Ulcerative colitis (UC) is an immune-mediated chronic intestinal disease, with a pathogenesis that remains incompletely understood. The purpose of this study is to analyze the difference of gene expression between UC patients and healthy controls using Oxford Nanopore Technology's long-read RNA sequencing (ONT-RNA-seq) and to explore how alternative polyadenylation (APA) site selection contributes to UC pathogenesis.

Colon tissue samples from UC and normal controls (NC) were collected, and total RNA was extracted and sequenced using ONT-RNA-seq technology. Various bioinformatics analyses were performed, including differential expression gene (DEG) analysis, functional enrichment analysis, APA site analysis, and prediction miRNAs and RNA binding proteins (RBPs) targets, to explore the molecular mechanism underlying UC.

ONT-RNA-seq analysis revealed that the expression levels of ACSF2, NPY, SLC26A3, BRINP3, and PKLPP2 were significantly lower in UC patients compared to the NC group, while the expression levels of CCL20, CCL21, CD55, IDO1, LCN2, NOS2, CCL11, OLFM4, ANXA1, REG1A, S100A9, SLPI, SPINK1, and AGR2 were significantly higher. Functional enrichment analysis showed that DEGs were closely related to immune and inflammatory responses, which in turn are related to many challenges in the diagnosis and treatment of UC. Mechanistically, APA site selection was found to contribute to the regulation of gene expression in UC, and some APA genes were identified as potential regulators of miRNAs and RBPs. Vene diagram revealed significant overlap between miRNA- and RBP-targeted genes and DEGs, suggesting that APA genes may modulate genes expression in UC through miRNA and RBP targeting. Additionally, five key APA genes--CD38, NCALD, SMIM31, GPX7, and SWAP70--were identified as potentially playing crucial role in UC pathogenesis.

This study provides new insights into the molecular mechanisms of UC through ONT-RNA-seq technology, especially in gene expression regulation and APA site selection.

Circular RNAs (circRNAs) are involved in the pathogenesis of many diseases through competing endogenous RNA (ceRNA) regulatory mechanisms.

To investigate a circRNA-related ceRNA regulatory network and a new predictive model by circRNA to understand the diagnostic mechanism of circRNAs in ulcerative colitis (UC).

We obtained gene expression profiles of circRNAs, miRNAs, and mRNAs in UC from the Gene Expression Omnibus dataset. The circRNA-miRNA-mRNA network was constructed based on circRNA-miRNA and miRNA-mRNA interactions. Functional enrichment analysis was performed to identify the biological mechanisms involved in circRNAs. We identified the most relevant differential circRNAs for diagnosing UC and constructed a new predictive nomogram, whose efficacy was tested with the C-index, receiver operating characteristic curve (ROC), and decision curve analysis (DCA).

A circRNA-miRNA-mRNA regulatory network was obtained, containing 12 circRNAs, three miRNAs, and 38 mRNAs. Two optimal prognostic-related differentially expressed circRNAs, hsa_circ_0085323 and hsa_circ_0036906, were included to construct a predictive nomogram. The model showed good discrimination, with a C-index of 1(> 0.9, high accuracy). ROC and DCA suggested that the nomogram had a beneficial diagnostic ability.

This novel predictive nomogram incorporating hsa_circ_0085323 and hsa_circ_0036906 can be conveniently used to predict the risk of UC. The circRNa-miRNA-mRNA network in UC could be more clinically significant.

Ulcerative colitis (UC) is a chronic inflammatory disorder of unknown aetiology. Gut virome dysbiosis is fundamental in UC progression, although its role in the early phases of the disease is far from fully understood. Therefore, we sought to investigate the role of a virome-associated protein encoded by the Orthohepadnavirus genus, the hepatitis B virus X protein (HBx), in UC aetiopathogenesis.

HBx positivity of UC patient-derived blood and gut mucosa was assessed by RT-PCR and Sanger sequencing and correlated with clinical characteristics by multivariate analysis. Transcriptomics was performed on HBx-overexpressing endoscopic biopsies from healthy donors.C57BL/6 mice underwent intramucosal injections of liposome-conjugated HBx-encoding plasmids or the control, with or without antibiotic treatment. Multidimensional flow cytometry analysis was performed on colonic samples from HBx-treated and control animals. Transepithelial electrical resistance measurement, proliferation assay, chromatin immunoprecipitation assay with sequencing and RNA-sequencing were performed on in vitro models of the gut barrier. HBx-silencing experiments were performed in vitro and in vivo.

HBx was detected in about 45% of patients with UC and found to induce colonic inflammation in mice, while its silencing reverted the colitis phenotype in vivo. HBx acted as a transcriptional regulator in epithelial cells, provoking barrier leakage and altering both innate and adaptive mucosal immunity ex vivo and in vivo.

This study described HBx as a contributor to the UC pathogenesis and provides a new perspective on the virome as a target for tailored treatments.

Ulcerative colitis is a disease of undetermined etiology and treatment. It affects the colon and rectum and typically involves the mucosa, manifesting as continuous areas of inflammation and ulceration. Aloe gel contains more than a hundred potentially active constituents of different classes. This study investigated the effect of aloe gel on experimentally-induced ulcerative colitis. Male Wistar rats were randomly allocated into groups A to F of six rats each. Ulcerative colitis was induced to rats in groups B to F by single intra-colonic administration of 2 mL of 4% acetic acid with a size 6F pediatrics catheter. In contrast, group A received an equivalent volume of normal saline by the same route. Twenty-four hours after induction, rats in groups B and C received normal saline and 1 mg/kg b. wt. daily dose of dexamethasone, respectively. In contrast, those in groups D, E, and F received 20, 40, and 60 mg/kg b. wt. doses of aloe gel, respectively, for 14 days. They were sacrificed 24 h after the last administration. We assessed disease progression by determining the clinical activity index, gross inflammation, histological alterations, the intensity of DNA in colon cells, and tissue level of nitric oxide. All the parameters but one increased significantly in group B rats. The quantitative distribution of DNA in colon cells reduced significantly in this group. Aloe gel doses significantly reversed these changes in a dose-dependent manner. Dexamethasone showed lesser efficacy relative to 60 mg dose of the Aloe gel extract. We conclude that Aloe vera gel has therapeutic potential in the treatment and management of ulcerative colitis. The most significant effects were observed in the groups treated with the highest dose of Aloe gel (60 mg/kg b. wt.). It is also worth noting that the remediated potential of aloe gel in acetic acid-induced UC surpasses that of dexamethasone.

A meta-analysis was conducted on the incidence of colon cancer in patients with ulcerative colitis (UC). This study aimed to evaluate the correlation between UC and colon cancer, and provide a theoretical guidance for clinical diagnoses and treatments of UC.

Articles were searched in Chinese database with "ulcerative colitis", "UC", "colon cancer", "colorectal cancer", "incidence", and "meta-analysis" as the search terms. Articles were searched in English database with "ulcerative colitis", "UC", "colon cancer", "incidence rate", and "meta-analysis" as the search terms. Moreover, articles with the topic of "correlation between UC and colon cancer" were screened. The quality of articles was assessed using Rev Man 5.3 software provided by Cochrane system.

Eleven articles were included, most of which were of medium and high quality. Results of meta-analysis showed that 12,216 patients with UC were included in this study, and 110 patients developed colon cancer. There was statistical heterogeneity (Chi2=103.10, I2=90%, P<0.00001). Random-effect model analyses showed that there were no significant differences between colon cancer in patients with UC and those without colon cancer (Z=12.44, P<0.00001). A systematic review of articles found that the course and development of colon cancer in patients with UC might affect the occurrence of colon cancer. UC was a risk factor for colorectal cancer.

It was found that the course of disease and the occurrence and development of UC might affect the occurrence of colon cancer through a systematic review of articles. UC was one of the risk factors of colorectal cancer.

To examine the clinical significance of miR-125b in esophageal squamous cell carcinoma (ESCC) and to research the effect of miR-125b on the biological function of ESCC cells and the relevant underlying mechanism.

The expression of miR-125b in ESCC tissues and cell lines were discovered by RT-PCR assay. The interrelation between miR-125b expression and clinicopathological parameters and the forecasting of ESCC patients were analyzed. CCK-8 method and Transwell methods were used to detect the increased growth, shifting, and irruption of ESCC cells. Bioinformatics analysis was applied to forecast the possible target genes of miR-125b and verified through dual-luciferase reporter gene assay. After that, the expression of p38-MAPK mRNA and protein were found out by RT-PCR and Western blot.

The expression of miR-125b was down-regulated in ESCC tissues and cell lines (P<0.05). And the expression of miR-125b was closely about tumor differentiation, TNM level, and lymph node metastasis in ESCC patients. The low miR-125b formulation was closely related to rough forecasting in ESCC patients. Large scale expression of miR-125b can effectively decrease the acceleration, shifting, and irrupting strengths of ESCC cells. Bioinformatics analysis showed p38-MAPK was forecasted to be a potential mark of miR-125b, which was confirmed by dual luciferase assay, and extreme expression of miR-125b can stop the expression of p38-MAPK mRNA and protein.

miR-125b is down-regulated in ESCC. Moreover, its expression level is significant concerning tumor progression and prognosis in patients with ESCC. MiR-125b can stop the high growth and shifting of ESCC cells having p38-MAPK at target.

Ulcerative colitis (UC) is a risk factor for carcinogenesis of colorectal cancer, which is associated with disruption of the epithelial barrier and disorder of the inflammatory response. It has been reported that the expression of microRNA (miR)-215 is upregulated in patients with long-term UC. The present study aimed to investigate the effects of miR-215 on lipopolysaccharide (LPS)-induced inflammatory injury in CCD-18Co cells, as well as to identify the underlying possible molecular mechanisms. CCD-18Co cells were treated with 1 µg/ml LPS to induce inflammatory injury. Reverse transcription-quantitative PCR was performed to determine the expression of miR-215 in LPS-treated CCD-18Co cells. Moreover, a dual luciferase reporter system assay was used to evaluate the interaction of miR-215 and growth differentiation factor 11 (GDF11) in CCD-18Co cells. The expression of miR-215 was significantly upregulated in LPS-treated CCD-18Co cells. Knockdown of miR-215 significantly alleviated the inflammatory response and oxidative stress in LPS-treated CCD-18Co cells. In addition, GDF11 was identified as a direct binding target of miR-215 in CCD-18Co cells. Knockdown of miR-215 significantly increased the expression of GDF11, but decreased the expression levels of Toll-like receptor (TLR)4, phosphorylated (p)-p65, iNOS, p-p38 and p-JNK in LPS-treated CCD-18Co cells. Collectively, the present findings indicated that knockdown of miR-215 alleviated oxidative stress and inflammatory response in LPS-treated CCD-18Co cells by upregulating GDF11 expression and inactivating the TLR4/NF-κB and JNK/p38 signaling pathways.

Introduction: Colon carcinoma is a common malignant tumor worldwide. Accurately predicting prognosis of colon adenocarcinoma (CA) patients may facilitate clinical individual decision-making. Many studies have reported that microRNAs (miRNAs) were associated with prognosis for patients with colon carcinoma. This study aimed to identify the prognosis-related miRNAs for predicting the overall survival (OS) of CA patients. Methods: Firstly, we analyzed the CA datasets from the Cancer Genome Atlas (TCGA), and looked for the prognosis-related miRNAs. Then, we developed a novel prediction model based on these miRNAs and the clinical characteristics. Time-dependent receiver operating characteristics (ROC) curves and calibration plots were used to evaluate the discrimination and accuracy of the signature and model. Finally, cell function assays and bioinformatics analyses were performed to evaluate the role of these selected miRNAs in modulating biological process in CA. Results: Six prognosis-related miRNAs were included in the miRNA-based signature, and it could effectively distinguish low-risk patients and high-risk patients. Furthermore, we established a prognostic model incorporating the six-miRNA-based signature and clinical characteristics. Areas under curves (AUCs) indicated that the six-miRNA-based model has a better predictive ability than TNM stage (AUC: 0.805 vs. 0.694). The calibration plots suggested close agreement between model predictions and actual observations. GO analysis showed that the target genes of these miRNAs are mainly involved in enrichment in protein binding and regulation of transcript and cytosol. KEGG pathway enrichment analysis indicated that these genes were mainly enriched in PI3K-Akt signaling pathway. Finally, we found that the five miRNAs except miR-152 were upregulated in tumor tissues and CA cells. The functional experiments revealed that miR-1245a, miR-3682, miR-33b, and miR-5683 promoted the migratory abilities and proliferation of CA cell, whereas miR-152 showed opposite effects. However, miR-4444-2 did not influence the migratory ability and proliferation of CA cell. Conclusions: In conclusion, we developed a novel six-miRNA-based model to predict 5-year survival probabilities for CA patients. This model has the potential to facilitate individualized treatment decisions.

Sirtuin 6 (Sirt6) is predominantly expressed in epithelial cells in intestinal crypts. It plays an important role in protecting intestinal epithelial cells against inflammatory injury. Previously, we found that colitis is associated with the downregulation of Sirt6 protein in the intestines. Here, we report that murine interferon-γ (Ifnγ) inhibits Sirt6 protein but not mRNA expression in young adult mouse colonocytes (YAMC, a mouse colonic epithelial cell line) in a dose- and time-dependent manner. Using microRNA array analysis, we showed that Ifnγ induces expression of miR-92b in YAMC cells. With in silico analysis, we found that the Sirt6 3'-untranslated region (UTR) contains a putative binding site for miR-92b. Luciferase assay showed that Ifnγ inhibited Sirt6 3'-UTR activity and this effect was mimicked by miR-92b via directly targeting the miR-92b seed site in the 3'-UTR of Sirt6 mRNA. Furthermore, Western blot demonstrated that miR-92b downregulated Sirt6 protein expression in YAMC cells. Blocking miR-92b with a specific inhibitor attenuated the inhibitory effect of Ifnγ on Sirt6 protein expression in the cells. Collectively, our data suggest that Ifnγ inhibits Sirt6 protein expression in intestinal epithelial cells via a miR-92b-mediated mechanism. miR-92b may be a novel therapeutic target for rescuing Sirt6 protein levels in intestinal epithelial cells, thereby protecting against intestinal mucosal injury caused by inflammation.