TYRO3 promotes tumorigenesis and drug resistance in colorectal cancer by enhancing the epithelial-mesenchymal transition process.

Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide. Although considerable advances in CRC treatment have been achieved, effective treatment improvement has hit a bottleneck. This study demonstrated that TYRO3 expression was aberrantly increased in CRC tissues with prognosis association. The prediction model of prognosis for CRC patients was constructed based on TYRO3 expression. The model suggested that the TYRO3 level is crucial to the final prediction results. We observed that knockdown TYRO3 expression could inhibit the proliferation and migration ability and reverse the drug resistance by constructing drug-resistant CRC cell lines. In vivo experiments also confirmed this conclusion. Thus, targeting TYRO3 combined with 5-Fu treatment could provide a better therapeutic effect. Additionally, TYRO3 could inhibit the EMT process by down-regulating ENO1, which may be achieved by interfering with energy metabolism in cancer cells. Therefore, the current study provides a theoretical basis for TYRO3 in drug-resistance of CRC cells and highlights a new strategy for CRC-targeted therapy.

Misdiagnosis of acute pancreatitis in a patient with foreign body ingestion: a case report and literature review.

Foreign body ingestion is a rare but important clinical event. We herein describe a patient who was misdiagnosed with acute pancreatitis after inadvertent ingestion of a toothpick while drunk. The toothpick penetrated the stomach and migrated to the pancreas, resulting in abdominal pain for nearly 1 month. We present the clinical manifestations, diagnosis, and treatment of the patient and summarize the characteristics of patients with foreign body ingestion by a systematic literature review. This report illustrates an unusual of misdiagnosed acute pancreatitis caused by foreign body. This case reminds us to make full use of different diagnostic tools and multidisciplinary collaboration to leverage their complementary strengths and improve the diagnostic accuracy.

Leaky Gut in IBD: Intestinal Barrier-Gut Microbiota Interaction.

Inflammatory bowel disease (IBD) is a global disease that is in increasing incidence. The gut, which contains the largest amount of lymphoid tissue in the human body, as well as a wide range of nervous system components, is integral in ensuring intestinal homeostasis and function. By interacting with gut microbiota, immune cells, and the enteric nervous system, the intestinal barrier, which is a solid barrier, protects the intestinal tract from the external environment, thereby maintaining homeostasis throughout the body. Destruction of the intestinal barrier is referred to as developing a "leaky gut," which causes a series of changes relating to the occurrence of IBD. Changes in the interactions between the intestinal barrier and gut microbiota are particularly crucial in the development of IBD. Exploring the leaky gut and its interaction with the gut microbiota, immune cells, and the neuroimmune system may help further explain the pathogenesis of IBD and provide potential therapeutic methods for future use.

Propensity score matching analysis to evaluate efficacy of polyethylene oxide adhesive on preventing delayed bleeding after gastric endoscopic submucosal dissection.

Regardless of technical advancements, delayed bleeding is still a common adverse event after gastric endoscopic submucosal dissection (ESD), often occurring in the early postoperative phase. This study aimed to evaluate the efficacy of a newly designed polyethylene oxide (PEO) adhesive for preventing delayed gastric bleeding. Patients who underwent gastric ESD between December 2017 and December 2020 at three Chinese institutions were retrospectively reviewed. Patients receiving PEO application on gastric post-ESD ulcers were included in the PEO group, and patients without this procedure were included in the control group. To minimize potential bias, propensity score matching was performed, and sex, age, lesion size, lesion morphology, ulceration, localization, procedure time, frequency of major intraoperative bleeding, resected specimen size, lesion histopathology, submucosal invasion and the taking of antithrombotic drugs were included as matching factors. The incidence of delayed bleeding and time to bleeding were compared between both groups. After propensity score matching, 270 patients (135 per group) were included in the analysis. The delayed bleeding rate in the PEO group was significantly lower than that in the control group (1.5%, 2/135 vs. 8.9%, 12/135, P = 0.006). The median time (range) to bleeding was 4.5 (4-5) days in the PEO group and 2 (1-15) days in the control group, with no significant difference (P = 0. 198). PEO demonstrated a significant effect in reducing the rate of delayed bleeding. Further study is warranted to confirm the efficacy of PEO for bleeding that occurs in the early phase after gastric ESD.

Bidirectional regulation of bile acid on colorectal cancer through bile acid-gut microbiota interaction.

Colorectal cancer (CRC) is now the third most common malignancy and the second leading cause of cancer death globally. Bile acid has bidirectional regulatory effects on CRC and influences its progression by interacting with gut microbiota. In this review, we provide evidence for bidirectional regulation of bile acid on CRC at multi-level and discuss the communication of gene, immune, metabolism and diet in the context of CRC with bile acid-gut microbiota interaction. The study on bidirectional regulation of bile acid is helpful to provide a more comprehensive and in-depth understanding of CRC pathogenesis and expect to be a new option for the treatment of CRC.

LncRNA LUCAT1 as a Plasma Biomarker for Assessing Disease Activity in Adult Patients with Crohn's Disease.

AIM: To explore the expression of long noncoding RNA (LncRNA) LUCAT1 in adult patients with Crohn's disease (CD) and evaluate the relationship between LncRNA LUCAT1 and the disease activity in Chinese patients with CD. METHODS: Patients with CD and healthy participants (≥18 years old) were enrolled in this study between January 2018 and December 2019. The expression of LncRNA LUCAT1 in plasma samples was evaluated by quantitative reverse transcription-polymerase chain reaction. Basic characteristics of patients with CD were collected, including gender, age, clinical stage, disease behavior, disease location, C-reactive protein (CRP), platelet (PLT), erythrocyte sedimentation rate (ESR), fecal calprotectin (FC), Crohn's disease activity index (CDAI) score, and simplified Crohn's disease endoscopic score (SES-CD). RESULTS: In total, 168 patients with CD and 65 healthy participants (≥18 years old) were enrolled in this study. Among them, ninety patients with clinically active CD, seventy-eight patients with CD in clinical remission, forty-eight patients with endoscopically active CD, thirty patients with endoscopically inactive CD, and sixty-five healthy participants. LncRNA LUCAT1 was increased in plasma of patients with CD compared with the control group. The plasma LncRNA LUCAT1 level of patients with CD both in the clinical and endoscopic active phase was higher than that of both the clinical and endoscopic remission phase. The plasma level of LncRNA LUCAT1 in patients with CD was positively correlated with ESR, CRP, FC, CDAI, and SES-CD. There was no significant correlation between the level of LUCAT1 and platelets. The plasma LncRNA LUCAT1 level in patients with CD had significant differences between severe active patients and mild/moderate active patients. CONCLUSION: The plasma LncRNA LUCAT1 is positively associated with the disease activity in patients with CD, and it may act as a noninvasive biomarker to identify the degree of disease activity.

Evaluation of fecal microbiota transplantation in Parkinson's disease patients with constipation.

Parkinson's disease (PD) is a neurodegenerative disorder and 70-80% of PD patients suffer from gastrointestinal dysfunction such as constipation. We aimed to assess the efficacy and safety of fecal microbiota transplantation (FMT) for treating PD related to gastrointestinal dysfunction. We conducted a prospective, single- study. Eleven patients with PD received FMT. Fecal samples were collected before and after FMT and subjected to 16S ribosomal DNA (rDNA) gene sequencing. Hoehn-Yahr (H-Y) grade, Unified Parkinson's Disease Rating Scale (UPDRS) score, and the Non-Motion Symptom Questionnaire (NMSS) were used to assess improvements in motor and non-motor symptoms. PAC-QOL score and Wexner constipation score were used to assess the patient's constipation symptoms. All patients were tested by the small intestine breath hydrogen test, performed before and after FMT. Community richness (chao) and microbial structure in before-FMT PD patients were significantly different from the after-FMT. We observed an increased abundance of Blautia and Prevotella in PD patients after FMT, while the abundance of Bacteroidetes decreased dramatically. After FMT, the H-Y grade, UPDRS, and NMSS of PD patients decreased significantly. Through the lactulose H2 breath test, the intestinal bacterial overgrowth (SIBO) in PD patients returned to normal. The PAC-QOL score and Wexner constipation score in after-FMT patients decreased significantly. Our study profiles specific characteristics and microbial dysbiosis in the gut of PD patients. FMT might be a therapeutic potential for reconstructing the gut microbiota of PD patients and improving their motor and non-motor symptoms.

The potential therapeutic role of Lactobacillus reuteri for treatment of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic intestinal disease of unknown etiology. However, recent studies have established a pathological role of disordered intestinal microbiota and immune dysregulation. Clinical studies have suggested that the reconstruction of the normal intestinal flora in patients with IBD can reverse the dysbiosis caused by genetic, environmental, dietary, or antibiotic factors to ameliorate the symptoms of IBD. Lactobacillus reuteri is widely present in the intestines of healthy individuals and regulates the intestinal immune system, reducing inflammation through multiple mechanisms. This review summarizes the current knowledge of the role of L. reuteri in maintaining intestinal homeostasis and considers its possible value as a new therapeutic agent for patients with IBD.

The Interaction of GLUT1 and FOXM1 Leads to a Poor Prognosis in Colorectal Cancer.

BACKGROUND: Colorectal Cancer (CRC) is one of the most common fatal diseases with high morbidity. Alteration of glucose metabolism is one of the hallmarks in the development of CRC. Glucose Transporter 1 (GLUT1) is a key rate-limiting protein in hyperactive glucose metabolism and up-regulated in CRC, however, the underlying mechanism of the altered metabolism in CRC is still unknown. METHODS: In this study, immunohistochemical staining was used to evaluate the expression of GLUT1 and FOXM1 in 135 paired CRC and adjacent normal tissues. The association between the expression of GLUT1/FOXM1 and clinicopathological factors was determined and the correlation between GLUT1 and FOXM1 in CRC was investigated. RESULTS: Our results revealed that regardless of tumor location, GLUT1 and FOXM1 were overexpressed in CRC tissues, especially in patients with positive lymph node metastasis and TNM stage III-IV. Furthermore, GLUT1 showed a significantly strong link with FOXM1 in CRC tissue. CONCLUSION: Overexpression of GLUT1 and FOXM1 may play critical roles in CRC leading to a poor prognosis.

Expression analysis and implication of Rab1A in gastrointestinal relevant tumor.

Gastrointestinal cancers have become increasingly prevalent worldwide. Previous studies have reported an oncogenic function of Rab1A in colorectal cancer and hepatocellular carcinomas via the mTOR pathway. However, the exact role of Rab1A in gastrointestinal cancers remains elusive. We detected significantly higher expression of Rab1A in the gastrointestinal tumor tissues compared to that in other cancer types following an in silico analysis of TGCA and GTEX databases. Furthermore, Rab1A was overexpressed in the gastrointestinal tumor tissues compared to the para-tumor tissues. Although Rab1A expression levels were not associated with the tumor-lymph node-metastasis (TNM) stage, Rab1A overexpression in the tumor tissues of a gastric cancer (GC) cohort was strongly correlated with poor prognosis in the patients. In addition, Rab1A knockdown significantly inhibited the in vitro proliferation and migration abilities of GC cells, as well as the growth of GC xenografts in vivo. Furthermore, a positive correlation was observed between Rab1A expression levels and that of different upstream/downstream mTOR targets. Taken together, Rab1A regulates the PI3K-AKT-mTORC1 pathway through the mTORC1 complex consisting of mTORC1, Rheb and Rab1A, and is a promising therapeutic target in GC.

Rab1A promotes proliferation and migration abilities via regulation of the HER2/AKT-independent mTOR/S6K1 pathway in colorectal cancer.

Colorectal carcinoma (CRC) is one of the most common malignancies worldwide and the second leading cause of cancer­related deaths in the US. Recently, Rab1A has been reported to be an activator of mTORC1 and p­S6K1, which is downstream of mTORC1. However, the association between Rab1A and p­S6K1 in CRC remains elusive. In the present study, we first demonstrated that Rab1A was overexpressed in CRC tissues and Rab1A overexpression was positively related to lymph node invasion, degree of differentiation, venous invasion and tumor­node­metastasis (TNM) stage. In both TNM stage I­II and III­IV patients, Rab1A­positive patients had a shorter survival time than Rab1A­negative patients. Furthermore, in univariate and multivariate analyses, only Rab1A expression was verified as an independent prognostic factor for survival in CRC patients. The level of p­S6K1 was markedly high in CRC tissues and Rab1A expression level had a positive association with p­S6K1 level. In addition, high levels of both Rab1A and p­S6K1 were associated with a poorer prognosis compared with low expression of either Rab1A or p­S6K1 level. Moreover, high levels of both Rab1A and p­S6K1 were associated with a poorer prognosis than patients with high levels of either Rab1A or p­S6K1 alone. Finally, knockdown of Rab1A expression inhibited migration and proliferation of SW480 and HCT116 cell lines by targeting regulation of p­S6K1. Thus, our findings indicate that Rab1A plays an important role in CRC and may provide a therapeutic target for CRC, particularly for mTORC1­targeted therapy­resistant cancers.

Correlation of Gli1 and HER2 expression in gastric cancer: Identification of novel target.

HER2 becomes the standard of care for guiding adjuvant treatment of gastric cancer with trastuzumab in recent years. However, the usage of this target agent is still limited because of the resistance to trastuzumab or the negative expression of HER2 in tumor tissues. The Gli1 and HER2 both play an important role in the pathogenesis of gastric cancer. However, the correlation of them is still unclear. Here we found Gli1 and HER2 are highly expressed in gastric cancer tissues, and they are positively related. Next, we found Gli1 positive patients live a shorter survival time no matter HER2 positive or negative. Furthermore, univariate and multivariate analysis revealed that venous invasion, HER2 expression, Gli1 expression were independent prognostic factors for the survival time in gastric cancer. In addition, suppressing the expression level of Gli1 can decrease the cell viability and migration ability in cells and subcutaneous tumors. Finally, we found that HER2 may regulate Gli1 by Akt-mTOR-p70S6K pathway. Inhibit of HER2 and SMO have synergistic effect on reduction of cell viability. In conclusion, Gli1 is a favorable prognostic indicator in gastric cancer. As a novel target, Gli1 worth further study, especially in Her2-targeted therapy-resistant cancers.

Over-expression of small ubiquitin-related modifier-1 and sumoylated p53 in colon cancer.

Here we investigated whether the cellular accumulation of p53 protein caused by over-expression of small ubiquitin-related modifier-1 (SUMO-1) could be used as a predictive marker for prognosis in colon cancer. We detected SUMO-1 and p53 protein levels in 46 cases of colon cancer and adjacent tissues by immunohistochemistry and found that SUMO-1 was expressed at much higher levels in colon cancer compared with that in normal colon tissue. Immunoprecipitation and Western blot analysis revealed that the tumor suppressor p53 was present predominantly in the sumoylated rather than the non-sumoylated form in the colon cancer cell lines. A small interfering RNA targeted to SUMO-1 mRNA sequences was used to observe the levels of the p53 protein. Patients who showed high dual expressions of SUMO-1 and p53 tended to experience metastasis more frequently. These results suggest that the cellular accumulation of p53 protein caused by over-expression of SUMO-1 may be involved in tumor aggressiveness. Multivariate analysis confirmed that the high dual expression of SUMO-1 and p53 was an independent factor for evaluating prognosis. SUMO-1 may be useful as a novel target for therapy in colon cancer as well as a clinical indicator for tumor aggressiveness.

Protective role of uncoupling protein-2 against dextran sodium sulfate-induced colitis.

BACKGROUND AND AIMS: Uncoupling protein-2 (UCP-2) is a negative regulator of reactive oxygen species (ROS) production. We investigated the effect of UCP-2 on disease progression in a murine dextran sodium sulfate (DSS)-induced colitis model, and the expression and distribution of tight junction (TJ) proteins, such as occludin, zonula-1 (ZO-1), claudin-4, and junctional adhesion molecule-1 (JAM-1). METHODS: Male UCP-2(-/-) mice and wild-type littermates were divided into four groups: groups I and II, which comprised each type of mouse, were administered 2.5% DSS dissolved in drinking water to create a colitis model. The control groups (groups III and IV, which comprised each type of mouse) were given normal drinking water. Disease progression was evaluated according to colon length and the disease activity index. The distribution of TJ proteins was detected by immunohistochemical analysis. RESULTS: Compared with wild-type littermates, UCP-2(-/-) mice treated with DSS developed more severe diarrhea, body weight loss (P < 0.01), significantly short colon length, and more inflammatory cell infiltration into the mucosa and submucosa. The level of malondialdehyde in colonic mucosa increased in UCP-2(-/-) mice treated with DSS compared with the wild-type littermates (P < 0.001). The distribution of the ZO-1 and JAM-1 proteins was significantly decreased in the colonic mucosa of UCP-2(-/-) mice compared with the wild-type littermates, whereas occludin and claudin-4 distribution were not different between the UCP-2(-/-) mice and wild-type littermates. CONCLUSIONS: UCP-2 might reduce intestinal inflammatory response through the negative regulation of ROS, and affects the expression and distribution of TJ proteins.

Mitochondrial uncoupling protein 2 expression in colon cancer and its clinical significance.

AIM: To detect the expression of mitochondrial uncoupling protein 2 (UCP2) in colon cancer and analyze the relation between UCP2 expression and clinical pathological features of colon cancer. METHODS: Fifteen colon tissue samples and 15 its adjacent tissue samples were obtained from colon cancer patients during surgical interventions. UCP2 expression was detected with immunohistochemical method in 10 normal controls, 10 hyperplastic polyp patients, 20 tubular adenoma patients and 78 colon cancer patients. Patients with rectal cancer were excluded. Quantitative reverse transcription polymerase chain reaction and Western blotting were used to detect UCP2 expressions in colon cancer tissue samples and its adjacent tissue samples. Relation between UCP2 expression and clinical pathological features of colon cancer was also analyzed. RESULTS: The UCP2 mRNA expression level was four-fold higher in colon cancer tissue samples than in its adjacent tissue samples. The UCP2 protein expression level was three-fold higher in colon cancer tissue samples than in its adjacent normal tissue samples. The UCP2 was mainly expressed in cytoplasm. The UCP2 was not expressed in normal colon mucosa. Strong positive staining for UCP2 with a diffuse distribution pattern was identified throughout the mucosa in colon cancer tissue samples with a positive expression rate of 85.9%. The UCP2 expression level was higher in colon cancer tissue samples at clinical stages III and IV than in those at stage I + II. Univariate analysis showed that the high UCP2 expression level was significantly correlated to colon cancer metastasis (hazard ratio = 4.321, confidence interval = 0.035-0.682, P = 0.046). CONCLUSION: UCP2 is highly expressed in human colon cancer tissue and may be involved in colon cancer metastasis.