinal , Íleo , Peso Corporal , Receptores de Quimiocinas
4.
World J Gastroenterol ; 29(2): 332-342, 2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36687126

RESUMO

Magnesium (Mg2+) has an important role in numerous biological functions, and Mg2+ deficiency is associated with several diseases. Therefore, adequate intestinal absorption of Mg2+ is vital for health. The small intestine was previously thought to absorb digested Mg2+ exclusively through an unregulated paracellular mechanism, which is responsible for approximately 90% of total Mg2+ absorption. Recent studies, however, have revealed that the duodenum, jejunum, and ileum absorb Mg2+ through both transcellular and paracellular routes. Several regulatory factors of small intestinal Mg2+ uptake also have been explored, e.g., parathyroid hormone, fibroblast growth factor-23, apical acidity, proton pump inhibitor, and pH-sensing channel and receptors. The mechanistic factors underlying proton pump inhibitor suppression of small intestinal Mg2+, such as magnesiotropic protein dysfunction, higher mucosal bicarbonate secretion, Paneth cell dysfunction, and intestinal inflammation, are currently being explored. The potential role of small intestinal microbiomes in Mg2+ absorption has also been proposed. In this article, we reviewed the current knowledge on the mechanisms and regulatory factors of small intestinal Mg2+ absorption.


Assuntos
Magnésio , Inibidores da Bomba de Prótons , Humanos , Magnésio/metabolismo , Inibidores da Bomba de Prótons/uso terapêutico , Intestino Delgado/metabolismo , Íleo/metabolismo , Absorção Intestinal/fisiologia , Mucosa Intestinal/metabolismo
5.
BMC Microbiol ; 23(1): 18, 2023 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-36658475

RESUMO

BACKGROUND: The absorption and utilization of proteins by animals is affected by the amino acid (AA) release characteristics of their diets. In the present study, we aimed to determine the effects of diets with various amino acid release characteristics on the intestinal barrier function and diversity of gut microbiota of weaned pigs. RESULTS: Forty-eight pigs (7.45 ± 0.58 kg) were fed with diets having different amino acid release characteristics during a period of 28 days. We used a 2 × 3 full-factor (two protein levels and three protein sources with differing amino acid release characteristics) experimental design, with normal (standard terminal ileal digestibility of 17.5%) or low (standard terminal ileal digestibility of 14.9%) protein levels as the first factor. Casein (CAS), corn gluten meal (CGM) and a MIX diet were used as protein sources. Due to the more balanced release of amino acids, the diamine oxidase (DAO) concentrations in the CAS and MIX groups were significantly lower than those in the CGM group (P < 0.05); Reducing the dietary protein content from 17.5% to 14.9% had no significant effects on the levels of serum DAO or D-lactic acid. By contrast, it increased the microbial diversity (chao1 and ACE values) and the number of Lactobacillus in the jejunum (P < 0.05). The CAS-containing diet and the MIX diet resulted in significantly higher microbial diversity (Simpson and Shannon) than the CGM-containing diet in the jejunum. CONCLUSION: The balanced release of amino acids in CAS and MIX diets maintained intestinal barrier function and increased gut microbiota diversity. These findings could potentially provide a scientific reference for the rational preparation of piglet feed.


Assuntos
Digestão , Microbioma Gastrointestinal , Animais , Suínos , Aminoácidos/metabolismo , Dieta/veterinária , Íleo , Caseínas/metabolismo , Ração Animal/análise , Zea mays/metabolismo
6.
BMC Urol ; 23(1): 7, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36611146

RESUMO

PURPOSE: Repair of long-segment ureteral defect (LSUD) is challenging. Currently available procedures carry some potential complications. We modified the ileal graft by tapering the wall and stripping the mucosa to combat associated pitfalls and first reported the medium-term outcomes of 4 patients. MATERIAL AND METHODS: From September 2019 to October 2020, tapered demucosalized ileum (TDI) was used for LSUD reconstruction in 4 patients on the right (2 males and 2 females). Two patients were with panureteral avulsion and 2 with high-risk urothelial carcinoma in the distal ureter. TDI was made by tapering 1/2-2/3 of the antimesenteric ileal wall and stripping the mucosa with a blunt/blunt operating scissor. Follow-up modalities included serum creatinine, electrolytes, ultrasonography, CT urogram, renal scintigraphy, and ureteroscopy. RESULTS: Mean operation time was 443 min (range 360-550) and blood loss was negligible. The mean follow-up period was 29 months (range 23-36). Vesicoureteral reflux and related pyelonephritis occurred in 1 patient, necessitating a repair operation (Clavien-Dindo grade IIIb). No strictures, obstructions, metabolic disorders, or electrolyte imbalances were observed in the remaining patients. In carcinoma patients, ureteroscopy in month 18 post-operation revealed ileal mucosal regrowth in the form of dwarf isolated islands. All renal units maintained adequate drainage and function during the follow-up. CONCLUSIONS: Ileal wall tapering and mucosa stripping confined to the muscularis mucosae level will not result in shrinkage, fibrosis, or stricture formation of the ileal ureter. The present work provides evidence for further application of TDI in the replacement of LSUD in patients.


Assuntos
Carcinoma de Células de Transição , Ureter , Obstrução Ureteral , Neoplasias da Bexiga Urinária , Masculino , Feminino , Humanos , Ureter/diagnóstico por imagem , Ureter/cirurgia , Procedimentos Cirúrgicos Urológicos/métodos , Íleo/transplante , Constrição Patológica/cirurgia , Obstrução Ureteral/cirurgia
7.
J Ethnopharmacol ; 305: 116115, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-36587881

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Berberis lycium Royle, a member of the Berberidaceae family, is a high-value medicinal plant with a documented history of usage in traditional medicine and has demonstrated significant therapeutic results among local populations throughout the globe. It is used traditionally in many parts of Pakistan to treat diarrhea, abdominal spasms, coughs, and chest problems. AIM OF THE STUDY: To investigate the antispasmodic, bronchodilator, and antidiarrheal effects of B. lycium and its possible underlying mechanisms through in silico, in vitro, and in vivo studies. MATERIALS AND METHODS: LC ESI-MS/MS analysis was used to identify bioactive components within the hydromethanolic extract of B. lycium. In silico studies, including network pharmacology and molecular docking, were utilized to investigate the antispasmodic and bronchodilator properties of the extract's bioactive components. In vitro pharmacological studies were conducted using isolated rabbit jejunum, trachea, urinary bladder, and rat ileum preparations. In vivo antidiarrheal activities were conducted in mice, including castor oil-induced diarrhea, intestinal transit, and castor oil-induced enteropooling. RESULTS: The LC ESI-MS/MS analysis of the hydromethanolic extract of B. lycium identified 38 bioactive compounds. Network pharmacology study demonstrated that the mechanism of BLR for the treatment of diarrhea might involve IL1B, TLR4, PIK3R1, TNF, PTPRC, IL2, PIK3CD, and ABCB1, whereas, for respiratory ailments, it may involve PIK3CG, TRPV1, STAT3, ICAM1, ACE, PTGER2, PTGS2, TNF, MMP9, NOS2, IL2, CCR5, HRH1, and VDR. Molecular docking research revealed that chlorogenic acid, epigallocatechin, isorhamnetin, quinic acid, gallic acid, camptothecin, formononetin-7-O-glucoside, velutin, caffeic acid, and (S)-luteanine exhibited a higher docking score than dicyclomine with validated proteins of smooth muscle contractions such as CACB2_HUMAN, ACM3_HUMAN, MYLK_HUMAN, and PLCG1_HUMAN. In vitro investigations demonstrated that Blr.Cr, Blr.EtOAc, and Blr.Aq relaxed spontaneously contracting jejunum preparations; carbachol (1 µM)-induced and K+ (80 mM)-induced jejunum, trachea, and urinary bladder contractions in a concentration-dependent manner, similar to dicyclomine. Moreover, Blr.Cr, Blr.EtOAc, and Blr.Aq exhibited a rightward shift in Ca+2 and carbachol cumulative response curves, similar to dicyclomine, demonstrating the coexistence of antimuscarinic and Ca+2 antagonistic mechanisms due to the presence of alkaloids and flavonoids. In vivo antidiarrheal activities showed that the hydromethanolic extract was significantly effective against castor oil-induced diarrhea and castor oil-induced enteropooling, similar to loperamide, and charcoal meal intestinal transit, similar to atropine, in mice at doses of 50, 100, and 200 mg/kg body weight, which supports its traditional use in diarrhea. CONCLUSION: The dual blocking mechanism of muscarinic receptors and Ca+2 channels behind the smooth muscle relaxing activity reveals the therapeutic relevance of B. lycium in diarrhea, abdominal spasms, coughs, and chest problems.


Assuntos
Berberis , Lycium , Ratos , Humanos , Camundongos , Animais , Coelhos , Antidiarreicos/farmacologia , Antidiarreicos/uso terapêutico , Parassimpatolíticos/farmacologia , Parassimpatolíticos/uso terapêutico , Broncodilatadores/farmacologia , Óleo de Rícino , Diciclomina/efeitos adversos , Carbacol/farmacologia , Tosse/induzido quimicamente , Tosse/tratamento farmacológico , Interleucina-2/efeitos adversos , Simulação de Acoplamento Molecular , Espectrometria de Massas em Tandem , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Íleo , Ratos Sprague-Dawley , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Diarreia/metabolismo , Espasmo
9.
Dis Colon Rectum ; 66(1): e4-e9, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36515520

RESUMO

BACKGROUND: Anastomotic recurrence after bowel resection is problematic in patients with Crohn's disease. Antimesenteric functional end-to-end handsewn (Kono-S) anastomosis is associated with a low risk of anastomotic recurrence in patients with Crohn's disease. IMPACT OF INNOVATION: Kono-S anastomosis is effective but may be time-consuming. This study aimed to describe stapled antimesenteric functional end-to-end anastomosis for patients with Crohn's disease. TECHNOLOGY MATERIALS AND METHODS: The mesentery of the affected bowel segment was divided. A 5-cm-wide stapled functional end-to-end anastomosis was performed approximately 6 cm from the affected segment. The bowel was divided transversely exactly 90° to the intestinal lumen and the mesentery, and a supporting column was then constructed. PRELIMINARY RESULTS: From January 2018 to June 2021, 17 stapled antimesenteric functional end-to-end anastomoses were performed. The mean operative time was 106 (range, 80-135) minutes, and the time to construct the stapled antimesenteric functional end-to-end anastomosis was 21 (range, 18-28) minutes. The mean follow-up time was 8.9 (range, 1-15) months. In total, 10 patients underwent surveillance endoscopy. The average Rutgeerts score was 0.8 (range, 0-4), and the incidence of endoscopic recurrence was 11.8%. No postoperative mortality or anastomotic leakage was observed. CONCLUSION: Stapled antimesenteric functional end-to-end anastomosis may be a safe and time-saving procedure for patients with Crohn's disease. FUTURE DIRECTIONS: Further prospective studies with a large sample size are warranted.


Assuntos
Doença de Crohn , Procedimentos Cirúrgicos do Sistema Digestório , Humanos , Doença de Crohn/cirurgia , Estudos Prospectivos , Anastomose Cirúrgica/métodos , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Intestinos/cirurgia , Íleo/cirurgia
10.
J Anim Sci ; 1012023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36516453

RESUMO

In the current study, we hypothesized that an increase in dietary ileal indigestible protein concentration induces an increase in hindgut nitrogen utilization and nitrogen excretion and a shift in fecal microbiota in growing pigs, when compared to pigs given a high total protein diet. Three diets were prepared: 1) standard protein diet based on corn and soybean meal, 2) high-indigestible protein diet in which autoclaved, low-digestible soybean meal replaced soybean meal in the first diet, and 3) high protein diet where the inclusion rate of soybean meal was greater than that of the other diets. The 3 diets were fed to 18 barrows that were fitted with T-cannula at the ileo-cecal junction (initial body weight = 63.4 ±â€…8.0 kg) in a randomized complete block design with body weight as a blocking factor. Pigs were individually housed in pens and the experiment lasted for 23 d. On days 7 and 21, fecal samples were collected by rectal massage for microbiota analysis. Grab samples of feces were collected on days 20 and 21, and ileal digesta were collected on days 22 and 23 for the determination of energy and nitrogen utilization. Lower apparent ileal digestibility of nitrogen in the high-indigestible protein diet containing autoclaved soybean meal resulted in greater ileal indigestible nitrogen concentration (P < 0.05). Apparent total tract digestibility of nitrogen was lower (P < 0.05), and correspondingly nitrogen concentration and daily fecal nitrogen output were greater (P < 0.05) in the high-indigestible protein diet compared with the other diets. Apparent post-ileal digestibility and hindgut disappearance of nitrogen and gross energy were the greatest (P < 0.05) in the high protein diet, whereas a statistical difference was not observed in those variables between the standard protein diet and the high-indigestible protein diet. Beta diversity metrics of feces in the high-indigestible protein diet on day 21 were different (q < 0.05) from those in the other two diets, which indicates a shift in microbial communities. According to the results of the DESeq2, the direction of microbiota shift induced by the high-indigestible protein diet may have reduced fiber utilization in the hindgut. In conclusion, an increase in dietary ileal indigestible protein concentration increased fecal nitrogen excretion and shifted fecal microbial communities but did not increase nitrogen utilization in the hindgut.


Dietary protein concentration has been gradually reduced because reductions in protein concentration in swine diets are known to be beneficial in terms of feed costs, nitrogen excretion, and intestinal microbiota. However, ileal indigestible protein concentration may be more influential in those variables of pigs compared with total protein concentration in diets because ileal indigestible protein considers both protein concentration and digestibility of diets. In the current study, three diets were prepared: 1) corn-soybean meal diet, 2) high-indigestible protein diet replacing soybean meal in the first diet with autoclaved soybean meal, and 3) high protein diet where the inclusion rate of soybean meal was greater than that of the other diets. The experimental diets were fed to cannulated pigs and ileal digesta and fecal samples were collected. Fecal nitrogen output was greater in pigs fed the high-indigestible protein diet. Fecal microbiota was shifted by the high-indigestible protein diet, and this shift may not be beneficial. In conclusion, the impact of changes in ileal indigestible protein on fecal nitrogen excretion and fecal microbiota may be greater compared to changes in total protein concentration of diets in growing pigs.


Assuntos
Digestão , Nitrogênio , Suínos , Animais , Nitrogênio/metabolismo , Fezes , Dieta/veterinária , Íleo/metabolismo , Soja/metabolismo , Peso Corporal , Ração Animal/análise , Zea mays/metabolismo , Fenômenos Fisiológicos da Nutrição Animal
11.
Poult Sci ; 102(2): 102383, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36529100

RESUMO

This experiment evaluated the standard ileal digestibility (SID) of amino acids (AA) in 8 different sources of wheat fed to broilers and established prediction equations based on the chemical properties of wheat. A total of five hundred forty 1-day-old broilers were tested in 2 stages (from d 10 to 13 and from d 25 to 28). On d 13, 324 broilers were randomly assigned to 9 diets (6 replicate cages, 6 broilers per cage); on d 28, 216 broilers were randomly assigned to 9 diets (6 replicate cages, 4 broilers per cage). The 9 experimental diets included 8 test diets and 1 nitrogen-free diet. Titanium dioxide was added as an exogenous indicator at 0.5% of the diet. In 8 wheat samples, the mean values of total amino acids (TAA), dispensable amino acids (DAA), and indispensable amino acids (IAA) were 12.16% (CV 13.70%), 7.97% (CV 15.49%), and 4.20% (CV 11.47%). On d 13, the lowest SID of AA was Lys (86.71%), and the highest was Pro (97.98%). On d 28, the lowest SID of AA was His (81.31%), and the highest was Pro (96.83%). There was an effect of wheat source on the SID of AA except for Trp (P < 0.05); the broiler age had an effect on the SID of AA except for Tyr (P < 0.05); the SID of most AA were higher at d 13 compared to d 28. At d 13, the SID of AA was correlated with CP, NDF, and ST (P < 0.05). At d 28, the SID of AA was correlated with EE, Ash, ADF, and NDF (P < 0.05). The R2 value of stepwise regression equations to predict the SID of AA at d 13 was highest for Leu (R2 = 0.972), lowest for Asp (R2 = 0.785); at d 28 was highest for Gly (R2 = 0.995), lowest for His (R2 = 0.678). In conclusion, this experiment showed that the chemical properties of wheat can be used to establish accurate equations for predicting the SID of AA. This made it more efficient to obtain the SID of AA for wheat.


Assuntos
Aminoácidos , Triticum , Animais , Aminoácidos/metabolismo , Triticum/química , Galinhas/metabolismo , Antivirais/farmacologia , Digestão , Ração Animal/análise , Íleo/metabolismo , Fenômenos Fisiológicos da Nutrição Animal , Dieta/veterinária
12.
J Proteomics ; 270: 104739, 2023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36174954

RESUMO

This study evaluates how long-term dietary low ω6:ω3 ratio in sows and offspring's seaweed (SW) intake affects piglet intestinal function and growth through modifying ileum proteome. Sows were assigned to either control diet (CR, ω6:ω3 ratio = 13:1) or treatment diet (LR, ω6:ω3 = 4:1) during gestation and lactation (n = 8 each). The male weaned offspring were received a basal diet with or without SW powder supplementation (4 g/kg) for 21 days, denoted as SW and CT groups, respectively. In total, four groups of weaned piglets were formed following maternal and offspring's diets combination, represented by CRCT, CRSW, LRCT, and LRSW (n = 10 each). Piglet ileum tissue was collected on day 22 post-weaning and analysed using TMT-based quantitative proteomics. The differentially abundant proteins (n = 300) showed the influence of maternal LR diet on protein synthesis, cell proliferation, and cell cycle regulation. In contrast, the SW diet lowered the inflammation severity and promoted ileal tissue development in CRSW piglets but reduced the fat absorption capacity in LRSW piglets. These results uncovered the mechanism behind the anti-inflammation and intestinal-boosting effects of maternal LR diet in piglets supplemented with SW.


Assuntos
Proteoma , Alga Marinha , Suínos , Animais , Masculino , Feminino , Proteômica , Dieta , Suplementos Nutricionais , Lactação , Íleo , Verduras , Ração Animal/análise
13.
Clin Sci (Lond) ; 137(1): 109-127, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36503938

RESUMO

Menopausal women often face long-term estrogen treatment. G protein-coupled estrogen receptor (GPER) expressed in intestinal crypt was activated by estrogen therapy, but it was unclear whether chronic GPER activation during menopause had an effect on intestinal stem cells (ISCs). We tested the effect of chronic GPER activation on ISCs of ovariectomized (OVX) mice by injection of the selective GPER agonist G-1 for 28 days, or G-1 stimulation of organoids derived from crypts of OVX mice. G-1 up-regulated crypt depth, the number of Ki67+, bromodeoxyuridine+ cells and Olfm4+ ISCs, and the expression of ISCs marker genes (Lgr5, Olfm4 and Axin2). G-1 administration promoted organoid growth, increased the number of EdU+ cells per organoid and protein expression of Cyclin D1 and cyclin B1 in organoids. After G-1 treatment in vivo or in vitro, Paneth cell-derived Wnt3, Wnt3 effector ß-catenin and Wnt target genes c-Myc and Cyclin D1 increased in ileum or organoids. Once blocking the secretion of Wnt3 from Paneth cells, the effects of G-1 on organoids growth, ISCs marker genes and Wnt/ß-catenin signaling were abolished. G-1 did not affect the number of Paneth cells in ex vivo organoids, while activated Mmp7/cryptdin program in Paneth cells, promoted their maturation, and increased the expression of lysozyme protein. G-1 pretreatment in OVX mice inhibited radiation-induced ISCs proliferation injury and enhanced the resistance of mice to intestinal injury. In conclusion, chronic GPER activation prompted the Wnt3 synthesis in Paneth cells, thus increased the proliferation of ISCs via activation of Wnt3/ß-catenin signaling in OVX mice.


Assuntos
Ciclina D1 , Celulas de Paneth , Camundongos , Feminino , Animais , Celulas de Paneth/metabolismo , Ciclina D1/metabolismo , beta Catenina/metabolismo , Íleo/metabolismo , Células-Tronco , Via de Sinalização Wnt , Proliferação de Células , Estrogênios/farmacologia , Estrogênios/metabolismo , Mucosa Intestinal/metabolismo , Proteína Wnt3/metabolismo , Proteína Wnt3/farmacologia
14.
Int J Mol Sci ; 23(24)2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36555580

RESUMO

Voglibose is an α-glycosidase inhibitor that improves postprandial hyperglycemia and increases glucagon-like peptide-1 (GLP-1) secretion in patients with type 2 diabetes. Recently, there has been increasing interest in the anti-inflammatory effects of voglibose on the intestine, but the underlying mechanism is not clear. This study evaluated the effects and mechanisms of voglibose on glycemic control and intestinal inflammation. Type 2 diabetic KKAy mice were treated with voglibose (1 mg/kg) by oral gavage once daily. After 8 weeks, glucose metabolism, levels of short-chain fatty acids (SCFAs), systematic inflammatory factors, intestinal integrity and inflammation were evaluated using hematoxylin and eosin staining, immunohistochemistry, immunofluorescence and Western blot analysis. Voglibose ameliorated glucose metabolism by enhancing basal- and glucose-dependent GLP-1 secretion. Several beneficial SCFAs, such as acetic acid and propionic acid, were increased by voglibose in the fecal sample. Additionally, voglibose notably decreased the proportion of pro-inflammatory macrophages and the expression of nuclear factor kappa B but increased the expression of tight junction proteins in the ileum, thus markedly improving intestinal inflammatory damage and reducing the systematic inflammatory factors. Ileal genomics and protein validation suggested that voglibose attenuated inositol-requiring protein 1α-X-box binding protein 1-mediated endoplasmic reticulum stress (ERS). Together, these results showed that voglibose enhanced the secretion of GLP-1, which contributed to the glycemic control in KKAy mice at least in part by regulating intestinal inflammation and the expression of ERS factors.


Assuntos
Diabetes Mellitus Tipo 2 , Camundongos , Animais , Diabetes Mellitus Tipo 2/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Inositol/farmacologia , Íleo/metabolismo , Glucose
15.
BMC Vet Res ; 18(1): 447, 2022 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-36564755

RESUMO

BACKGROUND: Lysine (Lys) is the first limiting amino acid for pigs fed corn-soybean meal diets. Three experiments were conducted to estimate the optimal standardized ileal digestible (SID) Lys requirement for growing (Exp. 1), early finishing (Exp. 2), and late finishing (Exp. 3) pigs under commercial conditions. RESULTS AND CONCLUSIONS: In Exp. 1, a total of 650 growing pigs (32.21 ± 0.33 kg bodyweight), were allocated to 5 dietary treatments supplemented with 0.75, 0.85, 0.94, 1.03, and 1.13% SID Lys. Each treatment had 5 replicate pens with 26 pigs per pen. The lowest feed to gain ratio (F:G) was obtained by pigs fed the 1.03% Lys diet and F:G showed both a linear and a quadratic response with increasing Lys (P < 0.05). Based on broken-line and quadratic analysis models, dietary SID Lys levels for the minimum F:G were 0.94%. In Exp. 2, 650 finishing pigs (57.24 ± 2.00 kg bodyweight) were allotted to 5 dietary treatments providing SID Lys of 0.63, 0.71, 0.79, 0.87, and 0.95%. Each treatment had 5 replicates, 26 pigs per replication. The highest final bodyweight was achieved by 0.79% Lys while the highest average daily gain (ADG) and average daily feed intake (ADFI) was achieved by pigs consuming the 0.87% Lys diet (P < 0.05). Additionally, the lowest F:G was obtained by pigs fed the 0.79 and 0.87% Lys diet (P < 0.05). Based on broken-line and quadratic analysis models, the optimum Lys was 0.81 and 0.82% for ADG and F:G, respectively. In Exp. 3, 600 late finishing pigs (92.22 ± 2.41 kg bodyweight), were divided into 5 treatments providing Lys levels of 0.53, 0.60, 0.66, 0.73, and 0.79%. Each treatment had 5 replicates, 24 pigs per replication. Results showed that final bodyweight, ADG, ADFI, and F:G was not affected by increasing dietary Lys level, suggesting that the lowest SID Lys (0.53%) was sufficient for this group of pigs. Taken together, the SID Lys requirement for pigs from 30 to 60 kg, 60 to 90 kg, 90 to 120 kg was 0.94%, 0.81 to 0.82, and 0.53%, respectively, depending on the response criteria with performance maximized.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Lisina , Suínos , Animais , Lisina/metabolismo , Ração Animal/análise , Íleo/metabolismo , Dieta/veterinária , Peso Corporal
17.
Sci Transl Med ; 14(676): eabp9675, 2022 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-36542690

RESUMO

Acute graft-versus-host disease (aGVHD), which is driven by allogeneic T cells, has a high mortality rate and limited treatment options. Human ß-defensin 2 (hBD-2) is an endogenous epithelial cell-derived host-defense peptide. In addition to its antimicrobial effects, hBD-2 has immunomodulatory functions thought to be mediated by CCR2 and CCR6 in myeloid cells. In this study, we analyzed the effect of recombinant hBD-2 on aGVHD development. We found that intestinal ß-defensin expression was inadequately induced in response to inflammation in two independent cohorts of patients with aGVHD and in a murine aGVHD model. Treatment of mice with hBD-2 reduced GVHD severity and mortality and modulated the intestinal microbiota composition, resulting in reduced neutrophil infiltration in the ileum. Furthermore, hBD-2 treatment decreased proliferation and proinflammatory cytokine production by allogeneic T cells in vivo while preserving the beneficial graft-versus-leukemia effect. Using transcriptome and kinome profiling, we found that hBD-2 directly dampened primary murine and human allogeneic T cell proliferation, activation, and metabolism in a CCR2- and CCR6-independent manner by reducing proximal T cell receptor signaling. Furthermore, hBD-2 treatment diminished alloreactive T cell infiltration and the expression of genes involved in T cell receptor signaling in the ilea of mice with aGVHD. Together, we found that both human and murine aGVHD were characterized by a lack of intestinal ß-defensin induction and that recombinant hBD-2 represents a potential therapeutic strategy to counterbalance endogenous hBD-2 deficiency.


Assuntos
Doença Enxerto-Hospedeiro , beta-Defensinas , Humanos , Animais , Camundongos , beta-Defensinas/genética , beta-Defensinas/metabolismo , beta-Defensinas/farmacologia , Infiltração de Neutrófilos , Íleo , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/genética , Receptores de Antígenos de Linfócitos T
18.
Int J Mol Sci ; 23(24)2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36555421

RESUMO

To investigate developmental changes in immunity and different responses to weaning stress of piglets from different breeds during suckling and weaning periods, a total of 30 litters of Taoyuan black (TB) piglets, Xiangcun black (XB) piglets, and Duroc (DR) piglets (ten litters per breed) were selected at 1, 10, 21, and 24 days of age, respectively. The results showed that the liver index of TB piglets was higher at 10 days of age than that of the other days of age and breeds. Regardless of the days of age, TB and XB piglets had a higher plasma IgA level and lower ileal IgM level than in the DR piglets, and XB piglets had a lower plasma IgG level than the other breeds. TB and XB piglets had a higher IL-6 level and lower IL-17 level in plasma at 24 days of age than DR piglets, regardless of the days of age. The ileal levels of IL-2, IL-10, IFN-γ, and TNF-α were lower in the TB and XB piglets at 24 days of age than in the DR piglets. The ileal expression levels of IRAK1, CD14, MyD88, and NF-κB were down-regulated in the TB and XB piglets at 24 days of age compared to those in the DR piglets. These findings suggest that there were differences in the development of immune function among different pig breeds. Moreover, TB and XB piglets presented stronger resistance to weaning stress than the DR piglets, which may be related to the immune regulation mediated by the MyD88/NF-κB signaling pathway.


Assuntos
Imunidade , Desmame , Animais , Íleo/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Suínos
19.
Magy Seb ; 75(4): 261-264, 2022 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-36515914

RESUMO

Small intestinal transplantation has emerged as an essential treatment for intestinal failure, but its relatively high graft rejection rate and mortality rate when compared to those of other transplanted organs has led to difficulties in post-transplantation treatment management. The recently-developed technique of creating organoids from somatic stem cells has created a challenging opportunity to develop a treatment that involves the creation of a substitute small intestine using autologous cells instead of transplanting another individual's small intestines. The remaining partial large intestine is then used as a segmental graft, and autologous small intestinal organoid transplantation is conducted on its epithelium in order to create a pedunculated hybrid graft. This is a new surgical technique for interposing with the original ileocecal region. The hybrid large intestine acquires both the lymphatic vessels that are involved in nutrient absorption and the original peristaltic function of the large intestine.This lecture touches upon the history of the development of organoid medicine, after which an introduction is provided of the revolutionary surgical technique in which a functional small intestine is created by regenerating autologous cells.The content here was introduced in a special lecture (online) at the 29th Congress of the Experimental Surgical Session of the Hungarian Surgical Society (Host: Dr. Norbert Nemeth, 9/9/2022, Budapest).


Assuntos
Intestino Delgado , Organoides , Humanos , Intestino Delgado/cirurgia , Íleo , Regeneração , Mucosa Intestinal , Intestinos/transplante
20.
Int J Mol Sci ; 23(23)2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36499272

RESUMO

Spore formers are ubiquitous microorganisms commonly isolated from most environments, including the gastro-intestinal tract (GIT) of insects and animals. Spores ingested as food and water contaminants safely transit the stomach and reach the intestine, where some of them germinate and temporarily colonize that niche. In the lower part of the GIT, they re-sporulate and leave the body as spores, therefore passing through their entire life cycle in the animal body. In the intestine, both un-germinated spores and germination-derived cells interact with intestinal and immune cells and have health-beneficial effects, which include the production of useful compounds, protection against pathogenic microorganisms, contribution to the development of an efficient immune system and modulation of the gut microbial composition. We report a genomic and physiological characterization of SF106 and SF174, two aerobic spore former strains previously isolated from ileal biopsies of healthy human volunteers. SF106 and SF174 belong respectively to the B. subtilis and Alkalihalobacillus clausii (formerly Bacillus clausii) species, are unable to produce toxins or other metabolites with cytotoxic activity against cultured human cells, efficiently bind mucin and human epithelial cells in vitro and produce molecules with antimicrobial and antibiofilm activities.


Assuntos
Trato Gastrointestinal , Esporos Bacterianos , Animais , Humanos , Esporos Bacterianos/fisiologia , Intestinos , Íleo , Estômago , Bacillus subtilis/fisiologia
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