Effect of probiotic therapy on periodontal tissues and intestinal mucosa of rats with ligature-induced periodontitis / Efeito da terapia probiótica nos tecidos periodontais e mucosa intestinal de ratos com periodontite induzida por ligadura

INTRODUCTION: As periodontitis is caused by dysbiotic biofilm, it is believed that therapy with probiotics can act to control the mechanisms of adhesion and colonization, competing with invading microorganisms. OBJECTIVE: Evaluate probiotic therapy effect on periodontal tissues and intestinal mucosa of rats with ligature-induced periodontitis. METHODS: 32 Wistar rats were divided into four groups (n=8): Control Group (CG); Periodontal disease (PD); Probiotic (PROB); PD + probiotic (PDPRO). PD and PDPRO received a ligature over the first lower molars and PROB and PDPRO the probiotic Lactobacillus acidophilus based were given orally for 44 days. The animals were euthanized and the blood was collected for evaluation of triglyceride and cholesterol concentrations. The hemimandibles were collected for histomorphometric and radiographic analysis. The duodenum was removed for morphological evaluation and gingival tissue around the molars was collected for analysis of IL-17. RESULTS: The ANOVA one-way test was used followed by Tukey Test. PDPRO had a significantly lower bone loss than the PD (p<0.05) and a smaller number of osteoclasts on PDPRO when compared to the PD. As for IL-17, there was a decrease in the PDPRO when compared to the PD. The histomorphometry of the duodenum showed that there was a significant increase in the width of the villi in PROB only. CONCLUSION: The therapy with probiotics was effective to avoid the development of periodontitis by reducing alveolar bone loss and inflammation modulation and increasing the width of the duodenum villi, which may help to restabilize the balance of the gastrointestinal tract.

INTRODUÇÃO: Como a periodontite é causada por biofilme disbiótico, acredita-se que a terapia com probióticos possa atuar no controle dos mecanismos de adesão e colonização, competindo com microrganismos invasores. OBJETIVO: Avaliar o efeito da terapia probiótica nos tecidos periodontais e mucosa intestinal de ratos com periodontite induzida por ligadura. MÉTODOS: 32 ratos Wistar foram divididos em quatro grupos (n=8): Grupo Controle (GC); Doença periodontal (PD); Probiótico (PROB); PD + probiótico (PDPRO). PD e PDPRO receberam ligadura sobre os primeiros molares inferiores e PROB e PDPRO, o probiótico à base de Lactobacillus acidophilus dado via oral por 44 dias. Os animais foram sacrificados e o sangue coletado para avaliação das concentrações de triglicerídeos e colesterol total. As hemimandíbulas foram coletadas para análise histomorfométrica e radiográfica. O duodeno foi removido para avaliação morfológica e o tecido gengival ao redor dos molares foi coletado para análise de IL-17. RESULTADOS: Foi usado Teste ANOVA seguido pelo Teste de Tukey. PDPRO teve uma perda óssea significativamente menor do que o PD (p<0.05) e um menor número de osteoclastos no PDPRO quando comparado ao PD. Já para IL-17, houve diminuição do PDPRO em relação ao PD. A histomorfometria do duodeno mostrou que houve aumento significativo da largura das vilosidades no PROB somente. CONCLUSÃO: A terapia com probiótico foi eficaz para evitar o desenvolvimento de periodontite por reduzir a perda óssea alveolar e a modulação da inflamação e aumentar a largura das vilosidades duodenais, o que pode ajudar a estabilizar o equilíbrio do trato gastrointestinal.

Campsiandra laurifolia reduces oxidative stress and Iiflammation in rats with ulcerative colitis

Ulcerative colitis (UC) affects the mucosa and submucosa of the large intestine. One of the mechanisms involved in its etiology is oxidative stress (OS), directly involved in the inflammatory process characteristic of UC. The Campsiandra laurifolia, known as acapurana, was described as possessing antioxidant properties. We used 24 male Wistar rats, divided into control (CO), control + acapurana (CO + A), colitis (CL), and colitis + acapurana (CL + A) groups. This study performed histological analysis, measuring anal sphincter pressure (ASP) and lipoperoxidation (LPO). The activity of the antioxidant enzyme superoxide dismutase (SOD) and glutathione (GSH) levels were evaluated. The expression of the nuclear factor kappa B (NFkB) and inducible nitric oxide synthase (iNOS) was analyzed by immunohistochemistry. The statistical analysis used was the one-way analysis of variance (ANOVA), followed by the Student-Newman-Keuls test; values were expressed as mean ± standard error, and the significance level was p < 0.05. In the animals of the CL group, we observed the destruction of the crypts and the presence of mucosal ulcers, edema, and submucosal inflammatory infiltrate, as well as increased damage to the intestinal mucosa, reduced ASP, increased LPO and SOD activity, reduced GSH levels, and increased expression of NFkB and iNOS. The administration of C. laurifolia in the CL + A group was shown to cause regeneration of crypts, reduction of inflammatory infiltrate, reduction of damage to the intestinal mucosa, increase in ASP, and reduction in LPO with the restoration of SOD activity and GSH levels. The immunohistochemistry of NFkB and iNOS was significantly reduced. Therefore, the C. laurifolia aqueous extract appears to exert an antioxidant and anti-inflammatory effect in rats with AA-induced colitis. (AU)

Changes in the structure of intestinal mucosal flora in colorectal cancer patients / 南方医科大学学报

OBJECTIVE@#To investigate the changes in bacterial flora in fecal samples, at the tumor loci and in adjacent mucosa in patients with colorectal cancer (CRC).@*METHODS@#We collected fecal samples from 13 patients with CRC and 20 healthy individuals and tumor and adjacent mucosa samples from 6 CRC patients. The differences in bacterial composition between the fecal and mucosa samples were analyzed with 16S rDNA sequencing and bioinformatics methods. We also detected the total number of bacteria in the feces using flow cytometry, isolated and identified the microorganisms in the fecal and mucosa samples using common bacterial culture media. We further tested the effects of 7 isolated bacterial strains on apoptosis of 3 CRC cell lines using lactate dehydrogenase detection kit.@*RESULTS@#The bacterial α-diversity in the feces of healthy individuals and in adjacent mucosa of CRC patients was significantly higher than that in the feces and tumor mucosa in CRC patients (P < 0.05). Lactobacillaceae is a specific bacteria in the feces, while Escherichia, Enterococcus, and Fusobacterium are specific bacteria in tumor mucosa of CRC patients as compared with healthy individuals. Cell experiment with3 CRC cell lines showed that Bacteroides fragilis isolated from the tumor mucosa of CRC patients produced significant inhibitory effects on cell proliferation (P < 0.0001), while the isolated strain Fusobacterium nucleatum obviously promoted the proliferation of the cell lines (P < 0.001).@*CONCLUSION@#The bacterial flora in the feces, tumor mucosa and adjacent mucosa of CRC patients is significantly different from that in the feces of healthy individuals, and the fecal flora of CRC patients can not represent the specific flora of the tumor mucosa. Inhibition of F. nucleatum colonization in the tumor mucosa and promoting B. fragilis colonization may prove beneficial for CRC treatment.

Avaliação de ressecção de mucosa endoscópica sob imersão d'água de pólipos colorretais em um centro ambulatorial no Brasil / Evaluation of underwater endoscopic mucosal resection for colorectal polyps in an outpatient clinic in brazil

ABSTRACT BACKGROUND: Since 2012, a new technique for resection of large polyps has been described, the underwater endoscopic mucosal resection (UEMR). Some advantages that emerge from it is the needless of injection in submucosal layer and a greater chance of complete capture of the polyp. OBJECTIVE: There are few studies of UEMR in Brazil. The aim of this study is to evaluate the safety and efficacy of this technique in one Brazilian center. METHODS: This case series was conducted from February to December of 2020. Colorectal polyps greater than 9 mm without features of deep submucosal invasion were resected using UEMR. RESULTS: Twenty-four large polyps were resected with the UEMR approach from 24 patients. The mean size of the polys was 19 mm, ranging from 12 to 35 mm. All lesions were successful resected and 66% (16/24) were resected en bloc. In histologic analyses, most of them were adenomas (70.8%) and only one had deep submucosal invasion. There were no cases of acute complications, such perforation or acute bleeding. CONCLUSION: The UEMR is a safe and feasible procedure. With the emerging data on the procedure, it seems to be a wonderful tool in preventing colorectal cancer and its applicability and scope should be encourage to surpass reference centers.

RESUMO CONTEXTO: Desde 2012, uma nova técnica para ressecção de pólipos grandes tem sido descrita, a ressecção da mucosa endoscópica sob imersão d'água (REMS). Algumas vantagens que surgem desta técnica são evitar a injeção na camada submucosa e a maior chance de captura completa do pólipo. Objetivo - Há poucos estudos com REMS no Brasil. Nosso objetivo é avaliar a segurança e a eficácia da técnica em um centro brasileiro. MÉTODOS: Esta série de casos foi conduzida de fevereiro a dezembro de 2020. Pólipos colorretais maiores que 9 mm sem sinais endoscópicos de invasão de submucosa foram ressecados utilizando RMES. RESULTADOS: Vinte e quatro pólipos foram ressecados com RMES em 24 pacientes diferentes. O tamanho médio dos pólipos era de 19 mm, variando de 12 a 35 mm. Todas as lesões foram ressecadas e 66% (16/24) foram ressecadas em monobloco. Na análise histológica, a maioria era adenoma (70.8%) e apenas uma havia invasão profunda da submucosa. CONCLUSÃO: O uso de REMS é um procedimento seguro e factível. Com o aumento de dados relativos ao procedimento, esta parece ser uma excelente ferramenta na prevenção do câncer colorretal e sua aplicabilidade deve ser encorajada para fora dos centros de referência.

Ressecção endoscópica sob imersão d'água de pequenos tumores neuroendócrinos retais / Underwater endoscopic mucosal resection for small rectal neuroendocrine tumors

ABSTRACT BACKGROUND: A common site of neuroendocrine tumors (NETs) is the rectum. The technique most often used is endoscopic mucosal resection with saline injection. However, deep margins are often difficult to obtain because submucosal invasion is common. Underwater endoscopic mucosal resection (UEMR) is a technique in which the bowel lumen is filled with water rather than air, precluding the need for submucosal lifting. OBJECTIVE: This study aimed to evaluate the efficacy and safety of UEMR for removing small rectal neuroendocrine tumors (rNETs). METHODS: Retrospective study with patients who underwent UEMR in two centers. UEMR was performed using a standard colonoscope. No submucosal injection was performed. Board-certified pathologists conducted histopathologic assessment. RESULTS: UEMR for small rNET was performed on 11 patients (nine female) with a mean age of 55.8 years and 11 lesions (mean size 7 mm, range 3-12 mm). There were 9 (81%) patients with G1 rNET and two patients with G2, and all tumors invaded the submucosa with only one restricted to the mucosa. None case showed vascular or perineural invasion. All lesions were removed en bloc. Nine (81%) resections had free margins. Two patients had deep margin involvement; one had negative biopsies via endoscopic surveillance, and the other was lost to follow-up. No perforations or delayed bleeding occurred. CONCLUSION: UEMR appeared to be an effective and safe alternative for treatment of small rNETs without adverse events and with high en bloc and R0 resection rates. Further prospective studies are needed to compare available endoscopic interventions and to elucidate the most appropriate endoscopic technique for resection of rNETs.

RESUMO CONTEXTO: Um local comum de tumores neuroendócrinos (TNEs) é o reto. A técnica mais utilizada é a ressecção endoscópica da mucosa com injeção de solução salina. No entanto, as margens profundas costumam ser difíceis de ressecar porque a invasão da submucosa é comum. A ressecção endoscópica sob imersão d'água (RESI) é uma técnica em que o lúmen intestinal é preenchido com água em vez de ar, evitando a necessidade de elevação submucosa. OBJETIVO: Este estudo teve como objetivo avaliar a eficácia e segurança da RESI para a remoção de pequenos TNEs retais (rTNEs). MÉTODOS: Estudo retrospectivo com pacientes que realizaram RESI em dois centros. RESI foi realizada usando um colonoscópio padrão. Nenhuma injeção submucosa foi realizada. Patologistas certificados conduziram avaliação histopatológica. RESULTADOS: RESI foi realizada para pequenos rTNEs em 11 pacientes (nove mulheres) com média de idade de 55,8 anos e 11 lesões (tamanho médio de 7 mm, variando de 3-12 mm). Havia 9 (81%) pacientes com G1 rTNEs e dois pacientes com G2, sendo que todos os tumores invadiam a submucosa sendo apenas um restrito a mucosa. Nenhum caso mostrou invasão vascular ou perineural. Todas as lesões foram removidas em bloco. Nove (81%) ressecções tiveram margens livres. Dois pacientes tiveram envolvimento de margens profundas; um teve biópsias negativas por meio de vigilância endoscópica e o outro perdeu o acompanhamento. Não ocorreram perfurações ou sangramento tardios. CONCLUSÃO: A RESI parece ser uma alternativa eficaz e segura para o tratamento de pequenos rTNEs sem eventos adversos e com altas taxas de ressecção em bloco e R0. Mais estudos prospectivos são necessários para comparar as intervenções endoscópicas disponíveis e para elucidar a técnica endoscópica mais adequada para ressecção de rTNEs.

Sucralfate enemas reduce the oxidative tissue damage and preserves the contents of E-cadherin and Β-catenin in colonic mucosa without fecal stream

ABSTRACT Purpose: To evaluate the effects of sucralfate enemas in tissue contents of E-cadherin and ?-catenin in an experimental diversion colitis. Methods: Thirty-six male Wistar rats were submitted to a proximal colostomy and a distal mucous fistula. They were allocated into three groups: first group received daily saline enemas (2 mL/day) and the two other groups daily enemas with sucralfate at dosage of 1 or 2 g/kg/day, respectively. Six animals of each group were euthanized after two weeks and six animals after four weeks. The inflammation of the excluded mucosa was evaluated by histological analysis. The oxidative damage was quantified by measurement of malondialdehyde tissue levels. The expression of E-cadherin and ?-catenin was identified by immunohistochemistry, and its contents were quantified by computer-assisted image analysis. Results: Sucralfate enemas reduced inflammation in animals subjected to treatment with 2 g/kg/day by four weeks, and the levels of oxidative damage in mucosa without fecal stream irrespective of concentration and time of intervention. E-cadherin and ?-catenin content increased in segments without fecal stream in those animals subjected to treatment with sucralfate. Conclusions: Sucralfate reduces the inflammation and oxidative stress and increases the tissue content of E-cadherin and ?-catenin in colonic mucosa devoid to the fecal stream.

Establishment of mini-guts organoid and research on intestinal disease from the new perspective / 中华胃肠外科杂志

Intestinal organoids, also named "mini-guts", reconstitute sophisticated three-dimensional architecture recapitulating diversified intestinal epithelial cell types and physiology, which is driven by the proliferative and self-assembling characteristics of crypt stem cells. The initiation of organoids study relies on the identification of Lgr5+ crypt stem cells from different intestinal segments and the key role of EGF, Wnt, BMP/TGF-β, Notch signal pathways within the microenvironment during the cultivation process. Besides constituting polarized crypt-villus structures, these "mini-guts" exhibit various effective functions of intestinal epithelium. Since 2009 when the culture system of small intestinal organoids was established by Sato et al, intestinal organoids excel conventional intestinal models depending on genetical mutation in multiple aspects and thus have become the hotspot among the research on intestinal diseases. Combined with genomics, material science and engineering, "mini-guts" have been widely applied to the research on intestinal development, intestinal transport physiology, epithelial barrier, pathogen-host interaction and the study on cystic fibrosis, infectious diarrhea, ulcerative colitis, Crohn's disease, intestinal cancer, etc. In this review, we summarize the new insights introduced by organoid into the research on intestinal diseases, and related research advances and applications.

Effect of acupoint thread-embedding on tight junction of intestinal mucosa epithelium in rats with ulcerative colitis / 中国针灸

OBJECTIVE@#To observe the effect of acupoint thread-embedding on tight junction of intestinal mucosal epithelial barrier in rats with ulcerative colitis (UC) under the state of "deficiency and stasis", and to explore its mechanism.@*METHODS@#Sixty male SD rats were randomly divided into a control group (@*RESULTS@#Compared with the control group, in the model group the body weight was decreased (@*CONCLUSION@#The thread-embedding could repair the tight junction of intestinal mucosa epithelium and reduce the permeability of intestinal mucosa epithelium, which may be related to the decrease of the expression of CaMKⅡ, MLCK and other protein kinases.

Association of colonoscopy and histopathological findings of the canine large intestine and ileum abnormalities: 54 cases series / Associação de achados de colonoscopia e histopatologia do intestino grosso e íleo de cães: série de 54 casos

Colonoscopy is a minimally invasive technique used to assess the large intestine through direct inspection of the intestinal mucosa. When associated with histopathological examination of fragments collected from the intestine, the definitive diagnosis can be obtained. This retrospective study evaluated colonoscopy and histopathological exams of the large intestine and ileum of dogs with gastrointestinal disorders admitted at the Veterinary Hospital of the Federal University of Minas Gerais (UFMG) and the Veterinary Hospital São Francisco de Assis to determine the frequency of injuries, their distribution in the intestinal segments, and the relationship of the findings observed in these two analyzes. The colonoscopy and histopathological findings of the case series were described using absolute and relative frequencies, as well as nature and intensity classification of the findings. Cohen's Kappa coefficient was obtained to assess the concordance of nature and intensity classifications between colonoscopy and histopathology, and its 95% confidence interval constructed. The analyses were performed using the Software SAS University Edition. It was observed a moderate agreement between the classification of the nature of the findings by endoscopy and histopathology (Kappa coefficient = 0.39, CI = 0.20-0.59). This can also be observed when assessing the frequency of similar diagnoses between the methods, since only 39 (72.22%) were consistent, i.e., 15 (22.78%) diagnoses differed depending on the nature of the finding, which could have a great influence on the final diagnosis if histopathology was disregarded. For the intensity of the injuries, little agreement was observed between the methods (Kappa coefficient = 0.1243, C = -0.05-0.30). This was even more evident in the frequency of similar diagnoses in terms of intensity, of which 20 (37.04%) were similar and 34 (62.96%) were different. Inflammatory affections are the most frequently observed alterations in the large intestine and ileum of dogs. The most common finding that reveals inflammatory changes is the lymphoplasmacytic infiltrate. As for the proliferative and neoplastic lesions, adenomatous polyps and lymphoma were common. The most affected sites of the large intestine were the descending colon and the rectum. Findings such as edema and reddening of the mucosa were frequent by macroscopy. Although the changes observed by colonoscopy and histopathology may not be similar, these techniques are complementary, which makes biopsies mandatory for a diagnostic conclusion.(AU)

A colonoscopia é uma técnica pouco invasiva utilizada para avaliação do intestino grosso por meio de inspeção direta da mucosa intestinal. Quando associada ao exame histopatológico, com a coleta de fragmentos do intestino, o diagnóstico definitivo pode ser obtido. O objetivo desse estudo retrospectivo foi associar os achados de exames de colonoscopia e histopatologia do intestino grosso e íleo em 54 cães com distúrbios gastrointestinais dos Hospitais Veterinários da Universidade Federal de Minas Gerais (UFMG) e São Francisco de Assis. Na colonoscopia, as alterações mais frequentemente observadas foram edema, friabilidade e avermelhamento de mucosa. Quanto à distribuição de lesões por segmento intestinal, houve maior incidência de alterações inflamatórias, das quais foram as mais frequentes, com o infiltrado linfoplasmocitário sendo o mais comum em todos segmentos analisados (i.e. reto, cólon, ceco e íleo). O cólon ascendente e o reto foram os locais de alterações mais frequentes na colonoscopia e na histopatologia. Os pólipos hiperplásicos e o linfoma foram as lesões proliferativas de ocorrência mais comum. Houve baixa concordância entre as classificações por natureza e intensidade dos achados na colonoscopia e histopatologia. Assim, não foi possível associar alterações descritas nos exames histopatológicos quanto à natureza e intensidade das lesões utilizando a colonoscopia, o que leva à conclusão de que é essencial a realização de biópsias em todos os exames para conclusão diagnóstica.(AU)

Jiawei Baitouweng Decoction affects intestinal mucosal tight junction proteins in rats with ulcerative colitis through p38 MAPK-MLCK signaling pathway / 中国中药杂志

The aim of this paper was to explore the effect and mechanism of Jiawei Baitouweng Decoction(JWBTW) against ulcerative colitis(UC) from the perspective of intestinal mucosal tight junction proteins. From 60 SPF-grade male SD rats, 10 were randomly selected as the blank control, and the remaining 50 were treated with 3% dextran sodium sulfate(DSS) solution to induce UC and then randomized into the model group, mesalazine group, and low-, medium-, and high-dose JWBTW( L-JWBTW, M-JWBTW and H-JWBTW) groups, with 10 rats in each group. After successive medication for 14 days, the rat general conditions like body weight and stool were observed and the disease activity index(DAI) was calculated. The pathological changes in colon tissue was observed under a microscope for injury severity scoring and histopathological scoring. The serum endotoxin content was determined by limulus assay, followed by the measurement of protein expression levels of ZO-1, occludin, claudin-1, p38 MAPK, MLCK, MLC2 and p-MLC in colon tissue by Western blot. The results showed that compared with the blank group, the model group exhibited significantly reduced body weight, elevated DAI, injury severity and histopathological scores and serum endotoxin content, up-regulated protein expression levels of p38 MAPK, MLCK, MLC2 and p-MLC, and down-regulated ZO-1, occludin and claudin-1. Compared with the model group,mesalazine and JWBTW at each dose obviously increased the body weight, lowered the DAI, injury severity and histopathological scores and serum endotoxin content, down-regulated the protein expression levels of p38 MAPK, MLCK, MLC2 and p-MLC, and up-regulated the ZO-1, occludin and claudin-1, with the most obvious changes noticed in the H-JWBTW group. All these have indicated that JWBTW exerts the therapeutic effect against UC by inhibiting the activation of p38 MAPK/MLCK pathway, reversing the protein expression levels of occludin, claudin-1 and ZO-1, decreasing the serum endotoxin content, promoting the repair of intestinal mucosal mechanical barrier, maintaining the integrity of tight junctions, and reducing the permeability of intestinal mucosa.

Effect of moxibustion on colonic mucosal injury and expression of CGRP positive nerve fibers of distal colonic mucosa in ulcerative colitis mice / 中国针灸

OBJECTIVE@#To observe the effect of moxibustion at "Zusanli" (ST 36) on distal, middle and proximal colonic mucosal injury and expression of calcitonin gene-related peptide (CGRP) positive nerve fibers of distal colonic mucosa in ulcerative colitis (UC) mice at different time points.@*METHODS@#A total of 51 C57BL/6N mice were randomized into a 7-day control group (@*RESULTS@#Mucosal injury can be observed in mice after modeling, displaying epithelial layer disappearance, abnormal crypt structure or crypt disappearance. Compared with the 7-day control group, colon length was shortened (@*CONCLUSION@#Moxibustion at "Zusanli" (ST 36) can reduce the expressions of positive nerve fibers of colonic mucosa and CGRP positive nerve fibers of distal colonic mucosa, thus, improve the colonic mucosal injury.

Protective effects of Dendrobium officinale superfine powder against LPS-induced intestinal mucosal injury in mice / 中国中药杂志

This study aims to investigate the preventive effect of Dendrobium officinale in LPS-induced intestinal mucosal damage. Forty SPF-grade C57 BL/6 J male mice were randomly divided into normal group(NC), model group(LPS), and two superfine powder groups of Dendrobium officinale(DOF)(DOF-L, 0.30 g·kg~(-1)and DOF-H, 0.60 g·kg~(-1), respectively), with 10 mice in each group. DOF superfine powder suspension was given via oral administration to mice for 7 days, while the mice in NC and LPS groups received the same volume of saline for 7 days. On the eighth day, the mice in LPS group and DOF treatment groups were injected with LPS(5 mg·kg~(-1)) by intraperitoneal injection to establish the intestinal mucosal injury model, while the mice in NC group were injected with the same volume of sterile saline in the same manner. Six hours after injection with LPS or saline, plasma and the intestinal tissue were collected. The diamine oxidase(DAO) and D-lactate levels in plasma were detected with a biochemical method. The levels of proinflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in plasma were detected by ELISA. The histomorphology and ultrastructure of mouse ileum tissues were observed by hematoxylin-eosin(HE) staining in optical microscope and transmission electron microscope(TEM). The expression and distribution of tight junction(TJ) proteins claudin-1, occludin and F4/80 were detected by immunohistochemistry while the protein expression levels of Toll-like receptor 4(TLR-4) and nuclear factor kappa B p65(NF-κB p65) in jejunum were detected by Western blot. The experimental results showed that continuous intragastric administration of D. officinale superfine powder for 7 days obviously alleviated the damage and ultrastructural changes of intestinal mucosa induced by LPS; significantly decreased DAO and D-lactate levels in plasma in model group(P<0.05); up-regulated the protein expression of claudin-1 and occludin in ileum tissues; down-regulated the protein expression of TLR-4 and NF-κB p65 in jejunum tissues(P<0.01); significantly decreased TNF-α and IL-6 levels in plasma(P<0.05); and decreased the infiltration of F4/80~+ macrophage cells. Our results suggested that D. officinale had significant protective effects on LPS-induced intestinal mucosal damage and reduced intestinal permeability. The mechanism might be related to its effects of inhibiting inflammation via TLR-4/NF-κB p65, and up-regulating the expression of tight junction proteins.

Research progress of effect of berberine in treatment of ulcerative colitis based on cell signaling pathway / 中国中药杂志

Berberine is the main extract of Coptis chinensis, and its anti-inflammatory, antioxidant, antibacterial and immunomodulatory effects have been confirmed by modern studies. Ulcerative colitis(UC) is a chronic, idiopathic inflammatory bowel disease with unknown etiology. Its causes involve genetics, intestinal microecology and mucosal immune system disorders. In this paper, literatures on relevant pathways and mechanism of berberine on ulcerative colitis in recent years were consulted and summarized to provide me-thods and ideas for developing berberine in the treatment of UC and exploring the mechanisms. The results showed that berberine protects the intestinal mucosal barrier, restores the body's normal immune response, and improves oxidative stress by regulating multiple signaling pathways, such as JAK-STAT, NK-κB, PI3 K-AKT, MAPK, Nrf2, ERS, and MLCK-MLC, so as to treat UC.

Curcumin mediates IL-6/STAT3 signaling pathway to repair intestinal mucosal injury induced by 5-FU chemotherapy for colon cancer / 中国中药杂志

This study aims to investigate the potential mechanism of curcumin in mediating interleukin-6(IL-6)/signal transducer and activator of transcription 3(STAT3) signaling pathway to repair intestinal mucosal injury induced by 5-fluorouracil(5-FU) chemotherapy for colon cancer. SD rats were intraperitoneally injected with 60 mg·kg~(-1)·d~(-1) 5-FU for 4 days to establish a model of intestinal mucosal injury. Then the rats were randomly divided into model group(equal volume of normal saline), curcumin low, medium and high dose groups(50, 100, 200 mg·kg~(-1)), and normal SD rats were used as control group(equal volume of normal saline). Each group received gavage administration for 4 consecutive days, and the changes of body weight and feces were recorded every day. After administration, blood was collected from the heart, and jejunum tissues were collected. The levels of serum interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) were detected by ELISA, and at the same time, the concentration of Evans blue(EB) in jejunum was measured. Hematoxylin-eosin(HE) staining was used to observe the pathological state of jejunum, and the length of jejunum villi and the depth of crypt were measured. The positive expression levels of claudin, occludin and ZO-1 were detected by immunohistochemistry. Western blot was used to detect the protein expression of IL-6, p-STAT3, E-cadherin, vimentin and N-cadherin in jejunum tissues. The results showed that, curcumin significantly increased body weight and fecal weight(P<0.05 or P<0.01), decreased fecal score, EB concentration, IL-1β and TNF-α levels(P<0.05 or P<0.01) in rats. In addition, curcumin maintained the integrity of mucosal surface and villi structure of jejunum to a large extent, and reduced pathological changes in a dose-dependent manner. Meanwhile, curcumin could increase the positive expression of occludin, claudin and ZO-1(P<0.05 or P<0.01), repair intestinal barrier function, downregulate the protein expression of IL-6, p-STAT3, vimentin and N-cadherin in jejunum tissues(P<0.05 or P<0.01), and upregulate the protein expression of E-cadherin(P<0.05). Therefore, curcumin could repair the intestinal mucosal injury induced by 5-FU chemotherapy for colon cancer, and the mechanism may be related to the inhibition of IL-6/STAT3 signal and the inhibition of epithelial-mesenchymal transition(EMT) process.

Tissue content of metalloproteinase-9 and collagen in the colon with and without fecal stream after intervention with infliximab in rats subjected to Hartmann's surgery

ABSTRACT Purpose Quantify the tissue content of metalloproteinase-9 (MMP-9) and collagen in colic mucosa with and without intestinal transit after infliximab administration in rats subjected to Hartmann's surgery. Methods Twenty-two rats underwent colon diversion by Hartmann's surgery. Animals were maintained with intestinal bypass for 12 weeks to induce development of diversion colitis (DC). Afterwards, animals were divided into three groups: first group received subcutaneous application of saline solution (SS) 0.9%, while the remaining two groups received infliximab subcutaneously at doses of 5 or 10 mg·kg-1·week-1 for five consecutive weeks. After the intervention, animals were sacrificed, removing the segments with and without intestinal transit. Diversion colitis was diagnosed by histological study, and its intensity was determined by a validated inflammatory scale. Tissue expression of MMP-9 was assessed byimmunohistochemistry, while total collagen was assessed by histochemistry. Tissue content of both was measuredby computerized morphometry. Results Colon segments without intestinal transit had a higher degree of inflammation, which improved in animals treated with infliximab. Collagen content was always lower in those without intestinal transit. There was an increase in the collagen content in the colon without transit in animals treated with infliximab, primarily at a dose of 10 mg·kg-1·week-1. There was an increase in the content of MMP-9 in the colon without fecal transit, and a reduction was observed in animals treated with infliximab, regardless of the dose used. Conclusions Application of infliximab reduces inflammation, increases the total collagen content and decreases the content of MMP-9 in the colon without intestinal transit.

Ressecção da mucosa endoscópica sob imersão dágua para lesões colorretais não pediculadas. Um estudo prospectivo de braço único / Underwater endoscopic mucosal resection for non-pedunculated colorectal lesions. a prospective single-arm study

ABSTRACT BACKGROUND: Underwater endoscopic mucosal resection (UEMR) has emerged as a revolutionary method allowing resection of colorectal lesions without submucosal injection. Brazilian literature about this technique is sparse. OBJECTIVE: The aim of this study was evaluate the efficacy and safety of UEMR technique for removing non-pedunculated colorectal lesions in two Brazilian tertiary centers. METHODS: This prospective study was conducted between June 2016 and May 2017. Naïve and non-pedunculated lesions without signs of submucosal invasion were resected using UEMR technique. RESULTS: A total of 55 patients with 65 lesions were included. All lesions, except one, were successfully and completely removed by UEMR (success rate 98.5%). During UEMR, two cases of bleeding were observed (3.0%). One patient had abdominal pain on the day after resection without pneumoperitoneum. There was no perforation or delayed bleeding. CONCLUSION: This study supports the existing data indicating acceptable rates of technical success, and low incidence of adverse events with UEMR. The results of this Brazilian study were consistent with previous abroad studies.

RESUMO CONTEXTO: A ressecção endoscópica da mucosa sob imersão d'água (REMS) surgiu como um método revolucionário que permite a ressecção de lesões colorretais sem injeção submucosa. A literatura brasileira sobre essa técnica é escassa. OBJETIVO: A finalidade deste estudo foi avaliar a eficácia e segurança da técnica REMS na remoção de lesões colorretais não pediculadas em dois centros terciários brasileiros. MÉTODOS: Este estudo prospectivo foi realizado entre junho de 2016 e maio de 2017. As lesões sem tentativa de ressecção prévia, não pediculadas e sem sinais de invasão submucosa foram ressecadas pela técnica REMS. RESULTADOS: Um total de 55 pacientes com 65 lesões foram incluídos. Todas as lesões, exceto uma, foram removidas com sucesso e completamente por REMS (taxa de sucesso de 98,5%). Durante a REMS, foram observados dois casos de sangramento (3,0%). Uma paciente apresentou dor abdominal no dia seguinte à ressecção sem pneumoperitônio. Não houve perfuração ou sangramento tardio. CONCLUSÃO: Este estudo apoia os dados existentes, indicando taxas aceitáveis de sucesso técnico e baixa incidência de eventos adversos com a REMS. Os resultados deste estudo brasileiro foram consistentes com estudos internacionais prévios.

Effects of Huoxiang Zhengqi Oral Liquid on intestinal barrier function in rats with dampness obstructing spleen-stomach syndrome / 中国中药杂志

The aim of this paper was to investigate the effect of Huoxiang Zhengqi Oral Liquid on intestinal barrier functions in rats with dampness obstructing spleen-stomach syndrome and primarily explore the mechanism. The rat model of dampness obstructing spleen-stomach syndrome was established, and then the modeled rats were randomly divided into the model control group, Huoxiang Zhengqi Oral Liquid high and low dose groups, and natural recovery group according to gender and body weight, with 10 rats in each group. Another 10 rats were taken as blank control group. After each group received the corresponding treatment for 7 days, rat serum was isolated. D-lactic acid content was detected by the MTT method, and diamine oxidase(DAO) activity was detected by the rate method. Colon tissues of the rats were isolated to detect Na~+-K~+-ATPase activity and Ca~(2+)-Mg~(2+)-ATPase activity by phosphate determination method, glutathione peroxidase(GSH-Px) activity was detected by spectrophotometry, catalase(CAT) activity was detected by ammonium molybdate, superoxide dismutase(SOD) activity was detected by hydroxylamine, the expression of occludin protein and ZO-1 protein was detected by immunofluorescence, and the expression levels of occludin protein and ZO-1 protein were detected by Western blot. RESULTS:: showed that low dose Huoxiang Zhengqi Oral Liquid could improve the body weight, diet, stool and urine state of rats with dampness obstructing spleen-stomach syndrome obviously. The D-lactic acid content and the DAO activity in the serum of rats with dampness obstructing spleen-stomach syndrome were reduced obviously. The activities of Na~+-K~+-ATPase, Ca~(2+)-Mg~(2+)-ATPase, GSH-Px, CAT and SOD in rat colon tissues were increased obviously. The occludin proteins and ZO-1 protein expression levels in rat colon tissues were raised obviously. The differences in the above indexes between Huoxiang Zhengqi Oral Liquid group and the model control group were statistically significant(P<0.05). Huoxiang Zhengqi Oral Liquid could effectively restore the intestinal barrier function in rats with dampness obstructing spleen-stomach syndrome and its mechanism may be related to the repair of intestinal mechanical barrier function.

Effect of Schizonepetae Herba and Saposhnikoviae Radix on expression of AQP4 and AQP8 in colonic mucosa of rats with ulcerative colitis / 中国中药杂志

The aim of this paper was to investigate the effect of Schizonepetae Herba and Saposhnikoviae Radix(wind medicine) on the expression of AQP4 and AQP8 in colonic mucosa in rats with ulcerative colitis(UC). A total of 35 healthy SD male rats were randomly divided into normal group(gavaged with normal saline), DSS model group, as well as low, middle, and high dose wind medicine groups(Schizonepeta and Saposhnikovia 1∶1, gavaged at dosages of 6, 12, and 24 g·kg~(-1)·d~(-1)), with 7 in each group. UC rat model was established by free drinking of 3% dextran sulphate sodium(DSS) solution for 10 days. At the end of the 10 th day after the treatment, mice were put to death to collect colonic mucosa. The length of colon was measured; the colonic mucosal injury index(CMDI) and pathological changes of colon were observed. ELISA method was used for measuring the content of serum IL-1, IL-8, and immunohistochemical method was used to measure AQP4, AQP8 protein expressions in colon mucosa. The expressions of AQP4, AQP8 mRNA were measured by Real-time PCR. As compared with the normal group, the length of colon tissue was significantly reduced(P<0.01), CMDI scores and pathological scores were significantly increased(P<0.01), the levels of serum IL-1 and IL-8 were significantly increased(P<0.05) in model group; the immunohistochemical results showed that the protein expressions of AQP4, AQP8 were lower; the color was light yellow or brown; AQP4, AQP8 mRNA expressions in colon mucosa were significantly decreased in model group(P<0.01). CMDI scores, pathological scores, and the levels of serum IL-1, IL-8 in high, middle, low dose wind medicine groups were obvious lower than those in the model group(P<0.01 or P<0.05); the protein expressions of AQP4, AQP8 were higher; the color was chocolate brown or dark brown; the length of colon tissue, and the expressions of AQP4, AQP8 mRNA were obvious higher in wind medicine groups(P<0.01 or P<0.05). Schizonepetae Herba and Saposhnikoviae Radix could significantly improve the symptoms and histopathology of UC model rats and accelerate the intestinal mucosal healing. The mechanism may be related with up-regulating the expression level of AQP4 and AQP8 in colonic mucosa.

Cell death of intestinal epithelial cells in intestinal diseases / 生理学报

Gut injury continues to be the devastating and unpredictable critical illness associated with increased cell death of intestinal epithelial cells (IECs). The IECs, immune system and microbiome are the interrelated entities to maintain normal intestinal homeostasis and barrier integrity. In response to microbial invasion, IEC cell death occurs to maintain intestinal epithelium function and retain the continuous renewal and tissue homeostasis. But the imbalance of IEC cell death results in increased intestinal permeability and barrier dysfunction that leads to several acute and chronic intestinal diseases, such as intestinal ischemia/reperfusion (I/R), sepsis, inflammatory bowel diseases (IBD), necrotizing enterocolitis (NEC), etc. During the pathophysiological state, the excessive IEC apoptotic cell death leads to a chronic inflammatory condition, later switches to necroptotic cell death mechanism that induces more pathological features than apoptosis and may also induce other lytic cell death mechanisms like pyroptosis and ferroptosis to increase the pathogenesis of the intestinal diseases. But still, there remains gaps in the fundamental knowledge about the IEC cell death mechanisms in chronic intestinal diseases. Together, a deep understanding of the specific cell death mechanisms underlying chronic intestinal diseases, including sepsis, IBD, NEC, and intestinal I/R, is desperately needed to develop emerging novel promising therapeutic strategies. This review aims to show how the acute and critical illness in the gut are driven by IEC cell death mechanism, such as apoptosis, necrosis, necroptosis, pyroptosis, and ferroptosis.

Posttranscriptional control of intestinal epithelium homeostasis by RNA-binding protein HuR / 生理学报

The mammalian intestinal epithelium is a rapidly self-renewing tissue in the body and directly interfaces with a wide array of luminal noxious contents and microorganisms. Homeostasis of the intestinal epithelium is preserved through well-controlled mechanisms including posttranscriptional regulation. RNA-binding protein (RBP) HuR regulates the stability and translation of target mRNAs and is intimately involved in many aspects of gut mucosal pathophysiology. Here we highlight the biological roles of HuR in maintaining the integrity of the intestinal epithelium, with particular focus on the emerging evidence of HuR in the regulation of intestinal epithelial renewal, mucosal repair, defense, and gut permeability. We also further analyze the mechanisms through which HuR and its interactions with other RBPs and noncoding RNAs (ncRNAs) such as microRNAs and long ncRNAs modulate the intestinal epithelial homeostasis. With rapidly advancing knowledge of RBPs and ncRNAs, there is growing recognition that posttranscriptional control of the intestinal epithelium homeostasis might be promising therapeutic targets in our efforts to protect the integrity of the intestinal epithelium under critical pathological conditions.