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1.
J Pharmacol Sci ; 150(2): 90-93, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36055756

RESUMO

The purpose of this study was to investigate how disease state of the UC and CD patients affect tissue function determined from electrophysiology viewpoint the electrophysiological parameters on normal, ulcerative colitis (UC) and Crohn's disease (CD) patients. Potential differences (PD), short circuit current (Isc) and resistance (R) as electrophysiological parameters were determined using human large intestinal tissues. The measure of autoptical abnormality was quantified on an arbitrary scale of 0-2. A severe effect of ulcer and thickened mucosa by fibrosis was scored as Grade 2. The larger number of autopsy grade on both UC and CD tissues, the lower values of PD and R than those of normal tissues were observed, although Isc values were not statistically changed irrespective of autopsy grade. This electrophysiological observation of reduced PD indicated functional impairment of active ion transport via ion pumps. Additionally, the R values of CD tissues on each autopsy grade tended to be lower than those of UC tissues. These results suggest that the effect of inflammatory bowel disease on barrier function is different between UC and CD tissues. Therefore, the fibrosis on CD patients might affect the electrophysiological parameters than that of UC patients.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doença de Crohn/patologia , Fibrose , Humanos , Mucosa Intestinal/patologia , Intestinos
3.
World J Gastroenterol ; 28(24): 2636-2653, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35979165

RESUMO

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders of the intestinal tract that have emerged as a growing problem in industrialized countries. Knowledge of IBD pathogenesis is still incomplete, and the most widely-accepted interpretation considers genetic factors, environmental stimuli, uncontrolled immune responses and altered intestinal microbiota composition as determinants of IBD, leading to dysfunction of the intestinal epithelial functions. In vitro models commonly used to study the intestinal barrier do not fully reflect the proper intestinal architecture. An important innovation is represented by organoids, 3D in vitro cell structures derived from stem cells that can self-organize into functional organ-specific structures. Organoids may be generated from induced pluripotent stem cells or adult intestinal stem cells of IBD patients and therefore retain their genetic and transcriptomic profile. These models are powerful pharmacological tools to better understand IBD pathogenesis, to study the mechanisms of action on the epithelial barrier of drugs already used in the treatment of IBD, and to evaluate novel target-directed molecules which could improve therapeutic strategies. The aim of this review is to illustrate the potential use of organoids for therapy personalization by focusing on the most significant advances in IBD research achieved through the use of adult stem cells-derived intestinal organoids.


Assuntos
Células-Tronco Pluripotentes Induzidas , Doenças Inflamatórias Intestinais , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Mucosa Intestinal/patologia , Intestinos/patologia , Organoides
4.
Sci Rep ; 12(1): 13447, 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35927305

RESUMO

Various omics-based biomarkers related to the occurrence, progression, and prognosis of colorectal cancer (CRC) have been identified. In this study, we attempted to identify gut microbiome-based biomarkers and detect their association with host gene expression in the initiation and progression of CRC by integrating analysis of the gut mucosal metagenome, RNA sequencing, and sociomedical factors. We performed metagenome and RNA sequencing on colonic mucosa samples from 13 patients with advanced CRC (ACRC), 10 patients with high-risk adenoma (HRA), and 7 normal control (NC) individuals. All participants completed a questionnaire on sociomedical factors. The interaction and correlation between changes in the microbiome and gene expression were assessed using bioinformatic analysis. When comparing HRA and NC samples, which can be considered to represent the process of tumor initiation, 28 genes and five microbiome species were analyzed with correlation plots. When comparing ACRC and HRA samples, which can be considered to represent the progression of CRC, seven bacterial species and 21 genes were analyzed. When comparing ACRC and NC samples, 16 genes and five bacterial species were analyzed, and four correlation plots were generated. A network visualizing the relationship between bacterial and host gene expression in the initiation and progression of CRC indicated that Clostridium spiroforme and Tyzzerella nexilis were hub bacteria in the development and progression of CRC. Our study revealed the interactions of and correlation between the colonic mucosal microbiome and host gene expression to identify potential roles of the microbiome in the initiation and progression of CRC. Our results provide gut microbiome-based biomarkers that may be potential diagnostic markers and therapeutic targets in patients with CRC.


Assuntos
Adenoma , Neoplasias Colorretais , Microbioma Gastrointestinal , Microbiota , Adenoma/genética , Adenoma/microbiologia , Bactérias/genética , Neoplasias Colorretais/patologia , Microbioma Gastrointestinal/genética , Expressão Gênica , Humanos , Mucosa Intestinal/patologia , Microbiota/genética
5.
Georgian Med News ; (327): 18-26, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35959928

RESUMO

The main purpose of the study is to determine peculiar morphological characteristics of structural changes of alimentary system organs in the case of experimental undifferentiated dysplasia of connective tissue (UDCT). Intranatal antigen introduction was conducted as an experimental model of UDCT. Objects of investigation - pharynx, duodenum, ileum, caecum, ascendant colon of white rats from the first up to the 60th day of postnatal life. Animals were contained in standard conditions of vivarium according to Law of Ukraine № 1759-VI (15.12.2009) On the Protection of Animals from Cruelty. Morphological structure of organs were examined at days 1st, 7th, 14th, 21th, 45th, 60th after birth. Morphometric, histological, histochemical, lectinistochemical, immunehistochemic and statistic methods were used. Analysis of the obtained results was conducted by means of statistical methods with the use of computer license program «Statistica for Windows 13¼ (StatSoft Inc., № JPZ804I382130ARCN10-J). The compared results considered such, that for certain differ at р<0,05 that is generally accepted for biological and medical researches. On the background of experimental syndrome of UDCT, developed by intranatal antigen loading, it is settled that the number of intraepithelial lymphocytes, number of lymphocytes of submucose layer of alimentary tract increases. Ratio between cells of mucosa (including epithelial layer and submucosal layer) changes. Interrelation between layers of alimentary tube changes resulting in the thickening of mucosa (including epithelial layer and submucosal layer) and thinning of muscular layer. These inflections result in elongation of duodenum, small and large intestines. Throughout the first month after birth in rats with experimental syndrome of UDCT lymphocyte/epitheliocyte, lymphocyte/ fibroblast and lymphocyte/mitosis indexes change in proximal and distal parts of digestive tract.


Assuntos
Tecido Conjuntivo , Duodeno , Intestino Grosso , Animais , Colo , Tecido Conjuntivo/patologia , Duodeno/patologia , Íleo , Mucosa Intestinal/patologia , Intestino Grosso/patologia
6.
Turk J Gastroenterol ; 33(8): 710-719, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35943149

RESUMO

BACKGROUND: This study aimed to examine the effect of sodium butyrate on severe acute pancreatitis-related gut barrier injury in a rat model and explore its mechanism. METHODS: Male rats randomly fell into 3 groups, that is, the control, the severe acute pancreatitis group, and the severe acute pancreatitis+butyrate group. Rats in the control group received sham operation, while rats in the severe acute pancreatitis group and severe acute pancreatitis+butyrate group received severe acute pancreatitis induction by intraductal infusion of 4% sodium taurocholate. After that, rats in the severe acute pancreatitis+butyrate group were fed with sodium butyrate solution with free access. Intestinal barrier injury was measured based on the expression of tight junction proteins by reverse transcription polymerase chain reaction, Western blotting assay as well as immunohistochemical staining. The variation of Treg cells was measured by reverse transcription polymerase chain reaction, Western blotting assay, immunohistochemical staining, and flow cytometry analysis. RESULTS: Compared to rats in the control, rats in the severe acute pancreatitis group showed significantly higher pathohistological scores (P < .001) in the intestine, as well as decreased expression of occludin and ZO-1. While, rats in the severe acute pancreatitis+butyrate group showed mitigated histologic lesions (P < .05) and increased expressions of occludin and ZO-1. In addition, rats in the severe acute pancreatitis group showed the obvious reduction in the expressions of Foxp3 and GPR109a and the decreased percentage of Treg cells in the intestine (P < .001) compared to rats in the control. However, rats in the severe acute pancreatitis+butyrate group showed markedly increased expressions of Foxp3 and GPR109a and the upregulated percentage of Treg cells (P < .01). CONCLUSION: Butyrate could significantly mitigate the intestinal injury induced by severe acute pancreatitis, probably by inducing the differentiation of Treg cells.


Assuntos
Pancreatite , Doença Aguda , Animais , Ácido Butírico/efeitos adversos , Ácido Butírico/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Mucosa Intestinal/patologia , Masculino , Ocludina/metabolismo , Ocludina/farmacologia , Pancreatite/induzido quimicamente , Pancreatite/tratamento farmacológico , Ratos , Linfócitos T Reguladores/metabolismo
7.
Cells ; 11(13)2022 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-35805133

RESUMO

Irritable bowel syndrome (IBS) is a disorder of brain-gut interaction characterised by abdominal pain and changes in bowel habits. In the diarrhoea subtype (IBS-D), altered epithelial barrier and mucosal immune activation are associated with clinical manifestations. We aimed to further evaluate plasma cells and epithelial integrity to gain understanding of IBS-D pathophysiology. One mucosal jejunal biopsy and one stool sample were obtained from healthy controls and IBS-D patients. Gastrointestinal symptoms, stress, and depression scores were recorded. In the jejunal mucosa, RNAseq and gene set enrichment analyses were performed. A morphometric analysis by electron microscopy quantified plasma cell activation and proximity to enteric nerves and glycocalyx thickness. Immunoglobulins concentration was assessed in the stool. IBS-D patients showed differential expression of humoral pathways compared to controls. Activation and proximity of plasma cells to nerves and IgG concentration were also higher in IBS-D. Glycocalyx thickness was lower in IBS-D compared to controls, and this reduction correlated with plasma cell activation, proximity to nerves, and clinical symptoms. These results support humoral activity and loss of epithelial integrity as important contributors to gut dysfunction and clinical manifestations in IBS-D. Additional studies are needed to identify the triggers of these alterations to better define IBS-D pathophysiology.


Assuntos
Síndrome do Intestino Irritável , Diarreia/complicações , Glicocálix/metabolismo , Humanos , Mucosa Intestinal/patologia , Síndrome do Intestino Irritável/complicações , Fibras Nervosas/patologia , Plasmócitos/metabolismo
8.
Aliment Pharmacol Ther ; 56 Suppl 1: S73-S85, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35815825

RESUMO

Classically considered a disease of early childhood characterised by malabsorption and failure to thrive, coeliac disease is now recognised to arise in genetically susceptible individuals at any age. Although permissive HLA genotypes are the strongest predictor of coeliac disease, they are not sufficient. Several prospective cohort studies enrolling genetically at-risk infants have investigated the role of potential triggers of coeliac disease autoimmunity, such as timing of gluten introduction, viral infections and dietary patterns. Much less is known about triggers of coeliac disease in adulthood. Better understanding of factors leading to coeliac disease may be helpful in the management of those with potential coeliac disease (elevated serum celiac antibodies without villous atrophy in the small intestine), many of whom initiate a gluten-free diet without demonstration of villous atrophy. There are a range of clinical presentations of celiac disease in childhood and patterns of coeliac serology, including fluctuation and spontaneous reversion on a gluten-containing diet, vary. There is a current debate over best strategies to manage adults and children with potential coeliac disease to avoid over-treatment and under-treatment. Childhood and adolescence carry unique issues pertaining to the diagnosis and management of coeliac disease, and include nutrition and growth, rescreening, repeat biopsy, dietary adherence concerns and transition to adult care. In conclusion, while coeliac disease has similar pathogenesis and general clinical manifestations in paediatric and adult populations, diagnostic and management approaches need to adapt to the developmental stages.


Assuntos
Doença Celíaca , Adolescente , Adulto , Atrofia/patologia , Doença Celíaca/diagnóstico , Doença Celíaca/terapia , Criança , Pré-Escolar , Dieta Livre de Glúten , Glutens , Humanos , Lactente , Mucosa Intestinal/patologia , Estudos Prospectivos
9.
Am J Physiol Gastrointest Liver Physiol ; 323(3): G205-G218, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35819158

RESUMO

Feeding modes influence the gut microbiome, immune system, and intestinal barrier homeostasis in neonates; how feeding modes impact susceptibility to neonatal gastrointestinal (GI) diseases is still uncertain. Here, we investigated the impact of dam feeding (DF) and formula feeding (FF) on features of the gut microbiome and physiological inflammation during the first 2 days of postnatal development and on the susceptibility to intestinal injury related to the inflammatory state in neonatal mouse pups. 16S rRNA sequencing data revealed microbiome changes, lower α-diversity, and a distinct pattern of ß-diversity including expansion of f_Enterobacteriaceae and f_Enterococcaceae in the ileum of FF pups compared with DF pups by postnatal day (P)2. Together with gut dysbiosis, the FF cohort also had greater ileal mucosa physiological inflammatory activity compared with DF pups by P2 but maintained normal histological features. Interestingly, FF but not DF mouse pups developed necrotizing enterocolitis (NEC)-like intestinal injury within 24 h after anti-CD3 mAb treatment, suggesting that FF influences the susceptibility to intestinal injury in neonates. We further found that NEC-like incidence in anti-CD3 mAb-treated FF neonatal pups was attenuated by antibiotic treatment. Collectively, our data suggest that FF predisposes mouse pups to anti-CD3 mAb-induced intestinal injury due to abnormal f_Enterobacteriaceae and f_Enterococcaceae colonization. These findings advance our understanding of FF-associated microbial colonization and intestinal inflammation, which may help inform the development of new therapeutic approaches to GI diseases like NEC in infants.NEW & NOTEWORTHY This report shows that a feeding mode profoundly affects gut colonization in neonatal mice. Furthermore, our results demonstrate that formula feeding predisposes mouse pups to anti-CD3 mAb-induced necrotizing enterocolitis (NEC)-like intestinal injury upon inadequate microbial colonization. The study suggests the role of the combined presence of formula feeding-associated dysbiosis and mucosal inflammation in the pathogenesis of NEC and provides a new mouse model to study this disease.


Assuntos
Enterocolite Necrosante , Microbioma Gastrointestinal , Animais , Animais Recém-Nascidos , Disbiose , Enterocolite Necrosante/tratamento farmacológico , Humanos , Inflamação/patologia , Mucosa Intestinal/patologia , Camundongos , RNA Ribossômico 16S
10.
Contrast Media Mol Imaging ; 2022: 3757763, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35845725

RESUMO

Research Purposes. Inflammatory bowel disease (IBD) is an autoimmune disease coinduced by genes, environment, and immune response, mainly including ulcerative colitis (UC) and Crohn's disease (CD). There are a large number and variety of intestinal bacteria in the human intestinal tract. These bacteria maintain a balance with the human environment and participate in the normal physiological processes of the human body. They play a unique role in defending against pathogen invasion, maintaining the homeostasis of the human immune system and metabolizing substances. Intestinal flora imbalance may be one of the pathogenic factors of IBD, and restoring the disturbed intestinal flora has become a research hotspot in the prevention and treatment of IBD. Changyanning is mainly composed of Dijincao grass, yellow hairy ear grass, camphor tree roots, maple leaves, and so on. Clinical studies have shown that Changyanning alone or in combination has a significant effect on ulcerative colitis, but the treatment mechanism is not yet clear. In this study, we established an IBD animal model to explore the therapeutic mechanism of Changyanning on inflammatory bowel disease and its effect on intestinal flora. Research Methods. Male C57BL/6 SPF mice were given free access to 4% dextran sulfate sodium (DSS) solution for 7 days to establish an ulcerative colitis model. After the model was established, different doses of Changyanning tablets, Changyanning granules, and sulfasalazine were given by gavage for 7 days. The relieving effects of the above drugs on the symptoms of inflammatory bowel disease were evaluated by evaluating the mouse/rat body weight, survival rate, disease activity index, colon length, pathological tissue score, and other indicators. Results. The DSS-induced IBD mouse model showed significant increases in weight loss, DAI score, and pathological score. Both Changyanning tablets and granules can relieve the weight loss of mice, restore the colon length, and protect the colon tissue structure of mice. In reducing DAI and pathological scores in mice, Changyanning granules had a better effect. In conclusion, Changyanning can significantly improve the quality of life of IBD model animals, relieve intestinal inflammatory response, and relieve colonic edema, ulceration, and necrosis. The results show that Changyanning has a certain therapeutic effect on IBD. This study also provides experimental evidence for the application of Changyanning in the treatment of IBD, which is of great significance to its clinical application. The trail is registered in ChiCTR with number (TRN) ChiCTR2000028830.


Assuntos
Colite Ulcerativa , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Citocinas , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Qualidade de Vida , Ratos , Redução de Peso
11.
Cesk Patol ; 58(2): 88-99, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35882543

RESUMO

Duodenum is currently the most popular site to obtain samples of intestinal mucosa for recognition of a disorder leading to malabsorption. Although there are significant overlaps between histological findings described in various non-neoplastic diseases of the duodenum, recognition of one of the six basic morphologic patterns, namely coeliac disease-like pattern, active chronic duodenitis, acute GvHD-like pattern, enteritis with predominant eosinophilic infiltration, enteritis with predominant infiltration by macrophages, and non-inflammatory enteropathy, usually allows diagnostic separation, especially if subtle histological details, clinical setting and serological investigation are taken into account.


Assuntos
Doença Celíaca , Duodenite , Enterite , Biópsia , Doença Celíaca/diagnóstico , Doença Celíaca/patologia , Duodenite/diagnóstico , Duodenite/patologia , Duodeno/patologia , Enterite/diagnóstico , Enterite/patologia , Humanos , Mucosa Intestinal/patologia
12.
Nature ; 607(7919): 563-570, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35831502

RESUMO

Gut commensal bacteria with the ability to translocate across the intestinal barrier can drive the development of diverse immune-mediated diseases1-4. However, the key factors that dictate bacterial translocation remain unclear. Recent studies have revealed that gut microbiota strains can adapt and evolve throughout the lifetime of the host5-9, raising the possibility that changes in individual commensal bacteria themselves over time may affect their propensity to elicit inflammatory disease. Here we show that within-host evolution of the model gut pathobiont Enterococcus gallinarum facilitates bacterial translocation and initiation of inflammation. Using a combination of in vivo experimental evolution and comparative genomics, we found that E. gallinarum diverges into independent lineages adapted to colonize either luminal or mucosal niches in the gut. Compared with ancestral and luminal E. gallinarum, mucosally adapted strains evade detection and clearance by the immune system, exhibit increased translocation to and survival within the mesenteric lymph nodes and liver, and induce increased intestinal and hepatic inflammation. Mechanistically, these changes in bacterial behaviour are associated with non-synonymous mutations or insertion-deletions in defined regulatory genes in E. gallinarum, altered microbial gene expression programs and remodelled cell wall structures. Lactobacillus reuteri also exhibited broadly similar patterns of divergent evolution and enhanced immune evasion in a monocolonization-based model of within-host evolution. Overall, these studies define within-host evolution as a critical regulator of commensal pathogenicity that provides a unique source of stochasticity in the development and progression of microbiota-driven disease.


Assuntos
Bactérias , Translocação Bacteriana , Evolução Biológica , Microbioma Gastrointestinal , Fígado , Bactérias/genética , Bactérias/imunologia , Bactérias/patogenicidade , Translocação Bacteriana/genética , Parede Celular/genética , Enterococcus/genética , Enterococcus/imunologia , Microbioma Gastrointestinal/genética , Genômica , Interações Hospedeiro-Patógeno/imunologia , Humanos , Inflamação/microbiologia , Inflamação/patologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Lactobacillus reuteri/genética , Lactobacillus reuteri/imunologia , Fígado/microbiologia , Fígado/patologia , Linfonodos/microbiologia , Mutação , Processos Estocásticos , Simbiose/genética , Simbiose/imunologia
13.
Arkh Patol ; 84(4): 13-19, 2022.
Artigo em Russo | MEDLINE | ID: mdl-35880595

RESUMO

OBJECTIVE: To determine immunohistochemical features of IgG4-related disease in patients with inflammatory bowel diseases (IBD). MATERIAL AND METHODS: Immunohistochemical testing of colonic biopsy material from 35 patients with IBD (24 cases of ulcerative colitis and 11 cases of Crohn's disease) was carried out using IgG, IgG4 and CD138 antibodies. The number of IgG4- and CD138-positive cells was counted in high power field of microscope (×400). Patient selection was random. RESULTS: IgG4-positive cells were detected in the colonic mucosa of 5 patients with ulcerative colitis. The age of the patients ranged from 24 to 47 years. Two patients had a total, and three had a left-sided lesion of the colon. The anamnesis of the disease ranged from 3 to 13 years. The number of positively stained cells in the reaction with the antibody to IgG4 varied from 2 to 50 in high power field of microscope. We were able to detect over 10 IgG4-positive cells in 3 females aged 28, 30 and 31 years with a long history of ulcerative colitis (5, 4 and 3 years, respectively). Two patients had a total lesion of the colon, all three had an exacerbation of the disease, and a morphological study revealed chronic diffuse active erosive colitis. A high degree of histological activity and pronounced diffuse basal plasmacytosis were noted. In one of the cases, the infiltrate captured the muscular lamina of the mucosa and areas of the submucosa. CONCLUSIONS: IgG4-positive cells in the inflammatory infiltrate, including those with an excess of more than 10 in the field of view of the microscope at high magnification, can be observed in patients with ulcerative colitis with severe and prolonged course of the disease. To classify this colitis as a manifestation of an IgG4-related disease, the results of immunohistochemical studies alone are not enough. It is required to accumulate a larger number of observations, as well as to search for other diagnostic criteria for an IgG4-related disease in these patients.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doença Relacionada a Imunoglobulina G4 , Doenças Inflamatórias Intestinais , Colite Ulcerativa/patologia , Colo/patologia , Doença de Crohn/patologia , Feminino , Humanos , Imunoglobulina G , Doença Relacionada a Imunoglobulina G4/patologia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/diagnóstico , Mucosa Intestinal/patologia
14.
Eur J Gastroenterol Hepatol ; 34(10): 993-999, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35830366

RESUMO

BACKGROUND: Ulcerative colitis is a chronic and progressive inflammatory disorder. The regulator of the G-protein signaling (RGS) is involved in the pathogenesis of several immune system disorders. RGS16, a member of the RGS protein superfamily, has been shown to play critical roles in several immune system-related diseases. However, the roles of RGS16 in ulcerative colitis remain to be elucidated. METHODS: We analyzed the expression of RGS16 in peripheral blood mononuclear cells (PBMCs) and inflamed mucosa of ulcerative colitis patients using quantitative reverse transcription-PCR, western blotting and immunohistochemistry. We performed Spearman's correlation to analyze the correlation between RGS16 expression and the ulcerative colitis endoscopic index of severity (UCEIS), Mayo index, erythrocyte sedimentation rate (ESR) and serum tumor necrosis factor alpha (TNF-a) and IL-17A levels. Further, PBMCs were stimulated with inflammatory cytokines in vitro . RESULTS: RGS16 expression significantly increased in the colonic mucosa and PBMCs from patients with ulcerative colitis and significantly correlated with the Mayo index, UCEIS, ESR and serum TNF-α and IL-17A levels. TNF-α upregulated RGS16 expression in PBMCs in a dose- and time-dependent manner via the nuclear factor kappa beta (NF-kB) signaling pathway. Moreover, anti-TNF treatment with infliximab significantly decreased RGS16 expression in PBMCs and intestinal mucosa of patients with ulcerative colitis. CONCLUSION: Our study revealed a novel mechanism by which RGS16 expression in ulcerative colitis is positively correlated with disease activity. Thus, RGS16 might serve as a potential therapeutic marker for the treatment of ulcerative colitis.


Assuntos
Colite Ulcerativa , Proteínas RGS , Colite Ulcerativa/patologia , Humanos , Inflamação/patologia , Interleucina-17/sangue , Mucosa Intestinal/patologia , Leucócitos Mononucleares , Proteínas RGS/metabolismo , Inibidores do Fator de Necrose Tumoral , Fator de Necrose Tumoral alfa/sangue
15.
J Transl Med ; 20(1): 309, 2022 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-35794599

RESUMO

BACKGROUND: Bacterial translocation was observed in critical illness and patients with chronic diseases such as liver cirrhosis and chronic kidney disease (CKD). Hypokalemia is a common complication in these diseases. Whether low potassium diet may increase intestinal permeability and result in bacterial translocation lack of evidence. The present study was aimed to investigate the potential effects of LK on intestinal permeability. METHODS: Grade 8-week-old male Bal B/C mice were randomly placed either on a normal potassium (NK) mouse chow or a low potassium (LK) diet for 28 days. Intestinal permeability and expression of tight junction proteins were compared between the two groups. RESULTS: Compared with the NK group, the mice in LK group had significantly lower serum potassium level, increased levels of plasmas endotoxin and plasma D-lactate. The bacterial translocation was higher and in occurred mainly in mesenteric lymph nodes (MLN), liver and spleen. The pathologic change of small intestine was obvious with thinner villus lamina propria, shorter crypt depth and thinner intestinal wall. Slight increases in the expression of proteins and mRNA levels of both claudin-1 and claudin-2 were observed in LK group. CONCLUSIONS: Low potassium diet could increase intestinal permeability and thereby lead to bacterial translocation, which was suspected to result from impaired intestinal epithelial barrier and biological barrier.


Assuntos
Translocação Bacteriana , Intestinos , Animais , Mucosa Intestinal/patologia , Intestinos/patologia , Masculino , Camundongos , Permeabilidade , Potássio/metabolismo , Potássio/farmacologia
16.
Pol J Pathol ; 73(1): 50-59, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35848481

RESUMO

Alterations of PD1/PD-L1 pathway may be associated with an excessive inflammatory response in the intestinal wall in inflammatory bowel diseases (IBD). To evaluate the expression of PD-1 and PD-L1 in 4 compartments of intestinal wall (mucosa, submucosa, muscularis propria and lymphatic follicles), high-resolution immunohistochemically stained slides were obtained from formalin-fixed paraffin-embedded samples of 10 Crohn's disease (CD), 9 ulcerative colitis (UC) and 10 unaffected individuals cases. The levels of expression were quantified using the QuPath software. PD-1 was detected in lymphatic follicles in affected and unaffected tissue samples and in inflammatory infiltration in IBD. There was no difference between groups neither in PD-1 overall expression nor in individual compartments, with the exception of the mucosal expression. It was higher in the mucosa of CD patients comparing to controls, however this difference was marginal (p = 0.0461). PD-L1 was expressed in endothelium and mesenteric nervous plexi, consistently in each group. There were no significant differences in PD-L1 immunoreactivity in context of histologic compartment nor clinical diagnosis. The results suggest that PD-1 and PD-L1 expression in intestinal tissue is heterogeneous in the analysed groups, thus it may be dependent on individual characteristics.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Antígeno B7-H1/metabolismo , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Doença de Crohn/metabolismo , Doença de Crohn/patologia , Humanos , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Projetos Piloto , Receptor de Morte Celular Programada 1/metabolismo
17.
Comput Math Methods Med ; 2022: 5927384, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35860188

RESUMO

Background: Ulcerative colitis (UC) is a kind of inflammatory bowel disease which is needed to be predicted. Objective: To analyze various animal models of UC conditions and summarizes the animal selection, model progression, and pathogenic mechanisms of UC animal models. Methods: We surveyed the research papers published in PubMed, Google Scholar, Baidu Scholar, CNKI, SciFinder, and Web of Science in the past 5 years and discussed the experimental animals, modeling methods, and pathogenic mechanisms. Results: In the selection of experimental animals, rats are considered the best experimental animals. The mainstream modeling methods can be categorized into the chemical stimulation method, immune stimulation method, and compound method, among which the compound method is the most successful. In the study of the pathogenesis of UC, the pathogenesis of UC is due to various pathogenic factors, such as nitric oxide (NO), prostaglandins (PG), proinflammatory factors (IL, TNF-α), and intestinal flora. Conclusion: The method of building an animal model of UC is well-established, providing a more targeted selection of animal models for future related experiments.


Assuntos
Colite Ulcerativa , Animais , Colite Ulcerativa/etiologia , Colite Ulcerativa/patologia , Modelos Animais de Doenças , Mucosa Intestinal/patologia , Ratos , Fator de Necrose Tumoral alfa
18.
Tech Coloproctol ; 26(9): 713-723, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35648263

RESUMO

BACKGROUND: Assessment of mucosal healing is important for the management of patients with inflammatory bowel disease (IBD), but endoscopy can miss microscopic disease areas that may relapse. Histological assessment is informative, but no single scoring system is widely adopted. We previously proposed an eight-item histological scheme for the easy, fast reporting of disease activity in the intestine. The aim of the present study was to evaluate the performance of our Simplified Histologic Mucosal Healing Scheme (SHMHS). METHODS: Between April and May 2021 pathologists and gastroenterologists in Italy were invited to contribute to this multicenter study by providing data on single endoscopic-histological examinations for their IBD patients undergoing treatment. Disease activity was expressed using SHMHS (maximum score, 8) and either Simple Endoscopic Score for Crohn's Disease (categorized into grades 0-3) or Mayo Endoscopic Subscore (range 0-3). RESULTS: Thirty hospitals provided data on 597 patients (291 Crohn's disease; 306 ulcerative colitis). The mean SHMHS score was 2.96 (SD = 2.42) and 66.8% of cases had active disease (score ≥ 2). The mean endoscopic score was 1.23 (SD = 1.05), with 67.8% having active disease (score ≥ 1). Histologic and endoscopic scores correlated (Spearman's ρ = 0.76), and scores for individual SHMHS items associated directly with endoscopic scores (chi-square p < 0.001, all comparisons). Between IBD types, scores for SHMHS items reflected differences in presentation, with cryptitis more common and erosions/ulcerations less common in Crohn's disease, and the distal colon more affected in ulcerative colitis. CONCLUSIONS: SHMHS captures the main histological features of IBD. Routine adoption may simplify pathologist workload while ensuring accurate reporting for clinical decision making.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Doença Crônica , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/patologia , Endoscopia Gastrointestinal , Humanos , Mucosa Intestinal/patologia , Índice de Gravidade de Doença
19.
Am J Physiol Gastrointest Liver Physiol ; 323(2): G134-G143, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35726867

RESUMO

Mucosal microbiota differ significantly from fecal microbiota and may play a different role in the pathophysiology of irritable bowel syndrome (IBS). The aims of this study were to determine if the composition of mucosal microbiota differed between IBS, or IBS bowel habit (BH) subtypes, and healthy controls (HCs). Sigmoid colon mucosal biopsies were obtained from 97 Rome-positive patients with IBS (28% IBS-constipation, 38% IBS-diarrhea, 24% IBS-mixed, and 10% IBS-unsubtyped) and 54 HCs, from which DNA was extracted. 16S rRNA gene sequencing and microbial composition analysis were performed. Group differences in α and ß diversity and taxonomic level differences were determined using linear regression while controlling for confounding variables. IBS BH subtype was associated with microbial α diversity (P = 0.0003) with significant differences seen in the mucosal microbiota of IBS-constipation versus IBS-diarrhea (P = 0.046). There were no significant differences in α or ß diversity in the mucosal microbiota of IBS versus HCs (P = 0.29 and 0.93, respectively), but metagenomic profiling suggested functional differences. The relative abundance of Prevotella_9 copri within IBS was significantly correlated with increased abdominal pain (r = 0.36, P = 0.0003), which has not been previously reported in IBS. Significant differences in the mucosal microbiota were present within IBS BH subtypes but not between IBS and HCs, supporting the possibility of IBS BH subtype-specific pathogenesis. Increased Prevotella copri may contribute to symptoms in patients with IBS.NEW & NOTEWORTHY Gut mucosal microbiota differs significantly from fecal microbiota in irritable bowel syndrome (IBS) and may play a different role in its pathophysiology. Investigation of colonic mucosal microbiota in the largest cohort of patients with IBS and healthy controls accounting for confounding variables, including diet demonstrated significant differences in mucosal microbiota between IBS bowel habit subtypes but not between IBS and healthy controls. In addition, the study reported gut microbiota is associated with abdominal pain in patients with IBS.


Assuntos
Síndrome do Intestino Irritável , Microbiota , Dor Abdominal/etiologia , Constipação Intestinal , Diarreia , Fezes , Hábitos , Humanos , Mucosa Intestinal/patologia , Prevotella , RNA Ribossômico 16S/genética
20.
Clin Res Hepatol Gastroenterol ; 46(6): 101969, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35659602

RESUMO

BACKGROUND AND AIMS: Endoscopic management is preferred to surgical management for large superficial colorectal lesions. However, the optimal endoscopic resection strategy (piecemeal endoscopic mucosal resection [pEMR] or endoscopic submucosal dissection [ESD]) is still debated from an economical point of view. To date, in France, there is no Health Insurance reimbursement rate for the hospital stays related to ESD. We searched to estimate the global cost of colorectal ESD and to define the most cost-effectiveness endoscopic strategy. METHODS: A model was created to compare the cost-effectiveness of ESD and pEMR according to optical diagnosis (Japan NBI Expert Team [JNET], laterally spreading tumour [LST], CONECCT). We distinguished three groups from the same multicentre ESD cohort and compared the medical and economic outcomes: real-life ESD data (Universal-ESD or U-ESD) compared to modelled selective ESD (S-ESD JNET; S-ESD LST; S-ESD CONECCT) and exclusive pEMR strategies (Universal-EMR or U-EMR). RESULTS: The en-bloc, R0, and curative resection rates were 97.5%, 86.5%, and 82.6%, respectively in the real life French ESD cohort of 833 colorectal lesions. U-ESD was the least-expensive strategy, with a global cost of 2,858,048.17 €, i.e. 3,431.03 €/patient and was also the most effective strategy because it avoided 774 surgeries, which was more than any other strategy. It outperformed S-ESD CONNECT (global cost = 2,951,411.44 €, and 3,543.11 €/patient, 765 surgeries avoided, S-ESD LST (global cost = 3,055,951.53 €, and 3,668.61 €/patient, 749 surgeries avoided), and S-ESD JNET (global cost = 3,547,426.97 € and 4,258.62 €/patient, 704 surgeries avoided) and U-EMR (global cost = 4,060,547.62 € and 4,874.61 €/patient, 620 surgeries avoided). Even though a model which optimized pEMR results (0% technical failure, 0% primary surgery), U-EMR strategy remained the most expansive strategy and the one that avoided the least surgeries. CONCLUSION: ESD for all LSTs upper than 20 mm is more cost-effective than pEMR, and S-ESD.


Assuntos
Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Colonoscopia/métodos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Análise Custo-Benefício , Ressecção Endoscópica de Mucosa/métodos , Humanos , Mucosa Intestinal/patologia , Estudos Retrospectivos , Resultado do Tratamento
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