Intestinal metabolite xylulose inhibits colorectal cancer by inducing apoptosis through the MAPK signalling pathway.

BACKGROUND: The intestinal metabolites are involved in the initiation, progression and metastasis of colorectal cancer (CRC). They are a potential source of agents for cancer therapy. Our previous study identified altered faecal metabolites between CRC patients and healthy volunteers. However, no specific metabolite was clearly illustrated for CRC therapy. RESULTS: We found that the level of xylulose was lower in the stools of CRC patients than in those of healthy volunteers. Xylulose inhibited cell growth without affecting the cell cycle by inducing apoptosis in CRC cells, which was evidenced by increased expression of the proapoptotic proteins C-PARP and C-Caspase3 and decreased expression of the antiapoptotic protein BCL-2 in CRC cells. Mechanistically, xylulose reduced the activity of the MAPK signalling pathway, represented by reduced phosphorylation of JNK, ERK, and P38. Furthermore, an ALI model was used to show the tumour killing ability of xylulose on human CRC spheres, as well as human colorectal adenoma (AD) spheres. CONCLUSION: Xylulose inhibits CRC growth by inducing apoptosis through attenuation of the MAPK signalling pathway. These results suggest that xylulose may serve as an effective agent for CRC therapy.

Low Abundance of Lactococcus lactis in Human Colorectal Cancer Is Associated with Decreased Natural Killer Cells.

A limited number of studies have demonstrated the role of Lactococcus lactis (L. lactis) in human colorectal cancers (CRCs). The association of L. lactis abundance with the density of natural killer (NK) cells has not been investigated before. In this study, the L. lactis abundance in 60 CRC specimens, 20 adenoma (AD) specimens, and 29 normal colorectal tissues (NCs) specimens was investigated using the fluorescence in situ hybridization of 16S ribosomal RNA. The density of NK cells was detected using immunofluorescence in 28 CRC specimens, 12 AD specimens, and 22 NC specimens. The presence of L. lactis in NCs (48.28%) was detected significantly higher than that in the AD (20.00%, P = .044) and CRC (23.33%, P = .018) specimens. The abundance of L. lactis in NCs (32.73 ± 7.24) was also found to be significantly higher than that in AD (8.91 ± 5.89, P = .029) and CRC (5.63 ± 1.67, P = .003) specimens. In addition, the density of NKp30+ NK cells in NCs (51.14 ± 4.84) was significantly higher than that in the AD (6.10 ± 1.31) and CRC (1.72 ± 0.40) specimens (P < .001). Moreover, a positive association of L. lactis abundance with NKp30+ NK cells density in the colorectal samples (P < .001) was observed. The low abundance of L. lactis in the CRC tissues was associated with the decreased NK cells, which suggested that this might contribute to the progression of CRC by decreasing the number of NK cells.Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.1944649.

Twenty years of research on HPV vaccines based on genetically modified lactic acid bacteria: an overview on the gut-vagina axis.

Most cervical cancer (CxCa) are related to persistent infection with high-risk human papillomavirus (HR-HPV) in the cervical mucosa, suggesting that an induction of mucosal cell-mediated immunity against HR-HPV oncoproteins can be a promising strategy to fight HPV-associated CxCa. From this perspective, many pre-clinical and clinical trials have proved the potential of lactic acid bacteria (LAB) genetically modified to deliver recombinant antigens to induce mucosal, humoral and cellular immunity in the host. Altogether, the outcomes of these studies suggest that there are several key factors to consider that may offer guidance on improvement protein yield and improving immune response. Overall, these findings showed that oral LAB-based mucosal HPV vaccines expressing inducible surface-anchored antigens display a higher potential to induce particularly specific systemic and mucosal cytotoxic cellular immune responses. In this review, we describe all LAB-based HPV vaccine investigations by reviewing databases from international studies between 2000 and 2020. Our aim is to promote the therapeutic HPV vaccines knowledge and to complete the gaps in this field to empower scientists worldwide to make proper decisions regarding the best strategies for the development of therapeutic HPV vaccines.

Near-focus mode for accurate operation during endoscopic submucosal tunneling procedure.

INTRODUCTION: When using the endoscopic submucosal tunnel technique (ESTT), the working space in the submucosal tunnel is limited, and the visual field is obscured during close inspection or hemostasis. We aimed to evaluate the efficacy and safety of near-focus mode technique for accurate operation during the submucosal tunneling endoscopic procedure. MATERIAL AND METHODS: A retrospective two-center study was designed. A total of 51 patients undergoing ESTT procedures with near-focus mode (n = 29) or traditional mode (n = 22) between February 2016 and May 2019 were included in this study. RESULTS: When using the near-focus mode during the ESTT procedure, it is convenient to ensure a clear image and accurate operation. Adverse events occurred more frequently in the traditional group than in the near-focus group (45.5% vs 17.2%, p = .036). The near-focus group exhibited a lower rate of bleeding compared to the traditional group (0 vs 18.2%, p = .029). Furthermore, the mean hospital stay after the procedure was shorter in the near-focus group than in the traditional group (5.7 days vs 6.7 days, p = .013). CONCLUSIONS: The visual field is more clearly exposed during submucosal tunneling when using the near-focus mode than when using traditional procedures. This technique appears to be more efficient and secure than the traditional ESTT procedure.

Association of Helicobacter bilis Infection with the Development of Colorectal Cancer.

The role of Helicobacter_bilis (H.bilis) in the development of inflammatory bowel disease (IBD) and colitis-associated carcinogenesis (CAC) has seldom been investigated. We examined the abundance of H.bilis in 58 colorectal cancers (CRCs), 20 IBDs, 40 cases of normal colorectal mucosa (NCs), and 20 adenomas (ADs) by 16S rRNA fluorescence in situ hybridization (FISH). Number of CD4+CD45RB+T cell and expression of IFN-γ and TNF-α in these tissues was determined by immunofluorescence. The abundance of H.bilis was significantly higher in CRCs than that in IBDs (P = 0.006), ADs (P < 0.001) and NCs (P < 0.0001). The abundance of H.bilis in IBDs was significantly higher than that in ADs (P = 0.013). Moreover, the average number of CD4+CD45RB+T cell was significantly higher in CRCs than that in IBDs (P = 0.017) and NCs (P = 0.009). In addition, there was a positive correlation between the H.bilis abundance and density of CD4+CD45RB+T cells in 30 colorectal tissues (P < 0.0001). The frequency of co-staining for CD4+CD45RB+T cells and IFN-γ was significantly higher in H.bilis positive group than that in H.bilis negative group (P = 0.002). H.bilis may play a role in the initiation of IBD and CAC, possibly through promoting the transformation of T cells into CD4+CD45RB+T cells and increasing the expression of proinflammatory cytokines IFN-γ.

Intervention on gut microbiota may change the strategy for management of colorectal cancer.

Dysbiosis in the gut microbiota composition due to environmental or genetic variations can disrupt the immune system and may promote several diseases such as colorectal cancer (CRC). Gut microbiota can alter the toxicity and efficiency of an extensive range of CRC treatment methods, especially surgery, chemotherapy, radiotherapy, and immunotherapy. The recent scientific evidence suggested that gut microbiota modulation exhibits an essential positive influence on inhibition and treatment of CRC. The literature survey revealed that modulating the gut microbiota composition by probiotics, prebiotics, and diets protects CRC patients from treatment-associated adverse effects. This review summarizes the recent advancements in the association between interventions on gut microbiota and CRC to provide innovative strategies for enhancing the safety and efficiency of CRC therapy.

Characteristics and publication status of gastrointestinal endoscopy clinical trials registered in ClinicalTrials.gov.

BACKGROUND AND AIMS: This study aimed to examine the fundamental characteristics of gastrointestinal (GI) endoscopy trials and evaluate their publication status. METHODS: A cross-sectional analysis was performed in the ClinicalTrials.gov database, and then the PubMed, Medline, Google Scholar, and Embase databases were searched. A dataset containing GI endoscopy clinical studies from ClinicalTrials.gov registered until November 24, 2017, was downloaded. Data of observational and interventional studies were extracted and analyzed. Publications in peer-reviewed journals were examined for completed trials, and factors associated with publication were identified. RESULTS: A total of 1338 of 253,777 clinical trials were assigned into GI endoscopy, of which 1018 were interventional and 320 were observational studies. Of all the trials, those from the USA comprised the largest percentage (n = 377, 28.18%). The most common field for registered trials was gastroscopy (n = 436, 32.6%), followed by colonoscopy (n = 215, 16.1%), endoscopic ultrasound (n = 186, 13.9%), endoscopic retrograde cholangiopancreatography (n = 176, 13.1%), and novel endoscopic procedure (n = 103, 7.7%). A total of 501 trials were completed before November 25, 2015, 281 (56.1%) of which were published. The median time from study completion to publication was 21 months (interquartile range, 12-32 months). Trials that were comprised of medium sample sizes (150-1000 subjects), conducted in Europe or Asia and other countries, and single or quadruple blinded were more likely to be published. CONCLUSIONS: GI endoscopy is rapidly evolving in clinical applications. Most clinical trials in GI endoscopy are published promptly. These findings demonstrated that investigators are active in performing and communicating the results of clinical trials in the field of GI endoscopy. In the future, the sample size calculation should be presented in detail in the registration system to maintain trial reporting transparency.

Endoscopic management of iatrogenic gastrointestinal defects with the over-the-scope clip (OTSC) system: an updated systematic review.

BACKGROUND: Management of iatrogenic gastrointestinal (GI) defects traditionally required surgical interventions. Recently, the over-the-scope-clip system (OTSC) has been reported to be effective for GI defects. So we aimed to conduct an updated systematic review to evaluate the clinical safety and efficacy of the OTSC system for the management of iatrogenic GI defects. MATERIAL AND METHODS: Studies published in PubMed, Embase and Cochrane library from January 2006 to December 2018 were searched. The literature was selected independently by two reviewers according to inclusion and exclusion criteria. The statistical analysis was carried out using Comprehensive Meta-Analysis software version 3.0. RESULTS: A total of 12 studies including 191 patients with iatrogenic GI defects were identified. The major causes for iatrogenic GI defects were endoscopic submucosal dissection (n = 79) and endoscopic mucosal resection (n = 31). Pooled technical success was achieved in 182 patients (89.1%; 95% confidence interval (CI), 81.6%-93.8%, I2 =41.06%), and the pooled clinical success was achieved in 170 patients (85.2%; 95% CI, 71.9%-92.8%, I2=58.92%). Two patients (1%) suffered complications after OTSC system procedures. CONCLUSIONS: Our study revealed that endoscopic closure of iatrogenic GI defects by the OTSC system was a safe and effective approach. Further randomized controlled trials are warranted to compare the OTSC system to other treatment modalities.

Gut microbiota-derived metabolites and colorectal cancer: New insights and updates.

Abundant evidence from in-vitro as well as in-vivo studies supports the gut microbiota-derived metabolites as crucial executors of diet effect on the host physiology. As such, a number of microbiota-derived metabolites produced from diet have been connected to complex forms of human diseases such as colorectal cancer (CRC). Despite current unresolved questions concerning molecular mechanisms between metabolites, host signaling pathways, and CRC, some new progresses promise continued advancement of the field. Therefore, clarification of the molecular events underlying which metabolites may regulate proliferation of colonocytes will hopefully open up new avenues for seeking the possibilities affecting host health and exploitation of these capabilities for therapeutic purpose. In this Review, we will discuss recent insights into contributions of the gut microbiota-derived metabolites to CRC and argue that the cumulative effects of metabolites should be considered with the intention of better predict and prevent cancer progression. We will also discuss the signaling pathways induced by specific metabolites toward down-regulation and/or up-regulation of immune system that eventually trigger progression and/or inhibition of CRC.

Inter-kingdom signaling between gut microbiota and their host.

The crosstalk between prokaryotic bacteria and eukaryotic gut epithelial cells has opened a new field for research. Quorum sensing system (QS) molecules employed by gut microbiota may play an essential role in host-microbial symbioses of the gut. Recent studies on the gut microbiome will unveil evolved mechanisms of the host to affect bacterial QS and shape bacterial composition. Bacterial autoinducers (AIs) could talk to the host's gut by eliciting proinflammatory effects and modulating the activities of T lymphocyte, macrophage, dendritic cells, and neutrophils. In addition, the gut mucosa could interfere with bacterial AIs by degrading them or secreting AI mimics. Moreover, bacterial AIs and gut hormones epinephrine and noradrenaline may be interchangeable in the crosstalk between the microbiota and human gut. Therefore, inter-kingdom signaling between gut microbiota and host may provide a novel target in the management of gut microbiota-related conditions or diseases in the future.

Bibliometric analysis of the 100 most-cited articles in the field of hepatology.

OBJECTIVE: Bibliometric search of citation classics can function as a tool to identify extraordinary landmark articles and advanced research studies. We aimed to examine and characterize the 100 most-cited published articles in the field of hepatology. PATIENTS AND METHODS: A comprehensive list of the 100 most-cited articles published from 1950 to 2017 in the field of hepatology was compiled after searching the Web of Science with relevant terms, including "liver," "hepatitis," "hepatic," "hepatocellular," "hepatology," "cirrhosis," and "steatohepatitis." The articles were ranked according to their citation counts and were evaluated for characteristics including country, institution, authorship, publication year, subspecialty and others. RESULTS: The database search returned 323,291 articles associated with liver disease published between 1950 and 2017. The 100 most-cited articles were from 21 major journals, with the highest number of articles being published in Hepatology (n=20). The average number of citations of the 100 most-cited articles was 1946.8; among these articles, the most frequently cited article received 5515 citations, and the least frequently cited article received 1155 citations. In total, 60 were original articles among the 100 most-cited articles. The most frequently represented specialties were hepatitis, hepatocellular carcinoma, and nonalcoholic fatty liver disease, which accounted for 53.3%, 23.3%, and 11.7% of these articles, respectively. DISCUSSION: Our study identified citation classics and provided a review of the most advanced studies in the field of hepatology. This can help to guide clinical treatment and future academic research resulting in advancements in hepatology.

Microbiota Diversity in Human Colorectal Cancer Tissues Is Associated with Clinicopathological Features.

AIM: Few evidences are available regarding the link between microbiota composition in the human colorectal cancer (CRC) tissues and the patients' clinicopathological features. METHODS: Microbiota diversity in CRC tissues (n = 30) were profiled and compared by high-throughput sequencing with clinicopathological features, including tumor location, differentiation degree, metastasis, and CRC patients' gender and age. RESULTS: Many bacteria with significant difference in abundance were identified associated with these clinicopathological features (P < 0.05). There was a significant difference in microbial composition between right colon cancers (RCa) vs. left colon cancers (LCa), RCa vs. rectal cancers (P < 0.05). The amount of Fusobacteria was significantly higher in LCa, moderately and poorly differentiated cancers (MPD), and young patients (<60 years), compared to RCa, well differentiated cancers (WD) and elder patients (>60 years), respectively (P < 0.05). Helicobacter spp. in RCa and MPD patients was significantly higher than in LCa and WD patients (P < 0.05). Firmicutes in non-lymph node metastasis (LNM) patients was significantly lower than in LNM patients (P < 0.05). CONCLUSION: The different microbiota composition in the CRCs was associated with patients' clinicopathological features, which could be a consequence of microflora diversity.

Clinical outcomes of lumen-apposing metal stent in the management of benign gastrointestinal strictures: a systematic review and meta-analysis.

Background and aims: Lumen-apposing metal stent (LAMS) have been considered as a viable alternative to treat benign gastrointestinal (GI) strictures. We aimed to determine the efficacy and safety of LAMS for benign GI strictures. Methods: Medline, Embase, Cochrane, and PubMed databases were searched using the keywords 'benign stricture', 'gastrointestinal stricture', 'lumen-apposing metal stent' and related terms on December 2018. Articles were selected for review by two authors independently according to predefined inclusion criteria and exclusion criteria. A meta-analysis using a random effects model was performed. Results: Six studies with a total of 144 patients were included in the final analysis (60 males, 41.7%). Overall, the pooled technical success rate was 98.3% [95% confidence interval (CI): 0.962-1.004], clinical success rate was 73.8% (95% CI: 0.563-0.912) and adverse events rate was 30.6% (95% CI: 0.187-0.425). The most common complication associated with LAMS for benign GI strictures was migration, and the pooled events rate was 10.9% (95% CI: 0.058-0.160). According to locations of stricture, subgroup analysis was performed in terms of clinical success [Esophagogastric: 63.9% (95% CI: 0.365-0.914); Gastroduodenal: 67.4% (95% CI: 0.421-0.927); Gastrojejunal: 78% (95% CI: 0.638-0.922); Pylorus: 77.6% (95% CI: 0.551-1.002); Colonic: 85.3% (95% CI: 0.515-1.191)]. Conclusions: Although the safety of LAMS placement in benign GI strictures is not very satisfactory, it is associated with a low migration rate. LAMS can achieve clinical symptom improvement or resolution in most patients with benign GI strictures, and it might be an alluring prospect for treating patients with this difficult condition.

Efficacy and safety of submucosal tunneling endoscopic resection for upper gastrointestinal submucosal tumors with more than 1-year' follow-up: a systematic review and meta-analysis.

Objectives: Submucosal tunneling endoscopic resection (STER) is a novel therapeutic approach for upper gastrointestinal submucosal tumors (SMTs) especially for tumors originating from the muscularis propria layer. Presently, several studies have reported the efficacy and safety of STER for SMTs. Therefore, we conducted this study to review the clinical outcomes of STER with more than 1-year' follow-up duration. Materials and methods: Medline, Embase and Cochrane databases were searched on November 2018 to identify studies reporting STER for SMTs. Weighted pooled rates were calculated for en bloc resection, complete resection and adverse event (AE). Risk ratios (RR) were calculated and pooled to compare STER with thoracoscopic enucleation (TE). Results: A total of 701 patients with 728 lesions from 12 original studies were review. Pooled WPR for en bloc resection of STER was 86.3% (95% CI: 74.5-93.1%), (I2=82.5). Pooled WPR for complete resection of STER was 97.7% (95% CI: 92.8-99.3%), (I2=77.6). WPR for AE was 18.3% (95% CI: 9.7-31.6%), (I2=90.6%). Two studies with 292 patients compared the performance of STER with TE. Pooled RR for en bloc resection was 1.02 (95% CI: 0.95-1.09). Pooled RR for complete resection was 1.0 (95% CI: 0.98-1.03). Pooled RR for AE was 0.82 (95% CI: 0.33-2.05). Conclusions: Our study showed that STER has relatively long-term efficacy for treating upper gastrointestinal SMTs, and the incidence of AE was not low for STER, but all of them can be managed conservatively.

Clinical outcomes of over-the-scope-clip system for the treatment of acute upper non-variceal gastrointestinal bleeding: a systematic review and meta-analysis.

BACKGROUND: Conventional endoscopic treatments can't control bleeding in as many as 20% of patients with non-variceal gastrointestinal (GI) bleeding. Recent studies have shown that over-the-scope-clip (OTSC) system allowed for effective hemostasis for refractory GI bleeding lesions. So we aimed to conduct a systematic review to evaluate the effectiveness and safety of the OTSC system for management of acute non-variceal upper GI bleeding. METHOD: A comprehensive literature search was conducted on PubMed, EMBASE, and Cochrane Library covering the period from January 2007 to May 2019. The literature was selected independently by two reviewers according to the inclusion and exclusion criteria. The statistical analysis was carried out using Comprehensive Meta-Analysis software version 3.0. RESULTS: A total of 16 studies including 769 patients with 778 GI bleeding lesions were identified. Pooled technical success was achieved in 761 lesions [95.7%; 95% confidence interval (CI), 93.5-97.2%], and the pooled clinical success was achieved in 666 lesions (84.2, 95% CI, 77.4-89.2%). The incidence of re-bleeding was reported in 81 patients and the post-procedure mortality was 10.9% (n = 84). Only 2 (0.3%) patients occurred complications after OTSC system procedure. CONCLUSIONS: Our study demonstrated that the OTSC system was a technically feasible modality and highly efficacious in achieving hemostasis in acute non-variceal upper gastrointestinal bleeding.

Fusobacterium nucleatum promotes M2 polarization of macrophages in the microenvironment of colorectal tumours via a TLR4-dependent mechanism.

Fusobacterium nucleatum (Fn) has been shown to promote colorectal cancer (CRC) development by inhibiting host anti-tumour immunity. However, the impact of Fn infection on macrophage polarization and subsequent intestinal tumour formation as well as the underlying molecular pathways has not been investigated. We investigated the impact of Fn infection on macrophage polarization in human CRCs and cultured macrophages as well as the effects on macrophage phenotype and intestinal tumour formation in ApcMin/+ mice. We also examined whether macrophage-polarized activation challenged by Fn infection via a TLR4-dependent mechanism involved the IL-6/STAT3/c-MYC signalling cascade. Our data showed that macrophages are a major tumour-infiltrating immune cell type in human CRCs with Fn infection (P < 0.001). Fn infection increased M2 polarization of macrophages in vitro and in vivo, leading to intestinal tumour growth in ApcMin/+ mice. Moreover, Fn infection induced high expression of TLR4, IL-6, STAT3, p-STAT3, and c-MYC in cultured macrophages challenged with Fn, which was blocked by TAK-242 pre-treatment (P < 0.05). Interestingly, c-MYC protein was mainly co-localized with CD206+ M2 macrophages with Fn infection. In conclusion, we show that Fn infection increased M2 polarization of macrophages in vitro and in vivo. Furthermore, Fn infection enhanced colorectal tumour growth in a TLR4-dependent manner involving activation of the IL-6/p-STAT3/c-MYC signalling pathway. For the first time, our results indicate an immunosuppressive effect of Fn by promoting M2 polarization of macrophages through a TLR4-dependent mechanism, which may serve as a promising target for immunotherapy of Fn-related CRC.

Fusobacterium nucleatum Potentiates Intestinal Tumorigenesis in Mice via a Toll-Like Receptor 4/p21-Activated Kinase 1 Cascade.

BACKGROUND: The underlying pathogenic mechanism of Fusobacterium nucleatum in the carcinogenesis of colorectal cancer has been poorly understood. METHODS: Using C57BL/6-ApcMin/+ mice, we investigated gut microbial structures with F. nucleatum, antibiotics, and Toll-like receptor 4 (TLR4) antagonist TAK-242 treatment. In addition, we measured intestinal tumor formation and the expression of TLR4, p21-activated kinase 1 (PAK1), phosphorylated-PAK1 (p-PAK1), phosphorylated-ß-catenin S675 (p-ß-catenin S675), and cyclin D1 in mice with different treatments. RESULTS: Fusobacterium nucleatum and antibiotics treatment altered gut microbial structures in mice. In addition, F. nucleatum invaded into the intestinal mucosa in large amounts but were less abundant in the feces of F. nucleatum-fed mice. The average number and size of intestinal tumors in F. nucleatum groups was significantly increased compared to control groups in ApcMin/+ mice (P < 0.05). The expression of TLR4, PAK1, p-PAK1, p-ß-catenin S675, and cyclin D1 was significantly increased in F. nucleatum groups compared to the control groups (P < 0.05). Moreover, TAK-242 significantly decreased the average number and size of intestinal tumors compared to F. nucleatum groups (P < 0.05). The expression of p-PAK1, p-ß-catenin S675, and cyclin D1 was also significantly decreased in the TAK-242-treated group compared to F. nucleatum groups (P < 0.05). CONCLUSIONS: Fusobacterium nucleatum potentiates intestinal tumorigenesis in ApcMin/+ mice via a TLR4/p-PAK1/p-ß-catenin S675 cascade. Fusobacterium nucleatum-induced intestinal tumorigenesis can be inhibited by TAK-242, implicating TLR4 as a potential target for the prevention and therapy of F. nucleatum-related colorectal cancer.

Invasive Fusobacterium nucleatum may play a role in the carcinogenesis of proximal colon cancer through the serrated neoplasia pathway.

The prevalence of invasive Fusobacterium nucleatum (Fn) within the serrated neoplasia pathway of the proximal colon has seldom been investigated. We examined the invasive Fn and bacterial biofilms in 35 proximal hyperplastic polyps (HPs), 33 sessile serrated adenomas (SSAs), 48 proximal colorectal cancers (CRCs) and 10 matched metastatic lymph nodes using 16S rRNA fluorescence in situ hybridization (FISH). Samples of normal mucosa, traditional adenomas (TAs), distal HPs, distal CRCs and matched lymph nodes with or without metastases were used as controls. The prevalence of invasive Fn within proximal HPs (65.7%) and SSAs (78.8%) were significantly higher than that of proximal TAs (28.9%) and distal TAs (24.4%; p < 0.05). Invasive Fn was detected in markedly more proximal CRCs (89.6%) than in distal CRCs (42.2%; p < 0.05). Moreover, invasive Fn was detected in a significantly higher proportion of matched metastatic lymph nodes (100%) than that within nonmetastatic lymph nodes (40.0%; p < 0.001). Bacterial biofilms were found on 52.1% of proximal CRCs, 55.6% of distal CRCs and 48.5% of SSAs. Biofilms were positive for Fn in 47.9% of proximal CRCs, 48.9% of distal CRCs and 27.3% of SSAs. However, the presence of Fn in biofilms was not related to invasive Fn within colorectal tissues (p = 0.415). Invasive Fn may play a role in the carcinogenesis of proximal colon developing via the serrated neoplasia pathway, but might have a less important role in the TA-carcinoma sequence. Bacterial biofilms may not contribute to the invasion of Fn into tumor tissues.

Endoplasmic reticulum stress may not be involved in intestinal epithelial cell apoptosis in experimental acute pancreatitis.

OBJECTIVES: To investigate whether endoplasmic reticulum (ER) stress is activated in the intestinal epithelium of acute pancreatitis (AP), and whether it is one of the inducing factors of the intestinal epithelial cell apoptosis in AP. METHODS: Twenty-four rats were randomly divided into two groups. AP was induced via retrograde injection of 3 % sodium taurocholate into the pancreatic duct. As a control group, rats received a sham operation. Forty-eight hours after the operation, the ultrastructural changes of ileal epithelial cells were investigated by transmission electron microscope. The protein expressions of GRP78, CHOP, caspase-12, and JNK in the ileal epithelium were determined by immunohistochemistry, and apoptosis was determined by TdT-mediated dUTP nick end labeling. The mRNA expressions of GRP78, CHOP, caspase-12, and JNK in the ileal epithelium were determined using quantitative RT-PCR. RESULTS: The ileal epithelium in rats with AP had significantly higher apoptotic cells compared with that of the control rats (P < 0.05). ER stress was activated in the ileal epithelium, which was characterized by dilated, irregular ER and upregulated expressions of GRP78 mRNA and protein. The mRNA and protein expressions of CHOP, caspase-12, and JNK in rats with AP were similar to that in the control rats (P > 0.05). CONCLUSIONS: ER stress is induced in intestinal epithelium during AP; however, ER stress is not likely to be involved in the apoptosis of the intestinal epithelium during AP.