Membrane repair against H. pylori promotes cancer cell proliferation

Membrane repair is a universal response against physical and biological insults and enables cell survival. Helicobacter pylori is one of the most common human pathogens and the first formally recognized bacterial carcinogen associated with gastric cancer. However, little is known about host membrane repair in the context of H. pylori infection. Here we show that H. pylori disrupts the host plasma membrane and induces Ca2+ influx, which triggers the translocation of annexin family members A1 and A4 to the plasma membrane. This in turn activates a membrane repair response through the recruitment of lysosomal membranes and the induction of downstream signaling transduction pathways that promote cell survival and proliferation. Based on our data, we propose a new model by which H. pylori infection activates annexin A1 and A4 for membrane repair and how annexin A4 over-expression induced signaling promotes cell proliferation. Continual activation of this membrane repair response signaling cascade may cause abnormal cellular states leading to carcinogenesis. This study links H. pylori infection to membrane repair, providing insight into potential mechanisms of carcinogenesis resulting from membrane damage

Integrative network analysis reveals active microRNAs and their functions in gastric cancer

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) are a class of endogenous, small and highly conserved noncoding RNAs that control gene expression either by degradation of target mRNAs or by inhibition of protein translation. They play important roles in cancer progression. A single miRNA can provoke a chain reaction and further affect protein interaction network (PIN). Therefore, we developed a novel integrative approach to identify the functional roles and the regulated PIN of oncomirs.</p> <p>Results</p> <p>We integrated the expression profiles of miRNA and mRNA with the human PIN to reveal miRNA-regulated PIN in specific biological conditions. The potential functions of miRNAs were determined by functional enrichment analysis and the activities of miRNA-regulated PINs were evaluated by the co-expression of protein-protein interactions (PPIs). The function of a specific miRNA, miR-148a, was further examined by clinical data analysis and cell-based experiments. We uncovered several miRNA-regulated networks which were enriched with functions related to cancer progression. One miRNA, miR-148a, was identified and its function is to decrease tumor proliferation and metastasis through its regulated PIN. Furthermore, we found that miR-148a could reduce the invasiveness, migratory and adhesive activities of gastric tumor cells. Most importantly, elevated miR-148a level in gastric cancer tissues was strongly correlated with distant metastasis, organ and peritoneal invasion and reduced survival rate.</p> <p>Conclusions</p> <p>This study provides a novel method to identify active oncomirs and their potential functions in gastric cancer progression. The present data suggest that miR-148a could be a potential prognostic biomarker of gastric cancer and function as a tumor suppressor through repressing the activity of its regulated PIN.</p

Effects of a Modified Hospital Elder Life Program on Frailty in Individuals Undergoing Major Elective Abdominal Surgery

Objectives To test the effects of a modified Hospital Elder Life Program (mHELP) on frailty. Design Matched and unmatched analyses of data from a before-and-after study. Setting Hospital, inpatient. Participants Participants aged 65 years and older ((N = 189) undergoing elective, major abdominal surgery at a medical center in Taiwan. Intervention The mHELP included three nursing interventions: early mobilization, oral and nutritional assistance, and orienting communication. Measurements Frailty rate and transitions between frailty states from hospital discharge to 3 months after discharge, using Fried's phenotype criteria categorized as: non-frail (0 or 1 criteria present), pre-frail (2 or 3 criteria present), and frail (4 or 5 criteria present). Results Among matched pairs, participants who received the mHELP interventions were significantly less likely to be frail at discharge (19.2% vs. 65.4% for controls; adjusted OR = .10, 95% CI = .02 to .39) than their matched controls. Transitions to states of greater frailty during hospitalization were more common for participants in the control group. At 3 months post-discharge, participants who received the mHELP intervention during hospitalization were less likely to be frail than the matched controls (17.3% versus 23.1%; adjusted OR = .73; 95% CI = .21 to 2.56), although this difference did not achieve statistical significance. Conclusion The mHELP intervention is effective in reducing frailty by hospital discharge but the benefit is diminished by 3 months post-discharge. Thus, the mHELP provides a useful approach to manage in-hospital frailty for older patients undergoing major abdominal surgery

Major Functional Transcriptome of an Inferred Center Regulator of an ER(−) Breast Cancer Model System

We aimed to find clinically relevant gene activities ruled by the signal transducer and activator of transcription 3 (STAT3) proteins in an ER(−) breast cancer population via network approach. STAT3 is negatively associated with both lymph nodal category and stage. MYC is a component of STAT3 network. MYC and STAT3 may co-regulate gene expressions for Warburg effect, stem cell like phenotype, cell proliferation and angiogenesis. We identified a STAT3 network in silico showing its ability in predicting its target gene expressions primarily for specific tumor subtype, tumor progression, treatment options and prognostic features. The aberrant expressions of MYC and STAT3 are enriched in triple negatives (TN). They promote histological grade, vascularity, metastasis and tumor anti-apoptotic activities. VEGFA, STAT3, FOXM1 and METAP2 are druggable targets. High levels of METAP2, MMP7, IGF2 and IGF2R are unfavorable prognostic factors. STAT3 is an inferred center regulator at early cancer development predominantly in TN