Nononcogenic restoration of the intestinal barrier by E. coli-delivered human EGF.

Although mucoactive proteins, such as epidermal growth factor (EGF), could improve clinical outcomes of intestinal ulcerative diseases, their gastrointestinal application is limited because of their proteolytic digestion or concerns about tumor promotion. In the present study, ATP-binding cassette (ABC) transporter-linked secretion of human EGF from probiotic Escherichia coli (EGF-EcN) was created to promote beneficial actions of the EGF receptor, which is notably attenuated in patients with intestinal ulcerative injuries. Preventive and postinjury treatment with EGF-EcN alleviated intestinal ulcers and other readouts of disease severity in murine intestinal ulcer models.

C/EBP homologous protein promotes NSAID-activated gene 1-linked pro-inflammatory signals and enterocyte invasion by enteropathogenic Escherichia coli.

NSAID-activated Gene 1 (NAG-1) is a prognostic indicator of chronic inflammatory diseases and aggressive tumors. Among the stress sentinels in response to infection by enteropathogenic Escherichia coli (EPEC) or other pathogenic E. coli, C/EBP homologous protein (CHOP), a representative stress-regulated transcription factor, was prominently increased and assessed for its involvement in NAG-1-mediated pathogenic cellular responses.

Identification and molecular characterization of cellular factors required for glucocorticoid receptor-mediated mRNA decay.

Glucocorticoid (GC) receptor (GR) has been shown recently to bind a subset of mRNAs and elicit rapid mRNA degradation. However, the molecular details of GR-mediated mRNA decay (GMD) remain unclear. Here, we demonstrate that GMD triggers rapid degradation of target mRNAs in a translation-independent and exon junction complex-independent manner, confirming that GMD is mechanistically distinct from nonsense-mediated mRNA decay (NMD).

Epithelial Cholesterol Deficiency Attenuates Human Antigen R-linked Pro-inflammatory Stimulation via an SREBP2-linked Circuit.

Patients with chronic intestinal ulcerative diseases, such as inflammatory bowel disease, tend to exhibit abnormal lipid profiles, which may affect the gut epithelial integrity. We hypothesized that epithelial cholesterol depletion may trigger inflammation-checking machinery via cholesterol sentinel signaling molecules whose disruption in patients may aggravate inflammation and disease progression. In the present study, sterol regulatory element-binding protein 2 (SREBP2) as the cholesterol sentinel was assessed for its involvement in the epithelial inflammatory responses in cholesterol-depleted enterocytes.

Early Epithelial Restitution by Nonsteroidal Anti-Inflammatory Drug-Activated Gene 1 Counteracts Intestinal Ulcerative Injuries.

In response to ulcerative mucosal injuries, intestinal epithelial restitution is a critical event in the early defense against harmful attacks by luminal Ags. Based on the assumption that epithelial NAG-1 is an endogenous regulator of ulcerative stress-induced injuries, the expression and functions of NAG-1 were investigated. Genetic ablation of NAG-1 decreased survival of mice with dextran sodium sulfate-induced intestinal ulcer and histologically delayed the epithelial restitution, confirming early protective roles of NAG-1 in ulcerative insults.

Ribosome Inactivation Leads to Attenuation of Intestinal Polymeric Ig Receptor Expression via Differential Regulation of Human Antigen R.

The polymeric IgR (pIgR) is a central component in the transport of IgA across enterocytes and thereby plays a crucial role in the defense against enteropathogens and in the regulation of circulating IgA levels. The present study was performed to address the novel regulation of pIgR expression in intestinal epithelia undergoing ribosome inactivation. Insults to mucosa that led to ribosome inactivation attenuated pIgR expression in enterocytes.

Curcumin mitigates accelerated aging after irradiation in Drosophila by reducing oxidative stress.

Curcumin, belonging to a class of natural phenol compounds, has been extensively studied due to its antioxidative, anticancer, anti-inflammatory, and antineurodegenerative effects. Recently, it has been shown to exert dual activities after irradiation, radioprotection, and radiosensitization. Here, we investigated the protective effect of curcumin against radiation damage using D.

Reactive oxygen species-regulated signaling pathways in diabetic nephropathy.

Diabetic nephropathy is characterized by excessive deposition of extracellular matrix (ECM) in the kidney. TGF-beta1 has been identified as the key mediator of ECM accumulation in diabetic kidney. High glucose induces TGF-beta1 in glomerular mesangial and tubular epithelial cells and in diabetic kidney.