Recently, the long non-coding RNA (lncRNA) H19 has been identified as an oncogenic gene in multiple cancer types and elevated expression of H19 was tightly linked to tumorigenesis and cancer progression. However, the molecular basis for this observation has not been characterized in colorectal cancer (CRC) especially during epithelial to mesenchymal transition (EMT) progression. In our studies, H19 was characterized as a novel regulator of EMT in CRC. We found that H19 was highly expressed in mesenchymal-like cancer cells and primary CRC tissues. Stable expression of H19 significantly promotes EMT progression and accelerates in vivo and in vitro tumor growth. Furthermore, by using bioinformatics study and RNA immunoprecipitation combined with luciferase reporter assays, we demonstrated that H19 functioned as a competing endogenous RNA (ceRNA) for miR-138 and miR-200a, antagonized their functions and led to the de-repression of their endogenous targets Vimentin, ZEB1, and ZEB2, all of which were core marker genes for mesenchymal cells. Taken together, these observations imply that the lncRNA H19 modulated the expression of multiple genes involved in EMT by acting as a competing endogenous RNA, which may build up the missing link between the regulatory miRNA network and EMT progression.

Background The effect of Helicobacter pylori (H. pylori) eradication on gastric cancer (GC) prevention is controversial. Intestinal metaplasia (IM) seems to be a ''point of no return'' in the precancerous cascade. We performed a meta-analysis of randomized controlled trials (RCTs) to illustrate this issue. Materials and Methods The MEDLINE, EMBASE, Cochrane Library were searched for relevant RCTs that were published in any language up to March 2014. By dividing participants into subgroups based on their baseline diagnoses as group \IM (normal, non-atrophic gastritis, atrophic gastritis) and group CIM(intestinal metaplasia, dysplasia), the relative risk (RR) of GC in each study compared treatment group with control group were pooled using Mantel-Haenszel fixed-effect model and publication bias analyses were performed.Results Ten studies from eight RCTs were included in this analysis, for a total of 7,955 participants. H. pylori treatment compared with control significantly reduced the risk of GC, with a pooled RR of 0.64 (95 % CI, 0.48-0.85). Subgroup analysis for patients with non-atrophic gastritis, atrophic gastritis (\IM) yielded a similar results (RR = 0.25, 95 % CI, 0.08-0.81). But this difference was not observed in patients with intestinal metaplasia, dysplasia (CIM) (RR = 0.88; 95 % CI, 0.59-1.31). Conclusions Our results suggested that patients with Intestinal metaplasia or dysplasia could not benefit from the H. pylori treatment on the risk of GC.

NLRP3 inflammasome is a key multiprotein signaling platform that tightly controls inflammatory responses and coordinates antimicrobial host defenses by activating caspase-1 for the subsequent maturation of pro-inflammatory cytokines, IL-1β and IL-18, and induces pyroptosis. The assembly and activation of NLRP3 inflammasome are linked to the pathogenesis of several cardiovascular disease risk factors, such as hypertension and diabetes, and their major consequences-myocardial remodeling. The study of the NLRP3 inflammasome in these cardiovascular disease states may uncover important triggers and endogenous modulators of the disease, and lead to new treatment strategies. This review outlines current insights into NLRP3 inflammasome research associated with cardiovascular diseases and discusses the questions that remain in this field.

Rationale: Pyroptosis is a morphologically and mechanistically distinct form of cell death and is characterized by gasdermin D (GSDMD) or gasdermin E (GSDME)-mediated necrosis with excessive inflammatory factor release. Cardiomyocyte necrosis and inflammation play key roles in the pathophysiology of myocardial ischemia/reperfusion (I/R) injury. However, whether cardiomyocytes undergo pyroptosis and the underlying mechanism in myocardial I/R injury remain unclear. Objective: We aimed to investigate the role of pyroptosis in myocardial I/R injury. Methods and Results: In vivo and in vitro experiments were used to investigate pyroptosis of cardiomyocyte and the associated mechanisms during I/R injury. Wild-type (WT), Myh6-Cre and cardiomyocyte-specific GSDMD-deficient (GSDMD-CKO) male mice were subjected to I/R. Human peripheral blood samples were collected from STEMI (acute ST-segment-elevation myocardial infarction) patients or control patients at 0, 1 and 24 h after PCI (percutaneous coronary intervention) in our department. The serum levels of GSDMD were measured by ELISA. H/R (hypoxia/reoxygenation) induced cardiomyocyte pyroptosis and the release of mature IL-18 but not IL-1β, which mechanistically resulted from GSDMD cleavage by caspase-11 in cardiomyocytes. Furthermore, GSDMD gene deletion blocked H/R-induced cardiomyocyte pyroptosis and IL-18 release. GSDMD and its pyroptosis-inducing N-terminal fragment (GSDMD-N) were upregulated in myocardial tissues after I/R injury. Immunofluorescence analysis showed that GSDMD was mainly localized in cardiomyocytes. GSDMD deficiency in cardiomyocytes significantly reduced the I/R-induced myocardial infarct size. Moreover, increased GSDMD serum levels were detected in patients exhibiting I/R injury 1 h after PCI for STEMI. Conclusions: Our results show that GSDMD-mediated cardiomyocyte pyroptosis is a key event during myocardial I/R injury and that the caspase-11/GSDMD pathway may be essential to this process. Additionally, GSDMD inhibition significantly reduces cardiomyocyte pyroptosis and I/R-induced myocardial injury.