Effects Comparison between Endoscopic Papillary Large Balloon Dilatation and Endoscopic Sphincterotomy for Common Bile Duct Stone Removal

Endoscopic sphincterotomy (EST) is a treatment of choice for stone extraction and is now most frequently used. The study was to compare the efficacy of endoscopic papillary large balloon dilatation (EPLBD) and endoscopic sphincterotomy (EST) for common bile duct stone removal. Trials comparing the effects between EPLBD and EST treatment were searched according to the study protocol. Overall stone removal rate, complete removal rate in 1st session, treatment duration, mechanical lithotripsy using rate, and overall complication rate were compared using risk ratio (RR) and mean difference (MD) and their 95% confidence interval (CI) via RevMan 5.2 software. For overall stone removal rate, two therapies showed similar effect, but EPLBD showed better overall stone removal rate for stone >10 mm in diameter. For complete stone removal rate in 1st session, no difference was found, even for those with stone >10 mm in diameter; EPLBD showed longer treatment duration, higher mechanical lithotripsy using rate obvious overall complications rate, and more serious bleeding, whereas there were no significant differences for perforation, hyperamylasemia, pancreatitis, and cholecystitis/cholangitis. EPLBD showed better efficacy in certain conditions compared to EST, however with shortcomings, such as more duration, higher mechanical lithotripsy using rate, more serious overall complications rate, and bleeding

Bacteroides fragilis Prevents Clostridium difficile Infection in a Mouse Model by Restoring Gut Barrier and Microbiome Regulation

Clostridium difficile is currently the leading cause of nosocomial infection. Antibiotics remain the first-line therapy for C. difficile-associated diseases (CDAD), despite the risks of resistance promotion and further gut microbiota perturbation. Notably, the abundance of Bacteroides fragilis was reported to be significantly decreased in CDAD patients. This study aimed to clarify the prophylactic effects of B. fragilis strain ZY-312 in a mouse model of C. difficile infection (CDI). The CDI mouse model was successfully created using C. difficile strain VPI 10463 spores, as confirmed by lethal diarrhea (12.5% survival rate), serious gut barrier disruption, and microbiota disruption. CDI model mice prophylactically treated with B. fragilis exhibited significantly higher survival rates (100% in low dosage group, 87.5% in high dosage group) and improved clinical manifestations. Histopathological analysis of colon and cecum tissue samples revealed an intact gut barrier with strong ZO-1 and Muc-2 expression. The bacterial diversity and relative abundance of gut microbiota were significantly improved. Interestingly, the relative abundance of Akkermansia muciniphila was positively correlated with B. fragilis treatment. In vitro experiments showed that B. fragilis inhibited C. difficile adherence, and attenuated the decrease in CDI-induced transepithelial electrical resistance, ZO-1 and MUC-2 loss, and apoptosis, suggesting that B. fragilis protected against CDI possibly by resisting pathogen colonization and improving gut barrier integrity and functions. In summary, B. fragilis exerted protective effects on a CDI mouse model by modulating gut microbiota and alleviating barrier destruction, thereby relieving epithelial stress and pathogenic colitis triggered by C. difficile. This study provides an alternative preventative measure for CDI and lays the foundations for further investigations of the relationships among opportunistic pathogens, commensal microbiota, and the gut barrier

MiR-218 regulates epithelial–mesenchymal transition and angiogenesis in colorectal cancer via targeting CTGF

Abstract Background Endothelial-to-mesenchymal transition (EMT) and angiogenesis play important roles in colorectal cancer (CRC) development. Connective tissue growth factor (CTGF) has been reported to promote several kinds of cancer progression and miR-218 has been identified as a tumor suppressor miRNA. However, little is known about the function of miR-218 in CRC. Here we investigated the effects of miR-218 on EMT and angiogenesis process in CRC cells. As well, the relation between miR-218 and CTGF was identified. The mechanism of miR-218’s function was illustrated. Methods CRC cell lines were transfected with miR-218 mimics. Proliferation, migration and angiogenesis were identified by MTT assay, Transwell assay, colony formation assay and tube formation assay. Protein and mRNA expression levels of associated genes were measured by Western blotting and RT-PCR. Dual luciferase assay was used to determine the relation of miR-218 and CTGF. Results miR-218 was down-regulated in CRC cell lines and over expression of miR-218 could significantly inhibit EMT and angiogenesis. CTGF was a direct target of miR-218. Up regulation of CTGF level after miR-218 transfection could sufficiently rescue the suppression effects on EMT and angiogenesis. Conclusion miR-218 directly targets CTGF and inhibits its expression, leading to suppression on EMT and angiogenesis of CRC cells. miR-218 might be used as potential therapeutic strategy for CRC treatment

Allicin Alleviates Inflammation of Trinitrobenzenesulfonic Acid-Induced Rats and Suppresses P38 and JNK Pathways in Caco-2 Cells

Background. Allicin has anti-inflammatory, antioxidative and proapoptotic properties. Aims. To evaluate the effects and investigate the mechanism of allicin on trinitrobenzenesulfonic acid-induced colitis, specifically with mesalazine or sulfasalazine. Methods. 80 rats were divided equally into 8 groups: control; trinitrobenzenesulfonic acid; allicin prevention; allicin; mesalazine; sulfasalazine; allicin + sulfasalazine, and mesalazine + allicin. Systemic and colonic inflammation parameters were analysed. In addition, protein and culture medium of Caco-2 cells treated with various concentrations of IL-1β or allicin were collected for investigation of IL-8, NF-κB p65 P38, ERK, and JNK. One-way ANOVA and Kruskal-Wallis H test were used for parametric and nonparametric tests, respectively. Results. Allicin reduced the body weight loss of trinitrobenzenesulfonic acid-induced rats, histological score, serum TNF-α and IL-1β levels, and colon IL-1β mRNA level and induced serum IL-4 level, particularly in combination with mesalazine. In addition, 1 ng/mL IL-1β stimulated the P38, ERK, and JNK pathways, whereas pretreatment with allicin depressed this phenomenon, except for the ERK pathway. Conclusions. The inflammation induced by trinitrobenzenesulfonic acid is mitigated significantly by allicin treatment, particularly combined with mesalazine. Allicin inhibits the P38 and JNK pathways and the expression of NF-κB which explained the potential anti-inflammatory mechanisms of allicin

In vivo Imaging of a Novel Strain of Bacteroides fragilis via Metabolic Labeling

Non-toxigenic Bacteroides fragilis is regarded as a potential candidate for probiotic owing to its various advantages. We previously isolated a new strain of B. fragilis (ZY-312) and verified its biosafety and capability of inhibiting the growth of pathogens in vivo. However, the colonization of ZY-312 in gastrointestinal (GI) tract remains to be determined. To track the colonization of ZY-312, mice were gavaged with ZY-312 labeled by means of metabolic oligosaccharide engineering and bioorthogonal click chemistry or given AF647-dibenzocyclooctyne (DIBO) directly. Then the fluorescence was detected in GI tract, spleen and kidneys. Results showed that ZY-312 could be labeled by metabolic oligosaccharide engineering, and the optimal incubation time with AF647-DIBO was 5 h in vitro. Following oral gavage with AF647-DIBO labeled ZY-312 or AF647-DIBO alone, mice were subjected to in vivo imaging and the fluorescence intensity was similar in both groups 3 h, 6 h, and 12 h post the gavage. The fluorescence of AF647-DIBO group disappeared 24 h post gavage which was probably due to the excretion via GI tract. While the fluorescence of AF647-DIBO labeled ZY-312 retained in the cecum for as long as 48 h. Immunofluorescence assay further confirmed that labeled ZY-312 transiently colonized not only in cecum but also in stomach, ileum and colon of mice 48 h post-gavage and that no massive accumulation of ZY-312 was detected in other organs such as kidneys and spleen. In conclusion, ZY-312 could transiently colonize in GI tract, mainly in cecum, for at least 48 h, and it hardly disseminate to other organs, which shed new light on the future development of B. fragilis as a probiotic product

Bacteroides fragilis Protects Against Antibiotic-Associated Diarrhea in Rats by Modulating Intestinal Defenses

Antibiotic-associated diarrhea (AAD) is iatrogenic diarrhea characterized by disruption of the gut microbiota. Probiotics are routinely used to treat AAD in clinical practice; however, the effectiveness and mechanisms by which probiotics alleviate symptoms remain poorly understood. We previously isolated a non-toxic Bacteroides fragilis strain ZY-312, which has been verified to be beneficial in certain infection disorders. However, the precise role of this commensal bacterium in AAD is unknown. In this study, we successfully established an AAD rat model by exposing rats to appropriate antibiotics. These rats developed diarrhea symptoms and showed alterations in their intestinal microbiota, including overgrowth of some pathogenic bacteria. In addition, gastrointestinal barrier defects, indicated by compromised aquaporin expression, aberrant tight junction proteins, and decreased abundance of mucus-filled goblet cells, were also detected in ADD rats compared with control animals. Of note, oral treatment with B. fragilis strain ZY-312 ameliorated AAD-related diarrhea symptoms by increasing the abundance of specific commensal microbiota. Interestingly, we demonstrated that these changes were coincident with the restoration of intestinal barrier function and enterocyte regeneration in AAD rats. In summary, we identified a potential probiotic therapeutic strategy for AAD and identified the vital roles of B. fragilis strain ZY-312 in modulating the colonic bacterial community and participating in microbiota-mediated epithelial cell proliferation and differentiation