Identification of Two Novel Circular RNAs Deriving from BCL2L12 and Investigation of Their Potential Value as a Molecular Signature in Colorectal Cancer

The utility of circular RNAs (circRNAs) as molecular biomarkers has recently emerged. However, only a handful of them have already been studied in colorectal cancer (CRC). The purpose of this study was to identify new circRNAs deriving from BCL2L12, a member of the BCL2 apoptosis-related family, and investigate their potential as biomarkers in CRC. Total RNA extracts from CRC cell lines and tissue samples were reversely transcribed. By combining PCR with divergent primers and nested PCR followed by Sanger sequencing, we were able to discover two BCL2L12 circRNAs. Subsequently, bioinformatical tools were used to predict the interactions of these circRNAs with microRNAs (miRNAs) and RNA-binding proteins (RBPs). Following a PCR-based pre-amplification, real-time qPCR was carried out for the quantification of each circRNA in CRC samples and cell lines. Biostatistical analysis was used to assess their potential prognostic value in CRC. Both novel BCL2L12 circRNAs likely interact with particular miRNAs and RBPs. Interestingly, circ-BCL2L12-2 expression is inversely associated with TNM stage, while circ-BCL2L12-1 overexpression is associated with shorter overall survival in CRC, particularly among TNM stage II patients. Overall, we identified two novel BCL2L12 circRNAs, one of which can further stratify TNM stage II patients into two subgroups with substantially distinct prognosis.     

The Intestinal Barrier and Its Dysfunction in Patients with Metabolic Diseases and Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) represents an increasing cause of liver disease worldwide, mirroring the epidemics of obesity and metabolic syndrome. As there are still no licensed medications for treating the disease, there is an ongoing effort to elucidate the pathophysiology and to discover new treatment pathways. An increasing body of evidence has demonstrated a crosstalk between the gut and the liver, which plays a crucial role in the development and progression of liver disease. Among other intestinal factors, gut permeability represents an interesting factor at the interface of the gut–liver axis. In this narrative review, we summarise the evidence from human studies showing the association between increased gut permeability and NAFLD, as well as with type-2 diabetes and obesity. We also discuss the manipulation of the gut permeability as a potential therapeutical target in patients with NAFLD.     

Oxidative stress due to anesthesia and surgical trauma: Importance of early enteral nutrition

Anesthesia and surgical trauma are considered major oxidative and nitrosative stress effectors resulting in the development of SIRS. In this study we evaluated the usefulness of early enteral nutrition after surgical trauma. Sixty male Wistar rats were subjected to midline laparotomy and feeding‐gastrostomy. Twenty of these rats served as controls after recovering from the operation stress. The remaining rats received, through gastrostomy, enteral nutrition or placebo‐feeding for 24 h. Oxidative stress markers and CC chemokine production were evaluated in rat serum and liver tissue. The operation itself was found to increase nitric oxide (NO) and malondialdehyde (MDA) and to decrease superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px), as well as liver tissue energy charge (EC) in relation to controls. The rats receiving enteral feeding exhibited statistically significantly lower levels of NO and MDA, and higher levels of SOD, GSH‐Px, and liver EC, in relation to placebo feeding rats. The operation significantly increased the chemokines monocyte chemoattractant protein (MCP)‐1 and regulated upon activation, normal T‐cell expressed, and secreted (RANTES) in rat serum, while enteral nutrition caused a further significant increase in chemokine levels in serum. mRNA chemokine expression in liver was increased in a similar pattern. These findings indicate that early enteral feeding might play an important role after surgery ameliorating oxidative stress, affecting positively the hepatic EC and regulating, via chemokine production, cell trafficking, and healing process.