Ginsenoside Rg3 Ameliorates DSS-Induced Colitis by Inhibiting NLRP3 Inflammasome Activation and Regulating Microbial Homeostasis.

Ulcerative colitis (UC) is a recurrent inflammatory disease without a specific cure or treatment for improvement. Here, we investigated the potential therapeutic effect and mechanism of ginsenoside Rg3 (Gin Rg3) on UC. We constructed an in vitro cellular inflammatory model and a dextran sulfate sodium (DSS)-induced UC mouse model. We also used Gin Rg3, MCC950 (NLRP3 inhibitor), MSU (NLRP3 activator), and fecal transplantation (FMT) to intervene the model. The results showed that Gin Rg3 inhibited NLRP3 inflammasome activation, pyroptosis, and apoptosis in vitro and in vivo. DSS-induced changes in the abundance of gut microbiota at the phylum or genus level were partially restored by Gin Rg3. Furthermore, gin Rg3 affected intestinal metabolism in mice by inhibiting the activation of NLRP3 inflammasome. The gut microbiota treated with Gin Rg3 was sufficient to alleviate DSS-induced UC. In summary, Gin Rg3 alleviated DSS-induced UC by inhibiting NLRP3 inflammasome activation and regulating gut microbiota homeostasis.

CXCR4/TGF-ß1 mediated self-differentiation of human mesenchymal stem cells to carcinoma-associated fibroblasts and promoted colorectal carcinoma development.

Background: Tumor microenvironment (TME) is a crucial part of tumor hallmarks. Mesenchymal stem cells (MSCs), important components of TME, are the main source of Carcinoma-associated fibroblasts (CAFs), but the mechanism of transformation regulation is still unclear. Transforming growth factor-ß1 (TGF-ß1), chemokine Stromal cell-derived factor-1 (SDF-1) and its endogenous receptor CXCR4 may play important roles during this process.Methods: Co-culture technique was used to explore the effects of MSCs on the proliferation, migration and invasion of colorectal carcinoma (CRC) cells and how they induced MSCs to differentiate into CAFs. The expression of α-SMA, Vimentin, S100A4 and FAP were detected as CAFs markers. Inhibitors AMD3100 and cyclophosphamide (Cy) were pre-treated in MSCs to verify the functions of CXCR4/TGF-ß1. Finally, the xenograft models in nude mice were generated to further verify this process in vivo.Results: MSCs promoted the CRCs proliferation, invasion and migration, and induced SDF-1 expression and secretion, which dramatically up-regulated CXCR4 and TGF-ß1 expression in MSCs. The levels of CAFs markers elevated in MSCs, indicating CAFs differentiation occurred in MSCs. AMD3100 and Cy treatment significantly blocked this differentiation process of MSCs by suppressing CXCR4 expression and TGF-ß1 secretion. In vivo xenograft experiments also demonstrated that MSCs promoted differentiation into CAFs through CXCR4/TGF-ß1 signaling in either primary tumor tissues or hepatic metastatic tissues of CRC.Conclusion: Our studies have revealed the essential role of CXCR4/TGF-ß1 axis playing in the transformation of tumor microenvironment by mediating MSCs differentiation into CAFs, promoting CRCs growth and metastasis.

Knockdown of lncRNA CCEPR suppresses colorectal cancer progression.

Long non-coding RNAs (lncRNAs) serve important roles in colorectal cancer. The aim of the present study was to investigate the expression and role of cervical carcinoma expressed PCNA regulatory (CCEPR) lncRNA in colorectal cancer progression. The results demonstrated that CCEPR expression was significantly higher in colorectal cancer tissues when compared with paired adjacent normal tissues. In addition, CCEPR expression was significantly higher in patients with advanced colorectal cancer (stage III/IV) than those with early-stage colorectal cancer (stage I/II). High CCEPR expression was significantly associated with poor differentiation, advanced clinical stage, positive lymph node metastasis and distant metastasis. Of particular note, patients with colorectal cancer exhibiting high CCEPR expression levels had shorter survival rates when compared with patients with low CCEPR expression. In vitro experiments demonstrated that the expression of CCEPR was increased in colorectal cancer cell lines when compared with a normal colon cell line. Knockdown of CCEPR significantly inhibited colorectal cancer cell proliferation, colony formation and cell cycle progression, as well as cell migration and invasion. Finally, silencing of CCEPR downregulated matrix metalloproteinase (MMP)-2 and MMP-9 expression and suppressed epithelial-mesenchymal transition in colorectal cancer cells. In conclusion, the results of the present study suggest that CCEPR may exert an oncogenic role in colorectal cancer, and CCEPR may be a promising molecular target for colorectal cancer treatment.

Positive expression of basic transcription factor 3 predicts poor survival of colorectal cancer patients: possible mechanisms involved.

Basic transcription factor 3 (BTF3) is associated with the development of several cancers. The aim of our study was to elucidate the role of BTF3 in colorectal cancer (CRC) tissues. CRC tissues or their paired adjacent noncancerous (ANCT) tissues were obtained from 90 patients who underwent operations in our hospital from November 2011 to December 2016, and then we implemented a gene microarray assay for detecting significant changes in gene expression and confirmed expression in tissues using immunohistochemistry and real-time PCR. We transfected or injected the silencing BTF3 (BTF3-siRNA) plasmid into cells and nude mice, and measured the tumorigenicity of CRC cells with flow cytometry and studied the expression level of BTF3 downstream genes (MAD2L2, MCM3 and PLK1) in CRC cells. BTF3 expression level was not only significantly higher in CRC tissue than in ANCT tissue (2.61 ± 0.07 vs 1.90 ± 0.03, P < 0.001) but BTF3-siRNA decreased tumor formation in a nude mice model. Furthermore, based on the data of gene microarray analysis, MAD2L2, MCM3 and PLK1 were detected as the downstream target genes of BTF3 and their expressions were positive related with BTF3 expression. Also, through transfecting BTF3-siRNA into HCT116 cells, we found that BTF3-siRNA could decrease cell viability and induced cell apoptosis and blocking the cell cycle. In conclusion, BTF3 is positively related to CRC and BTF3-siRNA attenuated the tumorigenicity of colorectal cancer cells via MAD2L2, MCM3 and PLK1 activity reduction.

lncRNA B4GALT1-AS1 promotes colon cancer cell stemness and migration by recruiting YAP to the nucleus and enhancing YAP transcriptional activity.

Here, an RNA-sequencing assay revealed long noncoding RNAs (lncRNAs) with an ectopic expression between colon cancer (CC) and normal colon epithelial cells, in which lncRNA B4GALT1-AS1 exhibited the highest change. A 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay indicated that B4GALT1-AS1 knockdown had no effect on CC cell viability, however, cell clone formation analysis showed that B4GALT1-AS1 knockdown attenuated the capacity of cell clone formation. Additionally, gene set enrichment analysis of this data set revealed that positive enrichment of stem cell-differentiated signatures and negative embryonic stem cell function and adult tissue stem module were observed in CC cells with B4GALT1-AS1 knockdown. Furthermore, B4GALT1-AS1 knockdown suppressed the stemness-marker expression, the ability of cell spheroid formation, and ALDH1 activity in CC cells. Mechanistically, RNA-sequencing data found that the Hippo pathway in cancer was shown on pathways mostly upregulated by B4GALT1-AS1 knockdown, and B4GALT1-AS1 directly bound to the yes-associated protein (YAP), a downstream executor of the Hippo pathway, and B4GALT1-AS1 knockdown promoted the nuclear cytoplasm translocation of YAP and decreased YAP transcriptional activity. Notably, YAP overexpression attenuated the inhibitory effects mediated by B4GALT1-AS1 knockdown. Our results identify the direct binding of lncRNA B4GALT1-AS1 to YAP, which is responsible for CC cell stemness.

Imaging Kayser-Fleischer Ring in Wilson Disease Using In Vivo Confocal Microscopy.

PURPOSE: This study analyzes images of Kayser-Fleischer (K-F) rings in patients with Wilson disease (WD) using in vivo confocal microscopy (IVCM) and explores whether IVCM can be a useful clinical tool in facilitating the diagnosis and characterization of K-F rings. METHODS: One hundred four eyes of 52 patients with WD and K-F rings (K-F group) and 52 normal eyes of 52 age- and gender-matched control subjects (control group) were enrolled in the study. Both K-F and control groups consisted of 29 male patients and 23 female patients. IVCM imaging was performed, and images of the peripheral Descemet membrane were analyzed. RESULTS: All patients in K-F group showed abnormal patterns in the peripheral Descemet membrane from IVCM images. These abnormalities can be generally divided into 3 types: patchy, stripy, and spotty patterns. Each patient may have a combination of these patterns, with patchy pattern being most prevalent (100%), whereas stripy and spotty patterns are present in 30% to 40% of the K-F rings. Notably, these patterns are not correlated with other systematic symptoms of WD. CONCLUSIONS: IVCM images can be used as an objective clinical diagnostic tool to facilitate the identification of K-F rings and the diagnosis of WD.

LncRNA HOTAIR is a Prognostic Biomarker for the Proliferation and Chemoresistance of Colorectal Cancer via MiR-203a-3p-Mediated Wnt/ß-Catenin Signaling Pathway.

BACKGROUND/AIMS: HOX transcript antisense RNA (HOTAIR) plays a vital role in carcinogenesis. However, its functional and regulatory roles remain unclear. In this study, we aimed to investigate its biological function and clinical significance in human colorectal cancer (CRC). METHODS: We examined the expression levels of lncRNA HOTAIR and miR-203a-3p in CRC tissues and CRC cell lines by qRT-PCR. Gain and loss-of-function assays were performed to examine the effects of HOTAIR and miR-203a-3p on the proliferation and chemoresistance of CRC cells. The possible mechanisms of HOTAIR were also explored by fluorescence reporter assay and Western blot. RESULTS: The expressions of HOTAIR were upregulated in CRC tissue tissues compared to adjacent control tissues. We also found HOTAIR was downregulated by miR-203a-3p in CRC cell lines. Both HOTAIR knockdown and miR-203a-3p overexpression in CRC cell lines led to inhibited cell proliferation and reduced chemoresistance. We also determined that ß-catenin and GRG5 were inhibitory targets of miR-203a-3p, and that Wnt/ß-catenin signaling was inhibited by both HOTAIR knockdown and miR-203a-3p overexpression. Significantly, we found that increased expression of miR-203a-3p is essential for cell proliferation repression, chemoresistance reduction, and Wnt/ß-catenin signaling inhibition induced by HOTAIR knockdown. CONCLUSIONS: Our study demonstrated that the lncRNA HOTAIR could regulate the progression and chemoresistance of CRC via modulating the expression levels of miR-203a-3p and the activity of Wnt/ß-catenin signaling pathway.

[Multidisciplinary-team approach in diagnosis and treatment of patients with chronic constipation].

Chronic constipation is one of the common diseases in clinic. For the complicated causes and pathophysiology, the overall efficacy is not satisfactory in the traditional medical model. Multidisciplinary-team (MDT) approach is a new team medical model, which is also an important systematic and modular medical approach. Treating patients with chronic constipation by multidisciplinary-team approach is an effective way to improve the overall efficacy. In diagnosis, MDT approach can get more accurate and explicit diagnosis and type of the constipation by gathering patients' detailed medical history, complete physical examination, laboratory and image test, patients' mental and nutritional condition. In treatment, MDT members can cooperate in various fields, such as basic research, medicine, physics, psychology, surgery and conversion therapy, and that may provides more thoughts and methods for the treatment of chronic constipation.

Biologic mesh versus synthetic mesh in open inguinal hernia repair: system review and meta-analysis.

BACKGROUND: Biologic meshes are mostly used for abdominal wall reinforcement in infected fields, but no consensus has been reached on its use for inguinal hernia repairing. The purpose of this study was to compare biologic mesh with synthetic mesh in open inguinal herniorrhaphy. METHODS: A systematic literature review and meta-analysis was undertaken to identify studies comparing the outcomes of biologic mesh and synthetic mesh in open inguinal hernia repair. Published studies were identified by the databases PubMed, EMBASE and the Cochrane Library. RESULTS: A total of 382 patients in five randomized controlled trials were reviewed (179 patients in biologic mesh group; 203 patients in synthetic mesh group). The two groups did not significantly differ in chronic groin pain (P = 0.06) or recurrence (P = 0.38). The incidence of seroma trended higher in biologic mesh group (P = 0.03). Operating time was significantly longer with biologic mesh (P = 0.03). There was no significant difference in hematomas (P = 0.23) between the two groups. CONCLUSIONS: From the data of this study, biologic mesh had no superiority to synthetic mesh in open inguinal hernia repair with similar recurrence rates and incidence of chronic groin pain, but higher rate of seroma and longer operating time. However, this mesh still needs to be assessed in a large, multicentre, well-designed randomized controlled trial.

Self-gripping mesh versus sutured mesh in open inguinal hernia repair: system review and meta-analysis.

BACKGROUND: The objective of this article was to compare the outcomes of self-gripping mesh (GM) with sutured mesh (SM) in open inguinal hernia repair. METHODS: A systematic review and meta-analysis were taken to compare the outcomes of GM and SM in open inguinal hernia repair. RESULTS: A total of 1,353 patients in 6 randomized controlled trials and 2 observational studies were reviewed (666 patients in GM group; 687 patients in SM group). The 2 groups did not significantly differ in chronic groin pain (P = .23) or recurrence (P = .59). The operating time was significantly shorter in GM group (P < .00001). There was no significant difference in infection (P = .18), seromas (P = .35), hematomas (P = .87), or discomfort (P = .58) between the 2 groups. CONCLUSIONS: The data showed that GM was equivalent to SM in open inguinal hernia repair. However, this new mesh still needs to be confirmed in large, multi-center, well-designed randomized controlled trials.