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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 Hazard Mater ; 442: 130010, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36182891

RESUMO

Microplastics (MPs) are ubiquitous in the environment and humans are inevitably exposed to them. However, the effects of MPs in the human digestive environment are largely unknown. The aim of our study was to investigate the impact of repeated exposure to polyethylene (PE) MPs on the human gut microbiota and intestinal barrier using, under adult conditions, the Mucosal Artificial Colon (M-ARCOL) model, coupled with a co-culture of intestinal epithelial and mucus-secreting cells. The composition of the luminal and mucosal gut microbiota was determined by 16S metabarcoding and microbial activities were characterized by gas, short chain fatty acid, volatolomic and AhR activity analyses. Gut barrier integrity was assessed via intestinal permeability, inflammation and mucin synthesis. First, exposure to PE MPs induced donor-dependent effects. Second, an increase in abundances of potentially harmful pathobionts, Desulfovibrionaceae and Enterobacteriaceae, and a decrease in beneficial bacteria such as Christensenellaceae and Akkermansiaceae were observed. These bacterial shifts were associated with changes in volatile organic compounds profiles, notably characterized by increased indole 3-methyl- production. Finally, no significant impact of PE MPs mediated by changes in gut microbial metabolites was reported on the intestinal barrier. Given these adverse effects of repeated ingestion of PE MPs on the human gut microbiota, studying at-risk populations like infants would be a valuable advance.


Assuntos
Microplásticos , Compostos Orgânicos Voláteis , Humanos , Microplásticos/toxicidade , Plásticos/toxicidade , Polietileno/toxicidade , Bactérias , Ácidos Graxos Voláteis , Mucosa Intestinal , Mucinas , Indóis
3.
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
4.
Carbohydr Polym ; 300: 120275, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36372469

RESUMO

Oral delivery is one of the most advantageous routes for drug administration, but due to the short gastrointestinal (GI) residence time, the systemic uptake of poorly absorbed drugs is too low to reach the desired therapeutic effect. In order to prolong the GI residence time of orally given drugs, we synthesized per-thiolated ß-cyclodextrin (CD) as mucoadhesive drug carrier. Due to thiolation, the mucoadhesive properties of CD on porcine intestinal mucosa were increased 2-fold. In vivo studies showed 4 h after oral administration, a 19.4-fold, 2.1- fold, and 4.5-fold higher quantity of per-thiolated ß-CD vs. unmodified ß-CD in the stomach, duodenum/jejunum, and the ileum of rat model, respectively. Eight hours after oral administration, still, 60 % of per-thiolated CD, but no native CD remained in the GI tract. These results provide evidence that due to thiolation of ß-CD, GI-residence time can be essentially prolonged.


Assuntos
Ciclodextrinas , Portadores de Fármacos , Humanos , Suínos , Ratos , Animais , Portadores de Fármacos/farmacologia , Ciclodextrinas/farmacologia , Células CACO-2 , Sistemas de Liberação de Medicamentos/métodos , Compostos de Sulfidrila , Mucosa Intestinal
5.
Chemosphere ; 311(Pt 1): 137048, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36419273

RESUMO

Polyethylene is one of the most important plastic types with the highest consumption in the world. Plastics are prone to photodegradation and turn into microplastics, which are magnified as they move across trophic levels. Microplastics would be able to penetrate into lymph even cross cell membranes, causing harm to the lymphatic and/or circulatory systems, accumulating in secondary organs, and impacting the immune system and cell health. The objective of this study was to test that the activation of the intestinal immune network might be caused by disruption of intestinal microbiota after exposure to different polyethylene microplastics (PE-MPs) concentrations (1, 10, 100, and 1000 µg/mL) in adult zebrafish (Danio rerio) for 7 days. The concentrations of PE-MPs (100 and 1000 µg/mL) exposure decreased the goblet cell coverage. The intestinal microbial diversity index (Shannon and Simpson) was increased at 100 and 1000 µg/mL PE-MPs concentrations. The relative abundance of intestinal dominant microbiota phylum Proteobacteria and Actinobacteria increased significantly (P < 0.05); however, phylum Fusobacteria decreased significantly (P < 0.05). The relative abundance of intestinal microbiota at level of genera showed varying degrees of elevation such as Acinetobacter (6.31-fold), Plesiomonas (4.80-fold), Flavobacterium (10.54-fold) and Pseudomonas (5.17-fold) in 1000 µg/mL PE-MPs. Intestinal innate immunity-complement C3 and C4 content first increased and then declined in a dose-dependent manner. Expression of genes from the intestinal immune network for mucosal immunoglobulin production were increased also in a dose-dependent manner. The expression of immune-related genes (pigr, il10 and ighv4-5) were positively correlated with the relative abundance of genera Plesiomonas. In conclusion, PE-MPs increase the infection probability in the intestinal mucosa by altering the abundance of intestinal dominant microbiota at the level of phylum. PE-MPs exposure activated the intestinal immune network pathway for mucosal immunoglobulin production at a concentration of 100 or 1000 µg/mL for 7 days.


Assuntos
Microplásticos , Polietileno , Animais , Polietileno/toxicidade , Microplásticos/toxicidade , Peixe-Zebra , Plásticos , Mucosa Intestinal , Imunoglobulinas
6.
Biol Pharm Bull ; 45(11): 1720-1724, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36328508

RESUMO

Vitamin D is a fat-soluble micronutrient that plays essential roles in a range of biological processes, including cell proliferation, inflammation, and metabolism. In this study, we investigated the effects of a novel synthetic lithocholic acid derivative with vitamin D activity (Dcha-20) on pharmacokinetic gene expression in human induced pluripotent stem cell-derived intestinal organoids. Compared with vitamin D3 treatment, Dcha-20 was found to upregulate the expression and enzyme activity of the drug-metabolizing enzyme CYP3A4, an indicator of intestinal functional maturation. In addition, Dcha-20 specifically increased expression levels of the xenobiotic detoxification enzyme UGT1A and excretion transporter MRP2. These results suggest that Dcha-20 promotes activity of the intrinsic defense system of the intestinal epithelium.


Assuntos
Células-Tronco Pluripotentes Induzidas , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Organoides , Ácido Litocólico/farmacologia , Ácido Litocólico/metabolismo , Diferenciação Celular , Mucosa Intestinal/metabolismo , Vitamina D/metabolismo , Vitamina D/farmacologia
7.
Intern Med ; 61(21): 3211-3215, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36328586

RESUMO

Mucosal prolapse syndrome (MPS) is a benign inflammatory disease of the rectum that causes bloody stool. Endoscopic treatment for MPS has not been established. We herein report a consecutive case series of endoscopic submucosal dissection (ESD) for MPS. There were four cases treated with ESD alone. All lesions were on the dentate line, and all were polypoid. The median procedure time was 77 minutes. No complications were observed. The median observation period was 1,108 days, and bloody stool and endoscopic recurrence of MPS were not observed.ESD for polypoid-type MPS was an effective treatment for improving bloody stool and suppressing endoscopic recurrence.


Assuntos
Ressecção Endoscópica de Mucosa , Humanos , Ressecção Endoscópica de Mucosa/métodos , Reto/patologia , Endoscopia , Resultado do Tratamento , Síndrome , Prolapso , Estudos Retrospectivos , Mucosa Intestinal/patologia
8.
Nutrients ; 14(21)2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36364889

RESUMO

Intestinal inflammation in inflammatory bowel disease (IBD) is closely linked to nutrition. This study aimed to evaluate associations between nutritional, inflammatory, and intestinal barrier parameters in patients with IBD. We assessed nutritional status, fecal short-chain fatty acid profile, serum cytokine levels, and mRNA expression of enzymes and tight junction proteins in intestinal biopsies obtained from 35 patients, including 11 patients with inactive IBD, 18 patients with active IBD, and six controls. Patients with active IBD were characterized by hypoalbuminemia, fluctuations in body weight, and restriction of fiber-containing foods. In addition, they had significantly reduced levels of isovaleric acid and tended to have lower levels of butyric, acetic, and propionic acids. Patients with active IBD had higher mRNA expression of peroxisome proliferator-activated receptor γ and inducible nitric oxide synthase, and lower mRNA expression of claudin-2 and zonula occludens-1, compared with patients with inactive IBD. Moreover, patients with a body mass index (BMI) of ≥25 kg/m2 had higher median tumor necrosis factor-α levels that those with a lower BMI. We comprehensively evaluated inflammatory parameters in relation to IBD activity and nutritional status. The discrepancies between proinflammatory and anti-inflammatory parameters depending on IBD activity may be related to nutritional factors, including diet and abnormal body weight.


Assuntos
Doenças Inflamatórias Intestinais , Mucosa Intestinal , Humanos , Mucosa Intestinal/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , Inflamação/metabolismo , Peso Corporal , RNA Mensageiro/metabolismo
9.
Nutrients ; 14(21)2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36364929

RESUMO

Obesity is associated with metabolic and physiological effects in the gut. In this study, we evaluated the anti-inflammatory effect of trypsin inhibitor isolated from tamarind seeds (TTI) in vitro (interaction with lipopolysaccharide (LPS) and inhibitory activity against human neutrophil elastase (HNE)), and using intestinal co-cultures of Caco-2:HT29-MTX cell lines inflamed with TNF-α (50 ng/mL) and a Wistar rat model of diet-induced obesity (n = 15). TTI was administered to animals by gavage (10 days), and the treated group (25 mg/kg/day) was compared to animals without treatment or treated with a nutritionally adequate diet. In the in vitro study, it showed inhibitory activity against HNE (93%). In co-cultures, there was no protection or recovery of the integrity of inflamed cell monolayers treated with TTI (1.0 mg/mL). In animals, TTI led to lower plasma concentrations of TNF-α and IL-6, total leukocytes, fasting glucose, and LDL-c (p < 0.05). The intestines demonstrated a lower degree of chronic enteritis, greater preservation of the submucosa, and greater intestinal wall thickness than the other groups (p = 0.042). Therefore, the better appearance of the intestine not reflected in the intestinal permeability added to the in vitro activity against HNE point to possibilities for new studies and applications related to this activity.


Assuntos
Tamarindus , Ratos , Animais , Humanos , Células CACO-2 , Fator de Necrose Tumoral alfa/metabolismo , Mucosa Intestinal/metabolismo , Ratos Wistar , Permeabilidade , Obesidade/tratamento farmacológico , Obesidade/etiologia , Obesidade/metabolismo , Dieta , Intestinos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismo
10.
Nutrients ; 14(21)2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36364961

RESUMO

The epithelial monolayer is the primary determinant of mucosal barrier function, and tight junction (TJ) complexes seal the paracellular space between the adjacent epithelial cells and represent the main "gate-keepers" of the paracellular route. Impaired TJ functionality results in increased permeation of the "pro-inflammatory" luminal contents to the circulation that induces local and systemic inflammatory and immune responses, ultimately triggering and/or perpetuating (chronic) systemic inflammatory disorders. Increased gut leakiness is associated with intestinal and systemic disease states such as inflammatory bowel disease and neurodegenerative diseases such as Parkinson's disease. Modulation of TJ dynamics is an appealing strategy aiming at inflammatory conditions associated with compromised intestinal epithelial function. Recently there has been a growing interest in nutraceuticals, particularly in non-digestible oligosaccharides (NDOs). NDOs confer innumerable health benefits via microbiome-shaping and gut microbiota-related immune responses, including enhancement of epithelial barrier integrity. Emerging evidence supports that NDOs also exert health-beneficial effects on microbiota independently via direct interactions with intestinal epithelial and immune cells. Among these valuable features, NDOs promote barrier function by directly regulating TJs via AMPK-, PKC-, MAPK-, and TLR-associated pathways. This review provides a comprehensive overview of the epithelial barrier-protective effects of different NDOs with a special focus on their microbiota-independent modulation of TJs.


Assuntos
Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Humanos , Junções Íntimas/metabolismo , Oligossacarídeos/farmacologia , Oligossacarídeos/metabolismo , Células Epiteliais , Doenças Inflamatórias Intestinais/metabolismo , Mucosa Intestinal/metabolismo , Permeabilidade
11.
BMC Med ; 20(1): 440, 2022 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-36369023

RESUMO

BACKGROUND: Untreated celiac disease (CD) patients have increased levels of blood glutamine and a lower duodenal expression of glutaminase (GLS). Intestinal gluconeogenesis (IGN) is a process through which glutamine is turned into glucose in the small intestine, for which GLS is crucial. Animal studies suggest impaired IGN may have long-term effects on metabolic control and be associated with the development of type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). The aim of this study was to thoroughly investigate IGN at the gene expression level in children with untreated celiac disease. METHODS: Quantitative polymerase chain reaction (qPCR) was used to quantify the expression of 11 target genes related to IGN using the delta-delta Ct method with three reference genes (GUSB, IPO8, and YWHAZ) in duodenal biopsies collected from 84 children with untreated celiac disease and 58 disease controls. RESULTS: Significantly lower expression of nine target genes involved in IGN was seen in duodenal biopsies from CD patients compared with controls: FBP1, G6PC, GLS, GPT1, PCK1, PPARGC1A, SLC2A2, SLC5A1, and SLC6A19. No significant difference in the expression was observed for G6PC3 or GOT1. CONCLUSIONS: Children with untreated celiac disease have lower expression of genes important for IGN. Further studies are warranted to disentangle whether this is a consequence of intestinal inflammation or due to an impaired metabolic pathway shared with other chronic metabolic diseases. Impaired IGN could be a mechanism behind the increased risk of NAFLD seen in CD patients.


Assuntos
Doença Celíaca , Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Animais , Doença Celíaca/genética , Gluconeogênese/genética , Hepatopatia Gordurosa não Alcoólica/patologia , Glutamina/metabolismo , Diabetes Mellitus Tipo 2/patologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia
12.
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
13.
Ann Med ; 54(1): 3219-3233, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36382627

RESUMO

BACKGROUND: Ulcerative colitis (UC), a chronic inflammatory disease, often cause carcinogenesis, disability, and intestinal perforation. The JingFangFuZiLiZhong formula (JFFZLZ) shows a good effect against UC in the clinic. Hence, we aim to investigate the mechanisms between JFFZLZ and UC via network pharmacology data mining and in vivo experiments. METHODS: We obtained active constituents and related targets from public databases. The overlapped genes between JFFZLZ and UC targets were further analysed by enrichment analysis. The active constituents and hub targets were used to construct molecule docking analysis. We finally screened out nine hub targets and their expressions were verified in the Gene Expression Omnibus database and UC rats' colon tissues after JFFZLZ treatment. RESULTS: The results implied that JFFZLZ mainly regulated signal transduction, metabolites production, and inflammation pathways. The expression of STAT3, CXCL8, IL6, CXCL12, TNF, TP53, and PTPN11 were both upregulated in colon tissues of UC patients and UC rats. While RELA, EGFR, and TP53 were downregulated in UC patients, but upregulated in UC rats. Furthermore, JFFZLZ could repair UC rats' colon mucosal damage and promote the healing of ulcers via regulating the hub targets. CONCLUSION: These results elucidated that the anti-UC effect of JFFZLZ was closely related to the inhibition of inflammatory response, inhibition of oxidative stress, and repairing colon mucosal damage through different signal pathways. The findings could contribute to a better understanding of the regulation mechanisms in JFFZLZ against UC.Key messagesJFFZLZ could reduce the inflammatory infiltration and repair UC rats' colon mucosal damage.Through the network pharmacology-based strategy and public database mining, we obtained the hub targets and key pathways between JFFZLF and UC.The mechanism of JFFZLZ against UC was inhibition of inflammatory response and oxidative stress by regulating the expression of the hub targets.


Assuntos
Colite Ulcerativa , Humanos , Ratos , Animais , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/genética , Farmacologia em Rede , Mucosa Intestinal/metabolismo , Transdução de Sinais
14.
PLoS One ; 17(11): e0277096, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36399482

RESUMO

Vasoactive intestinal peptide (VIP) as a neurocrine factor released by enteric neurons has been postulated to participate in the regulation of transcellular active calcium transport across intestinal epithelium, but the preceding evidence is scant and inconclusive. Herein, transepithelial calcium flux and epithelial electrical parameters were determined by Ussing chamber technique with radioactive tracer in the intestinal epithelium-like Caco-2 monolayer grown on Snapwell. After 3-day culture, Caco-2 cells expressed mRNA of calcium transporters, i.e., TRPV6, calbindin-D9k, PMCA1b and NCX1, and exhibited transepithelial resistance of ~200 Ω cm2, a characteristic of leaky epithelium similar to the small intestine. VIP receptor agonist was able to enhance transcellular calcium flux, whereas VIP receptor antagonist totally abolished calcium fluxes induced by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. Since the intestinal cystic fibrosis transmembrane conductance regulator (CFTR) could be activated by VIP and calciotropic hormones, particularly parathyroid hormone, we sought to determine whether CFTR also contributed to the 1,25(OH)2D3-induced calcium transport. A selective CFTR inhibitor (20-200 µM CFTRinh-172) appeared to diminish calcium fluxes as well as transepithelial potential difference and short-circuit current, both of which indicated a decrease in electrogenic ion transport. On the other hand, 50 µM genistein-a molecule that could rapidly activate CFTR-was found to increase calcium transport. Our in silico molecular docking analysis confirmed direct binding of CFTRinh-172 and genistein to CFTR channels. In conclusion, VIP and CFTR apparently contributed to the intestinal calcium transport, especially in the presence of 1,25(OH)2D3, thereby supporting the existence of the neurocrine control of intestinal calcium absorption.


Assuntos
Cálcio , Regulador de Condutância Transmembrana em Fibrose Cística , Humanos , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Cálcio/metabolismo , Peptídeo Intestinal Vasoativo/farmacologia , Peptídeo Intestinal Vasoativo/metabolismo , Células CACO-2 , Receptores de Peptídeo Intestinal Vasoativo/metabolismo , Genisteína/metabolismo , Simulação de Acoplamento Molecular , Transporte de Íons , Mucosa Intestinal/metabolismo , Cálcio na Dieta/metabolismo
15.
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
16.
Adv Immunol ; 155: 95-131, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36357013

RESUMO

Most antibody produced by humans originates from mucosal B cell responses. The rules, mechanisms, and outcomes of this process are distinct from B cell responses to infection. Within the context of the intestine, we discuss the induction of follicular B cell responses by microbiota, the development and maintenance of mucosal antibody-secreting cells, and the unusual impacts of mucosal antibody on commensal bacteria. Much remains to be learned about the interplay between B cells and the microbiota, but past and present work hints at a complex, nuanced relationship that may be critical to the way the mammalian gut fosters a beneficial microbial ecosystem.


Assuntos
Microbioma Gastrointestinal , Humanos , Animais , Mucosa Intestinal , Imunoglobulina A , Ecossistema , Linfócitos B , Imunidade nas Mucosas , Mamíferos
17.
Georgian Med News ; (328-329): 133-137, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36318857

RESUMO

The state of the microcirculatory bed remains one of the determining factors in course of inflammatory bowel diseases (IBD). The presence of small foci of ischemia could realize in dystrophic-necrobiotic consequences, which can also underlie the development or strengthening of the inflammatory process. Based on above, the goal of our study was to determine the impact of the development of mucosal ischemia in the colon on the activity of proliferative processes during inflammation. The study was performed on 12 adult WAG rats with modeling IBD by oral administration of 2.5% solution Dextran Sulfate Sodium. Serial slides of the colon where made with stained with hematoxylin and eosin, according to Rego, immunohistochemical examination (IHC) to Ki67. Volume of ischemic area and Ki67 expression were detected. Statistical comparison was performed. Inspection microscopy in the DSS experimental group determined alterative-desquamative changes in the surface epithelium and epithelium of intestinal glands (crypt); diffuse polymorphic cellular infiltration in the mucous membrane, which in some places spread to the submucosal base, that are morphological manifestations of IBD. Foci of ischemia had been detected in that group with 13.09±0.67% volume as just microfocal changes were observed in intact animals (p < 0.05). Detection of proliferative activity depending on ischemic signs was realized in different level of Ki67 expression. So, lowest level of Ki67 was estimated in mucosa above ischemia (18.06±3.33%). Most pronounced expression of Ki67 was observed in IBD group in area which no connected with ischemia and was even 57.71±4.68% (p < 0.05). Ki67 was strongly expressed in epithelial cells of the colon both in intact tissue and in modeling IBD with significant increasing expression more than twice in inflammatory group (p < 0.05) but spreading of activity process was uneven. Collation of slides with ICH and Rego staining realized in estimation of strong negative correlation between Ki67 expression and ischemia (r=-0.819).


Assuntos
Doenças Inflamatórias Intestinais , Ratos , Animais , Antígeno Ki-67/metabolismo , Microcirculação , Doenças Inflamatórias Intestinais/metabolismo , Mucosa Intestinal/metabolismo , Isquemia
18.
Cells ; 11(21)2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36359839

RESUMO

Mitochondria-targeted antioxidants have become promising candidates for the therapy of various pathologies. The mitochondria-targeted antioxidant SkQ1, which is a derivative of plastoquinone, has been successfully used in preclinical studies for the treatment of cardiovascular and renal diseases, and has demonstrated anti-inflammatory activity in a number of inflammatory disease models. The present work aimed to investigate the therapeutic potential of SkQ1 and C12TPP, the analog of SkQ1 lacking the antioxidant quinone moiety, in the prevention of sodium dextran sulfate (DSS) experimental colitis and impairment of the barrier function of the intestinal epithelium in mice. DSS-treated animals exhibited weight loss, bloody stool, dysfunction of the intestinal epithelium barrier (which was observed using FITC-dextran permeability), reduced colon length, and histopathological changes in the colon mucosa. SkQ1 prevented the development of clinical and histological changes in DSS-treated mice. SkQ1 also reduced mRNA expression of pro-inflammatory molecules TNF, IL-6, IL-1ß, and ICAM-1 in the proximal colon compared with DSS-treated animals. SkQ1 prevented DSS-induced tight junction disassembly in Caco-2 cells. Pretreatment of mice by C12TPP did not protect against DSS-induced colitis. Furthermore, C12TPP did not prevent DSS-induced tight junction disassembly in Caco-2 cells. Our results suggest that SkQ1 may be a promising therapeutic agent for the treatment of inflammatory bowel diseases, in particular ulcerative colitis.


Assuntos
Antioxidantes , Colite , Humanos , Camundongos , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Células CACO-2 , Modelos Animais de Doenças , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Mucosa Intestinal/patologia , Mitocôndrias/patologia
19.
Cells ; 11(21)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36359856

RESUMO

BACKGROUND: Multiple organ dysfunction syndrome (MODS) occurs in the gastrointestinal tract and injured intestinal mucosa is the anatomical basis for various diseases. The expression of circular RNAs (circRNAs) is implicated in many diseases; however, the role of circRNAs in intestinal mucosal injury is yet to be discovered. Our preliminary gene microarray analysis revealed a novel circular RNA, circMaml2, with a significant intestinal mucosal protection effect. Its expression was found to decrease in severely burned intestinal mucosal tissue, whereas its overexpression might facilitate the reconstruction of the injured intestinal mucous membrane. METHODS: The function of circMaml2 in cell proliferation and migration was studied in MC38 cells. The repair function of circMaml2 was tested on the intestinal mucosa of mice. RNA-binding protein polypyrimidine tract-binding protein 1(PTBP1) was selected by pull-down assay and mass spectrometry (MS). RNA immunoprecipitation (RIP) was performed to confirm the binding of circMaml2 and PTBP1 and to study PTBP1 and its downstream target, early B-cell factor 1(Ebf1). Bioinformatics software forecast analysis and dual-luciferase reporter assay were performed to ascertain miR-683 and Sec62 as the downstream targets of circMaml2 and miR-683, respectively. Furthermore, PRP8 was discovered to promote the biogenesis of circMaml2. RESULTS: CircMaml2 promotes cell proliferation and migration of MC38 cells and the repair of the intestinal mucosa of mice. This effect is brought about by combining with PTBP1 to improve Ebf1 and interacting with miR-683 to regulate Sec2. Furthermore, PRP8 was discovered to promote the biogenesis of circMaml2. CONCLUSIONS: This is the first reported study of the effect of circMaml2 on intestinal mucosal repair.


Assuntos
MicroRNAs , Proteína de Ligação a Regiões Ricas em Polipirimidinas , Camundongos , Animais , Proteína de Ligação a Regiões Ricas em Polipirimidinas/genética , Proteína de Ligação a Regiões Ricas em Polipirimidinas/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas/genética , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , RNA Circular/genética , Fatores de Transcrição/metabolismo , MicroRNAs/genética , Mucosa Intestinal/metabolismo
20.
J Cell Sci ; 135(21)2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36349897

RESUMO

The intestine, a rapidly self-renewing organ, is part of the gastrointestinal system. Its major roles are to absorb food-derived nutrients and water, process waste and act as a barrier against potentially harmful substances. Here, we will give a brief overview of the primary functions of the intestine, its structure and the luminal gradients along its length. We will discuss the dynamics of the intestinal epithelium, its turnover, and the maintenance of homeostasis. Finally, we will focus on the characteristics and functions of intestinal mesenchymal and immune cells. In this Cell Science at a Glance article and the accompanying poster, we aim to present the most recent information about gut cell biology and physiology, providing a resource for further exploration.


Assuntos
Mucosa Intestinal , Nutrientes , Homeostase/fisiologia
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