-Cardiac dysfunction is a major component of sepsis-induced multi-organ failure in critical care units. Changes in cardiac autophagy and its role during sepsis pathogenesis have not been clearly defined. Targeted autophagy-based therapeutic approaches for sepsis are not yet developed. -Beclin-1-dependent autophagy in the heart during sepsis and the potential therapeutic benefit of targeting this pathway were investigated in a mouse model of lipopolysaccharide (LPS)-induced sepsis. -LPS induced a dose-dependent increase in autophagy at low doses, followed by a decline that was in conjunction with mTOR activation at high doses. Cardiac-specific overexpression of Beclin-1 promoted autophagy, suppressed mTOR signaling, improved cardiac function, and alleviated inflammation and fibrosis after LPS challenge. Haplosufficiency for resulted in opposite effects. Beclin-1 also protected mitochondria, reduced the release of mitochondrial DAMPs, and promoted mitophagy via PINK1-Parkin but not adaptor proteins in response to LPS. Injection of a cell-permeable Tat-Beclin-1 peptide to activate autophagy improved cardiac function, attenuated inflammation, and rescued the phenotypes caused by deficiency in LPS-challenged mice. -These results suggest that Beclin-1 protects the heart during sepsis and that the targeted induction of Beclin-1 signaling may have important therapeutic potential.

We developed a nomogram prognostic model for SCLC patients, and validated the model using an independent patient cohort. The nomogram performs better than earlier models, including models using AJCC staging.

SignificanceApproximately 20% of breast cancers have amplification of a cancer-causing signaling molecule known as human epidermal growth factor receptor 2 (HER2). Decreased mRNA expression of the autophagy gene, beclin 1/BECN1, increases the risk of HER2-positive breast cancer. However, the role of Beclin 1-dependent autophagy in regulating HER2-mediated tumorigenesis is unknown. Here, we show that a mutation in Becn1 that increases basal autophagy prevents HER2-mediated tumorigenesis in mice and prevents HER2-mediated inhibition of autophagy in cultured cells. Furthermore, treatment with a cell-penetrating, autophagy-inducing peptide derived from Beclin 1 inhibits growth of HER2-positive human breast tumor xenografts in mice as efficiently as a clinically used agent that inhibits HER2 receptor tyrosine kinase activity. These findings demonstrate that genetic and pharmacological activation of autophagy inhibits HER2-mediated breast tumorigenesis.

We constructed a lung cancer-specific database housing expression data and clinical data from over 6700 patients in 56 studies. Expression data from 23 genome-wide platforms were carefully processed and quality controlled, whereas clinical data were standardized and rigorously curated. Empowered by this lung cancer database, we created an open access web resource—the Lung Cancer Explorer (LCE), which enables researchers and clinicians to explore these data and perform analyses. Users can perform meta-analyses on LCE to gain a quick overview of the results on tumor vs non-malignant tissue (normal) differential gene expression and expression-survival association. Individual dataset-based survival analysis, comparative analysis, and correlation analysis are also provided with flexible options to allow for customized analyses from the user.

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