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1.
Methods Mol Biol ; 2559: 41-49, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36180625

RESUMO

Elucidation of the symbiotic relationship between the host and its gut microbiota is critically important for understanding host pathophysiology. Peripherally derived regulatory T cells (pTregs) are recognized as central to immune homeostasis in the intestine. Moreover, the gut microbiota nourishes the intestinal and systemic immune systems, including pTreg, via their metabolites and other components. Therefore, methods to detect pTreg as well as to analyze the interactions between the gut microbiota and pTreg are important for better understanding of the symbiotic relationship with these microorganisms. Here, we describe a protocol to isolate colonic lamina propria cells and analyze pTregs in mice.


Assuntos
Microbioma Gastrointestinal , Linfócitos T Reguladores , Animais , Colo , Mucosa Intestinal , Intestinos , Camundongos
2.
J Ethnopharmacol ; 300: 115690, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36075274

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Xianglian Pill (XLP) is a classical Chinese medicine prescription applied for controlling ulcerative colitis (UC). Whereas, the underlying mechanism remains unclear. AIM OF THE STUDY: The present work was aimed to investigate the mechanism of XLP in dextran sulfate sodium (DSS)-induced UC via the Toll Like Receptor 4 (TLR4)/Myeloid Differentiation factor 88 (MyD88)/Nuclear Factor kappa-B (NF-κB) signaling in mice. MATERIALS AND METHODS: The major components of XLP were detected by high-performance liquid chromatography-diode array detection (HPLC-DAD). The ulcerative colitis model was induced by DSS in mice. 5-Amino Salicylic Acid (5-ASA) group and XLP group were intragastrically treated. Disease activity index (DAI) and colon length were monitored and hematoxylin-eosin (HE) staining was conducted. Gasdermin D (GSDMD)-N and TLR4 expressions in colon tissues were visualized by immunofluorescence. TLR4 mRNA was measured by Real Time Quantitative PCR (RT-qPCR). The expressions of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), active-caspase-1, GSDMD-N, TLR4, MYD88, NF-κB, p-NF-κB, and the ubiquitination of TLR4 in colon tissues were detected by Western blot. Myeloperoxidase (MPO) enzyme activity was examined and serum inflammatory factors Interleukin (IL)-1ß, IL-6, Tumor Necrosis Factor-α (TNF-α), and IL-18 were determined by Enzyme-linked Immunosorbent Assay (ELISA). TLR4-/- mice were applied for verifying the mechanism of XLP attenuated DSS symptoms. RESULTS: The XLP treatment extended colon length, reduced DAI, and attenuated histopathological alteration in DSS-induced mice. XLP administration suppressed MPO activity and reduced the content of IL-1ß, IL-6, TNF-α and IL-18 in serum. XLP also inhibited the expression levels of GSDMD-N, TLR4, NLRP3, active-caspase-1, MyD88, p-NF-κB/NF-κB in colon tissues of DSS-induced mice. TLR4-/- mice proved that TLR4 was involved in XLP-mediated beneficial effect on DSS-induced ulcerative colitis. CONCLUSIONS: XLP might treat ulcerative colitis by regulating the TLR4/MyD88/NF-κB signaling pathway.


Assuntos
Colite Ulcerativa , Fator 88 de Diferenciação Mieloide , Animais , Caspases/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Amarelo de Eosina-(YS)/metabolismo , Amarelo de Eosina-(YS)/farmacologia , Amarelo de Eosina-(YS)/uso terapêutico , Hematoxilina/metabolismo , Hematoxilina/farmacologia , Hematoxilina/uso terapêutico , Interleucina-18/metabolismo , Interleucina-18/farmacologia , Interleucina-18/uso terapêutico , Interleucina-6/metabolismo , Camundongos , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Peroxidase/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
3.
J Ethnopharmacol ; 300: 115741, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36162543

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Pulsatilla decoction (PD), is an herbal formula commonly used for the treatment of ulcerative colitis (UC) in clinical practice, but the mechanism of PD alters the colitis remains elusive. AIM OF THE STUDY: To evaluate the intervention effect of PD on Dextran Sodium Sulfate (DSS)-induced UC based on gut microbiota and intestinal short-chain fatty acid (SCFAs) metabolism, and to investigate the mechanism of action of PD in treating UC. MATERIALS AND METHODS: A 3% (wt/vol) DSS-induced ulcerative colitis model in C57BL/6 male mice was used to evaluate the effect of oral PD in treating UC. The changes in gut microbiota in mice were analyzed by 16SrDNA gene sequencing, and the content of SCFAs in the intestinal contents of mice was determined by gas chromatography-mass spectrometry (GC-MS). Enzyme-linked immunosorbent assay (ELISA) was applied to analyze the expression of inflammatory cytokines in serum and colonic tissues, and western blotting (WB) was applied to analyze the expression of tight junction proteins in colonic tissues. RESULTS: PD can alleviate the symptoms of UC mice, Pulsatilla Decoction high dose treatment group (PDHT) shows the best effect. Compared with the DSS group, the PDHT had significantly lower body mass, disease activity index (DAI) score, colonic macroscopic damage index (CMDI) score, and pathological damage score, at the phylum level, the relative abundance of Bacteroidetes increased while that of Firmicutes and Proteobacteria decreased, at the Genus level, the abundance of Bacteroides and Lachnospiraceae.NK4A136.group increased while that of Clostridium. sensu.stricto。, Escherichia. shigella and Turicibacter decreased. Compared with the DSS group, acetate, propionate, and total SCFAs in the PDHT with significantly higher levels. The concentrations of interleukin-1ß (L-1ß), tumor necrosis factor-alpha (TNF-α), and interleukin-17 (IL-17) decreased whereby the concentration of interleukin-10 (IL-10) increased in the PDHT group. The expression levels of Occludin, zonula occludens-1 (ZO-1), Claudin1, Claudin5, G protein-coupled receptor43 (GPR43) protein, and the relative expression of ZO-1 and Occludin mRNA were significantly increased PDHT group. CONCLUSIONS: PD has a good therapeutic effect on UC mice. The pharmacological mechanism is probably maintaining the homeostasis and diversity of gut microbiota, increasing the content of SCFAs, and repairing the colonic mucosal barrier.


Assuntos
Colite Ulcerativa , Colite , Pulsatilla , Animais , Bactérias/metabolismo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colo , Citocinas/metabolismo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Ácidos Graxos Voláteis/metabolismo , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Interleucina-1beta/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ocludina/metabolismo , Propionatos , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
4.
Life Sci Alliance ; 6(1)2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36384894

RESUMO

The role of the alternate G protein-coupled estrogen receptor 1 (GPER1) in colorectal cancer (CRC) development and progression is unclear, not least because of conflicting clinical and experimental evidence for pro- and anti-tumorigenic activities. Here, we show that low concentrations of the estrogenic GPER1 ligands, 17ß-estradiol, bisphenol A, and diethylstilbestrol cause the generation of lagging chromosomes in normal colon and CRC cell lines, which manifest in whole chromosomal instability and aneuploidy. Mechanistically, (xeno)estrogens triggered centrosome amplification by inducing centriole overduplication that leads to transient multipolar mitotic spindles, chromosome alignment defects, and mitotic laggards. Remarkably, we could demonstrate a significant role of estrogen-activated GPER1 in centrosome amplification and increased karyotype variability. Indeed, both gene-specific knockdown and inhibition of GPER1 effectively restored normal centrosome numbers and karyotype stability in cells exposed to 17ß-estradiol, bisphenol A, or diethylstilbestrol. Thus, our results reveal a novel link between estrogen-activated GPER1 and the induction of key CRC-prone lesions, supporting a pivotal role of the alternate estrogen receptor in colon neoplastic transformation and tumor progression.


Assuntos
Centrossomo , Estrogênios , Receptores de Estrogênio , Receptores Acoplados a Proteínas G , Humanos , Centrossomo/metabolismo , Instabilidade Cromossômica/genética , Colo , Dietilestilbestrol/farmacologia , Estradiol/farmacologia , Estrogênios/farmacologia , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo
5.
Gastrointest Endosc Clin N Am ; 33(1): 83-97, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36375889

RESUMO

Multimodal assessment of colorectal polyps is needed before decision-making for endoscopic mucosal resection or endoscopic submucosal dissection (ESD). Assessment should include morphology according to Paris classification, magnification endoscopy for vascular pattern, and Kudo pit pattern analysis. ESD should be offered to patients that have Vi pit pattern, lateral spreading tumors (LST) granular multinodular and LST nongranular, lesions with fibrosis and those in patients with inflammatory bowel disease. A defined strategy for resection and planning is crucial for successful and efficient resection with a clear audit of outcomes aiming for a perforation and bleeding rate of less than 1% and R0 resection greater than 90%.


Assuntos
Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Humanos , Ressecção Endoscópica de Mucosa/métodos , Reto/patologia , Resultado do Tratamento , Colo , Endoscopia Gastrointestinal , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologia , Mucosa Intestinal/cirurgia , Mucosa Intestinal/patologia
6.
J Ethnopharmacol ; 301: 115765, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36195303

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Mesua Assamica (King & prain) Kosterm. (MA) is an evergreen endemic medicinal tree available in Assam in India and other parts of south Asia. The bark of the plant is traditionally used for ant-malarial activity and treating fevers. It was reported to have anti-oxidant, anti-inflammatory, anti-diabetic, anti-cancer and anti-malarial properties, but no research findings have been reported about its protective activity on intestinal inflammatory disorders like ulcerative colitis (UC) yet. AIM OF THE STUDY: The aim of the current study is to evaluate the anti-ulcerative property of ethanolic extract of MA (MAE) in-vitro on GloResponse™ NF-кB-RE-luc2P HEK 293 cells for its anti-oxidant and anti-inflammatory activities and in-vivo chronic restraint stress aggravated dextran sodium sulfate (DSS)-induced UC model. MATERIALS AND METHODS: The chemical constituents of MAE were identified by LC-MS/MS. The in-vitro effects of MAE on GloResponse™ NF-кB-RE-luc2P HEK 293 cells stimulated with TNF-α 30 ng/ml were investigated for its potential therapeutic effects. Parameters such as body weights, behavioural, colonoscopy, colon lengths and spleen weights were measured and recorded in chronic restraint stress aggravated DSS-induced UC model in C57BL/6 mice. Histological, cytokines and immunoblotting analysis in the colon tissues were determined to prove its anti-inflammatory and anti-oxidant activities. RESULTS: MAE poses significant anti-oxidant and anti-inflammatory activity in-vitro in GloResponse™ NF-кB-RE-luc2P HEK 293 cells evidenced by DCFDA and immunoflourescence assay. MAE treatment at 100 mg/kg and 200 mg/kg for 14 consecutive days has reduced Disease activity Index (DAI), splenomegaly and improved the shortened colon length and sucrose preference in mice. MAE treatment has increased the levels of anti-oxidants like GSH and reduced the levels of MDA, MPO and nitrite levels in colon tissues. Moreover, MAE has ameliorated neutrophil accumulation, mucosal and submucosal inflammation and crypt density evidenced by histopathology. Furthermore, MAE treatment significantly reduced the increased pro-inflammatory cytokines like IL-6, IL-1ß and TNF-α. we found from immunoblotting that there is a concomitant decrease in protein expression of NF-κB, STAT3 signalling cascades and phosphorylation of IKBα with an increase in Nrf2, SOD2, HO-1 and SIRT1 in colon tissues. In addition, we have performed molecular docking studies confirming that phytochemicals present in the MAE have a stronger binding ability and druggability to the NF-κB, Nrf2 and SIRT1 proteins. CONCLUSIONS: MAE exhibited significant anti-colitis activity on chronic restraint stress aggravated DSS-induced ulcerative colitis via regulating NF-κB/STAT3 and HO-1/Nrf2/SIRT1 signaling pathways.


Assuntos
Colite Ulcerativa , NF-kappa B , Animais , Humanos , Camundongos , Anti-Inflamatórios , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Cromatografia Líquida , Colite Ulcerativa/induzido quimicamente , Colo , Citocinas/metabolismo , Sulfato de Dextrana , Células HEK293 , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Casca de Planta/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/metabolismo , Transdução de Sinais , Sirtuína 1/metabolismo , Espectrometria de Massas em Tandem , Fator de Necrose Tumoral alfa/metabolismo
7.
Food Chem ; 398: 133801, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35961168

RESUMO

Effects of pectin, inulin, and their combination on the production of microbiota-derived indoles and short-chain fatty acids (SCFAs) from different colon segments were investigated in a batch system inoculated with microbiota from proximal colon (PC) and distal colon (DC) compartments of the Simulator of Human Intestinal Microbial Ecosystem. Bacteria from DC compartment had a higher abundance of Firmicutes and a stronger capacity to produce indoles and SCFAs than bacteria from PC compartment. Fiber supplementation significantly increased the production of SCFAs, indole-3-propionic acid, and indole-3-lactic acid, but decreased the production of oxindole, tryptamine, and serotonin. Pectin specifically promoted the production of indole-3-acetic acid and indole-3-aldehyde. Interestingly, supplementation of pectin or inulin increased the relative abundance of Bacteroidetes whereas supplementation of a mixture of two fibers decreased it. Overall, these results suggest that fiber supplementation and colon segment affect the composition of gut microbiota and the microbial catabolism of tryptophan.


Assuntos
Inulina , Microbiota , Bactérias/genética , Bactérias/metabolismo , Colo/metabolismo , Fibras na Dieta/metabolismo , Ácidos Graxos Voláteis/metabolismo , Fermentação , Humanos , Indóis/metabolismo , Inulina/metabolismo , Pectinas/metabolismo
8.
J Visc Surg ; 159(1): 21-30, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33349570

RESUMO

PURPOSE OF THE STUDY: To determine the statistical indicators aimed at identifying patients for whom ambulatory colectomy could be proposed without additional risk. PATIENTS AND METHODS: The medical charts of patients who benefited from scheduled colonic or rectal resection during conventional hospitalization stays between 2018 and 2019 were reviewed. Eligibility for ambulatory colectomy was defined by hospital stay≤4 days and absence of any postoperative complication. Patient characteristics were compared, and the results were modeled in the form of a decision-making tree. The effect of an enhanced recovery after surgery (ERAS) protocol for each sub-group was calculated. RESULTS: One hundred and ten (110) patients were selected (41 "eligible" and 69 "non-eligible"). Median age was 73 years (27-95). Nearly 80% of the patients were operated for cancer. In multivariate analysis, age (≥65 years, OR=3.15, CI95%=1.22-8.12), diabetes (OR=3.91, CI95%=1.03-14.8) and indication (sigmoidectomy for diverticulosis, OR=0.21, CI=95%=0.05-0.9) were the only identified independent variables. Likelihood for ambulatory eligibility was 83.3% (<65 years, sigmoidectomy pour diverticulosis, +ERAS=92%-96.9%), 58.3% (<65 years, other indication, +ERAS=63.4%-89.9%), 35.7% (≥65 years without diabetes, +ERAS=40.0%-55.9%) and 8.3% (≥65 years with diabetes, +ERAS=10.0%-20.1%). CONCLUSION: Sigmoidectomy for diverticulosis in a patient under 65 years age represents the best indication for ambulatory colectomy, a procedure that must not be proposed to diabetic patients over 65 years of age. In the other cases (<65 years operated in another indication and non-diabetic≥65 years), ambulatory surgery is possible, pending satisfactory application of the ERAS protocol.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Laparoscopia , Protectomia , Idoso , Colectomia/métodos , Colo/cirurgia , Humanos , Laparoscopia/métodos , Tempo de Internação , Complicações Pós-Operatórias/etiologia
9.
Eur J Histochem ; 66(1)2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35057584

RESUMO

G-protein-coupled receptor 41 (GPR41) and G-protein-coupled receptor 43 (GPR43) are important short-chain fatty acids (SCFAs) receptors. Previous studies indicated that GPR41 and GPR43 are involved in the secretion of gastrointestinal peptides, and glucose and lipid metabolism, and are closely related to obesity and type II diabetes, and other diseases. The purpose of the study was to explore the relationship between the GPR41 and GPR43 and seasonal breeding, and provide new prospects for further exploring the nutritional needs of breeding. We identified the localization and expression levels of GPR41 and GPR43 in the colon of the wild ground squirrels (Spermophilus dauricus) both in the breeding season and non-breeding season. The histological results revealed that the lumen diameter of the colon had obvious seasonal changes, and the diameter of the colonic lumen in the non-breeding season was larger than that in the breeding season. Immunohistochemical staining suggested GPR41 and GPR43 have expressed in the simple layer columnar epithelium. In addition, compared with the breeding season, the mRNA and protein expression levels of GPR41 and GPR43 in the colon were higher during the non-breeding season. In general, these results indicated GPR41 and GPR43 might play a certain role in regulating seasonal breeding.


Assuntos
Diabetes Mellitus Tipo 2 , Sciuridae , Animais , Colo , Ácidos Graxos Voláteis/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Sciuridae/metabolismo , Estações do Ano
10.
Sci Rep ; 12(1): 18551, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36329098

RESUMO

Digestion of dietary fibers by gut bacteria has been shown to stimulate intestinal mineral absorption [e.g., calcium (Ca2+) and magnesium (Mg2+)]. Although it has been suggested that local pH and short-chain fatty acid (SCFA) concentrations determine divalent cation absorption, the exact molecular mechanisms are still unknown. Therefore, this study aimed to determine the effects of SCFAs on intestinal Mg2+ absorption. We show that the butyrate concentration in the colon negatively correlates with serum Mg2+ levels in wildtype mice. Moreover, Na-butyrate significantly inhibited Mg2+ uptake in Caco-2 cells, while Ca2+ uptake was unaffected. Although Na-butyrate significantly lowered total ATP production rate, and resulted in increased phosphorylation of AMP-activated protein kinase (AMPK), inhibition of Mg2+ uptake by butyrate preceded these consequences. Importantly, electrophysiological examinations demonstrated that intracellular butyrate directly reduced the activity of the heteromeric Mg2+ channel complex, transient receptor potential melastatin (TRPM)6/7. Blocking cellular butyrate uptake prevented its inhibitory effect on Mg2+ uptake, demonstrating that butyrate acts intracellularly. Our work identified butyrate as novel regulator of intestinal Mg2+ uptake that works independently from metabolic regulation. This finding further highlights the role of microbial fermentation in the regulation of mineral absorption.


Assuntos
Butiratos , Magnésio , Humanos , Camundongos , Animais , Butiratos/farmacologia , Butiratos/metabolismo , Células CACO-2 , Magnésio/metabolismo , Colo/metabolismo , Ácidos Graxos Voláteis/metabolismo
11.
BMC Med Genomics ; 15(1): 229, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36320063

RESUMO

BACKGROUND: Colorectal cancer is common among obese individuals. The purpose of the current study was to determine changes in DNA methylation status and mRNA expression of thyroid hormone receptor beta (THRB), as a tumor suppressor, and thyroid hormone inactivating enzyme, type 3 deiodinase (DIO3) genes, in human epithelial colon tissues of healthy obese individuals. METHODS: Colon biopsies were analyzed by methylation sensitive-high resolution melting (MS-HRM) to investigate promoter methylation of DIO3 and THRB, and by quantitative real-time polymerase chain reaction to assay expression of DIO3 and THRB mRNA on eighteen obese and twenty-one normal-weight healthy men. RESULTS: There was no significant difference in mean methylation levels at the THRB promoter region between the two groups. Nevertheless, obesity decreased THRB expression levels, significantly (P < 0.05; fold change: 0.19). Furthermore, obesity attenuated DNA methylation (P < 0.001) and enhanced mRNA expression of DIO3 (P < 0.05; fold change: 3). CONCLUSIONS: Our findings suggest that obesity may alter expression of THRB and DIO3 genes through epigenetic mechanism. Alterations of THRB and DIO3 expressions may predispose colon epithelium of obese patients to neoplastic transformation.


Assuntos
Metilação de DNA , Receptores beta dos Hormônios Tireóideos , Masculino , Humanos , Receptores beta dos Hormônios Tireóideos/genética , Receptores beta dos Hormônios Tireóideos/metabolismo , RNA Mensageiro/genética , Hormônios Tireóideos/metabolismo , Obesidade/genética , Colo/metabolismo , Epitélio/metabolismo
12.
Nutrients ; 14(21)2022 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-36364715

RESUMO

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the digestive tract and is typically accompanied by characteristic symptoms, such as abdominal pain, diarrhea, and bloody stool, severely deteriorating the quality of the patient's life. Electrolyzed hydrogen water (EHW) has been shown to alleviate inflammation in several diseases, such as renal disease and polymyositis/dermatomyositis. To investigate whether and how daily EHW consumption alleviates abdominal pain, the most common symptom of IBD, we examined the antioxidative and anti-inflammatory effects of EHW in an IBD rat model, wherein colonic inflammation was induced by colorectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS). We found that EHW significantly alleviated TNBS-induced abdominal pain and tissue inflammation. Moreover, the production of proinflammatory cytokines in inflamed colon tissue was also decreased significantly. Meanwhile, the overproduction of reactive oxygen species (ROS), which is intricately involved in intestinal inflammation, was significantly suppressed by EHW. Additionally, expression of S100A9, an inflammatory biomarker of IBD, was significantly suppressed by EHW. These results suggest that the EHW prevented the overproduction of ROS due to its powerful free-radical scavenging ability and blocked the crosstalk between oxidative stress and inflammation, thereby suppressing colonic inflammation and alleviating abdominal pain.


Assuntos
Colite , Doenças Inflamatórias Intestinais , Ratos , Animais , Espécies Reativas de Oxigênio/metabolismo , Hidrogênio/farmacologia , Hidrogênio/metabolismo , Água/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , Colo/metabolismo , Ácido Trinitrobenzenossulfônico/toxicidade , Inflamação/metabolismo , Dor Abdominal/etiologia , Colite/induzido quimicamente , Colite/metabolismo
13.
Biochem Biophys Res Commun ; 636(Pt 2): 48-54, 2022 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-36343490

RESUMO

Inflammatory bowel disease (IBD) is a non-specific inflammatory disease of the intestine with the pathogenesis to be largely unknown. We found that microRNA (miR)-10b knock-out mice displayed mild IBD symptoms, suggesting that miR-10b may be involved in the onset and development of IBD. This study focuses on elucidating the role of miR-10b in IBD. The colitis model was induced by feeding the mice with 2.5% dextran sodium sulfate (DSS), and the expression levels of miR-10b in colon tissue and blood samples were examined. The severity of colitis was assessed by disease activity index, colon length, histopathological damage, intestinal permeability and ELISA. Then, after transfection of Caco-2 cells with miR-10b mimic and inhibitor, qRT-PCR was used to detect the expression levels of intestinal barrier related genes in colon tissues and cells. miR-10b levels were significantly reduced in mice with DSS-induced acute colitis. Compared with wild-type (WT) mice, miR-10b knockout mice were more sensitive to DSS-induced colitis characterized by increased inflammatory cell infiltration and more severe disruption of colonic barrier function. In addition, by inhibiting miR-10b and thus increasing intestinal barrier gene expression in Caco-2 cells, we found that miR-10b suppressed inflammatory responses and enhanced intestinal barrier function both in vivo and in vitro. miR-10b inhibits the inflammatory response in DSS-induced acute colitis mice in vivo and enhances intestinal barrier function in vitro, suggesting that miR-10b plays a key role in the developmental process of IBD. Thus, miR-10b may be expected to be a new target for the treatment of IBD.


Assuntos
Colite , Doenças Inflamatórias Intestinais , MicroRNAs , Animais , Humanos , Camundongos , Células CACO-2 , Colite/induzido quimicamente , Colite/genética , Colite/metabolismo , Colo/patologia , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/metabolismo , Mucosa Intestinal/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , MicroRNAs/genética , MicroRNAs/metabolismo
14.
BMJ Case Rep ; 15(11)2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36400721

RESUMO

Two patients with an acute left-sided colonic obstruction had a successful decompression after construction of a blowhole transverse colostomy as a bridge to surgery. However, they presented with two rather unknown stoma-related complications during this bridging period. Patient A had a stomal prolapse with additional skin problems.Patient B complained of abdominal discomfort during follow-up. The blowhole colostomy appeared to be stenotic. Stoma dilation and irrigation was initiated to prevent complete closure.Definite resection of the left-sided obstruction and reversal of both blowhole colostomies was successful, and the patients recovered without further complications.We hypothesise that incision size may be related to prolapse and stenosis rates and that eversion of the mucosa of the blowhole may reduce the risk of stomal stenosis.


Assuntos
Colostomia , Obstrução Intestinal , Humanos , Colostomia/efeitos adversos , Constrição Patológica/etiologia , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Colo/cirurgia , Prolapso
16.
Front Immunol ; 13: 954885, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36341441

RESUMO

Background: Intestinal mucositis is one of the most common and important side effects of 5-fluorouracil (5-FU). Currently, there are still no specific and effective protocols for its prevention and treatment. The aim of the present study was to evaluate the effect of oral administration of Lacticaseibacillus casei (L. casei) on the progression of 5-FU-induced intestinal mucositis. Methods: L. casei (1x109 CFU/ml) or saline was orally administered to Swiss mice, beginning 15 days before intestinal mucositis induction by single intraperitoneal 5-FU administration (450 mg/kg). Body weight, number of peripheral leukocytes and fecal lactic acid bacteria were monitored. After euthanasia, on day 18, tissue samples from colon and each small intestine segment were collected for histopathology. Jejunal tissues were collected and evaluated for iNOS and TNF-alpha immunoexpression, IL-1-beta, IL-6 and TNF-alpha levels, malonaldehyde (MDA) accumulation, invertase activity and factor nuclear kappa B (NFkB-P65) gene expression, toll like receptor-4 (TLR-4), mucin-2 (MUC-2), occludin and zonula occludens-1 (ZO-1). Results: The positive impact of L. casei on 5-FU-induced leukopenia was observed, but not on 5-FU-induced weight loss in mice. L. casei reduced 5-FU-induced inflammation in the colon and small intestine (p<0.05). Decreased TNF-α, IL-1ß, IL-6 (p<0.05) and MDA (p<0.05) levels, as well as decreased iNOS and TNF-alpha protein expressions (p<0.05) were found in the jejunum from L casei group. In addition, L-casei down-regulated NFKB-P65 (p<0.05) and TLR-4 (p<0.05) gene expressions and up-regulated MUC-2 and mucosal barrier proteins occludin and ZO-1 gene expressions (p<0.05). Furthermore, greater lactic acid bacteria population (p<0.05) was found in the L. casei group when compared to control groups. Conclusion: Oral L. casei administration can protect the intestine of Swiss mice from 5-FU-induced intestinal mucositis, thus contributing to overall health.


Assuntos
Lactobacillus casei , Mucosite , Camundongos , Animais , Fluoruracila/farmacologia , Mucosite/induzido quimicamente , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Ocludina/metabolismo , Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , Colo/patologia
17.
J Med Food ; 25(11): 1021-1028, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36322892

RESUMO

This study investigated the effect of perilla oil (PO) on an ulcerative colitis mouse model. Five-week-old male C57BL/6J mice were divided into HD (high-fat diet control), HDD (high-fat diet along with dextran sodium sulfate [DSS] administration), HDD + FO, HDD + PO, and HDD + OO where HDD + FO, HDD + PO, and HDD + OO groups were treated with fish oil (FO), PO, and olive oil (OO), respectively. Biochemical analysis of serum, quantitative polymerase chain reaction, and western blotting of colon tissue were conducted to measure inflammatory marker levels. Administration of DSS resulted in colon shortening and a higher disease activity score than HD group. These symptoms were significantly reversed in the oil-treated groups. The body weight loss after DSS administration was significantly lower in the HDD + PO and HDD + OO groups than in the HDD and HDD + FO groups. PO significantly attenuated the levels of tumor necrosis factor-α, interleukin (IL)-6, and IL-1ß in the serum and colon. The mRNA expression levels of proinflammatory markers in the colon were reduced, whereas those of tight junction proteins and epithelial defense barrier-associated markers were increased by PO treatment. The protein expression of p-p65 was significantly lower in the PO-treated group than the HDD group. In summary, this study revealed that PO improved colitis in the DSS-induced mouse model, indicating its potential role in managing conditions such as ulcerative colitis.


Assuntos
Colite Ulcerativa , Colite , Camundongos , Masculino , Animais , Sulfato de Dextrana/efeitos adversos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colo , Óleos de Peixe/efeitos adversos , Óleos de Peixe/metabolismo , Azeite de Oliva , Modelos Animais de Doenças
18.
Schweiz Arch Tierheilkd ; 164(11): 801-804, 2022 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-36325643

RESUMO

INTRODUCTION: Reports on bovine colon polyps are rare. The present report demonstrates macro- and microscopically hyperplastic colon polyps of a seven-year-old German Simmental cow. Differential diagnoses (adenoma and adenocarcinoma) and aetiology are discussed. Even in cattle, intestinal polyps should be considered as a cause of intussusception.


INTRODUCTION: Les rapports concernant des polypes du colon chez les bovins sont rares. Le présent rapport fait état de polypes du côlon macro- et microscopiquement hyperplasiques chez une vache Simmental allemande de sept ans. Les diagnostics différentiels (adénome et adénocarcinome) et l'étiologie sont discutés. Même chez les bovins, les polypes intestinaux doivent être considérés comme une cause d'invagination.


Assuntos
Adenocarcinoma , Adenoma , Doenças dos Bovinos , Pólipos do Colo , Bovinos , Animais , Pólipos do Colo/diagnóstico , Pólipos do Colo/veterinária , Pólipos do Colo/patologia , Hiperplasia/veterinária , Hiperplasia/patologia , Adenoma/diagnóstico , Adenoma/veterinária , Adenoma/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/veterinária , Adenocarcinoma/patologia , Colo/patologia , Doenças dos Bovinos/diagnóstico , Doenças dos Bovinos/patologia
19.
PLoS Comput Biol ; 18(11): e1010584, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36350878

RESUMO

Organoids have immense potential as ex vivo disease models for drug discovery and personalized drug screening. Dynamic changes in individual organoid morphology, number, and size can indicate important drug responses. However, these metrics are difficult and labor-intensive to obtain for high-throughput image datasets. Here, we present OrganoID, a robust image analysis platform that automatically recognizes, labels, and tracks single organoids, pixel-by-pixel, in brightfield and phase-contrast microscopy experiments. The platform was trained on images of pancreatic cancer organoids and validated on separate images of pancreatic, lung, colon, and adenoid cystic carcinoma organoids, which showed excellent agreement with manual measurements of organoid count (95%) and size (97%) without any parameter adjustments. Single-organoid tracking accuracy remained above 89% over a four-day time-lapse microscopy study. Automated single-organoid morphology analysis of a chemotherapy dose-response experiment identified strong dose effect sizes on organoid circularity, solidity, and eccentricity. OrganoID enables straightforward, detailed, and accurate image analysis to accelerate the use of organoids in high-throughput, data-intensive biomedical applications.


Assuntos
Aprendizado Profundo , Organoides , Colo , Descoberta de Drogas , Sequenciamento de Nucleotídeos em Larga Escala
20.
PLoS One ; 17(11): e0276065, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36350879

RESUMO

BACKGROUND: The aim of the study was to determine the differences in terms of ghrelin presence in the colon between the patients with ulcerative colitis (UC) and control patients. METHODS: Sixty-one UC and 15 control patients were included in the study. Immunohistochemical staining for ghrelin was investigated in colonic biopsy samples of UC and control patients. UC patients were subdivided into Group A (absence of ghrelin staining) and Group B (presence of staining for ghrelin in biopsy samples). Disease activity scores, laboratory parameters and quantitative ghrelin staining were compared in both groups of UC patients, as well as with the observations in control patients. RESULTS: Cells in colonic mucosa stained for ghrelin were identified in twenty-three (37.7%) UC patients, while this proportion in control patients was 6/15(40%). A significant difference was found between Groups A and B for serum albumin concentration but not for erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hemoglobin concentration or leucocyte count. Mayo score/disease activity index (DAI) for UC were significantly higher in Group A than in Group B (p = 0.03). CONCLUSIONS: There were no differences in the amount of colonic ghrelin staining between healthy individuals and UC patients. Colonic ghrelin staining in UC patients seems to be associated with the increased activity of this disease.


Assuntos
Colite Ulcerativa , Humanos , Colite Ulcerativa/patologia , Grelina/metabolismo , Colo/patologia , Sedimentação Sanguínea , Mucosa Intestinal/metabolismo
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