Lung cancer is a malignancy with high morbidity and mortality worldwide. More evidences indicated that gut microbiome plays an important role in the carcinogenesis and progression of cancers by metabolism, inflammation and immune response. However, the study about the characterizations of gut microbiome in lung cancer is limited. In this study, the fecal samples were collected from 16 healthy individuals and 30 lung cancer patients who were divided into 3 groups based on different tumor biomarkers (cytokeratin 19 fragment, neuron specific enolase and carcinoembryonic antigen, respectively) and were analyzed using 16S rRNA gene amplicon sequencing. Each lung cancer group has characterized gut microbial community and presents an elimination, low-density, and loss of bacterial diversity microbial ecosystem compared to that of the healthy control. The microbiome structures in family and genera levels are more complex and significantly varied from each group presenting more different and special pathogen microbiome such as Enterobacteriaceae, Streptococcus, Prevotella, etc and fewer probiotic genera including Blautia, Coprococcus, Bifidobacterium and Lachnospiraceae. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and COG annotation demonstrated decreased abundance of some dominant metabolism-related pathways in the lung cancer. This study explores for the first time the features of gut microbiome in lung cancer patients and may provide new insight into the pathogenesis of lung cancer system, with the implication that gut microbiota may serve as a microbial marker and contribute to the derived metabolites, development and differentiation in lung cancer system.

Rational design of AAV capsids is a simple method for enhancing AAV transduction efficiency. AAV-DJ is a highly recombinogenic hybrid vector created from DNA shuffling of eight AAV serotypes, which mediates efficient gene expression both in vitro and in vivo. AAV2 and AAV8 are the closest parental vectors of AAV-DJ and it has been reported that mutations on the 137/251/503 ubiquitination or phosphorylation sites of the AAV2 or AAV8 capsid lead to dramatic enhancement of gene delivery. Here, we aimed to find out whether the same point mutations on the AAV-DJ capsid could lead to significant improvement for gene delivery both in vitro and in vivo. We constructed three single point mutants (K137R/T251A/S503A) of AAV-DJ and the transduction efficiency of these mutants and AAV-DJ were investigated using two reporter gene systems including green fluorescent protein (GFP) and dual-luciferase (Gaussia luciferase and Firefly luciferase). Data indicated that single point mutations T251A/S503A lead to significant improvement of dual-luciferase expression in vivo after tail vein (TV) injection in mice respectively, despite limited enhancement of GFP expression in 293 T, Hela and HepG2 cells in vitro. Moreover, in vivo bioluminescence image and viral genome DNA copy number in tissue analysis showed that these mutants reserved the liver tropism characteristics, consistent with AAV-DJ. Single point mutations on the 251/503 sites of AAV-DJ capsid can lead to a significant improvement for in vivo gene expression. These enhanced AAV vectors have great potential in gene therapy applications.

Endothelial dysfunction and excessively stimulated autophagy, often caused by oxidant injury or inflammation, will lead to atherosclerosis development and progression in diabetes. The aim of this study is to investigate the protective effect of glucagon-like peptide-1 (GLP-1) treatment on preventing oxidative stress-induced endothelial dysfunction and excessively stimulated autophagy. Treatment of endothelial cells with GLP-1 significantly attenuated oxidative stress-induced endothelial dysfunction and autophagy, which was associated with the reduction of intracellular reactive oxygen species (ROS) levels. These protective effects of GLP-1 were likely mediated by reducing phosphorylation of ERK1/2. We further demonstrated that GLP-1 treatment could reverse downregulation of epigenetic factor histone deacetylase 6 (HDAC6), a downstream molecular of the EKR1/2, induced by oxidant injury. In conclusion, our results suggest that GLP-1 produces a protective effect on endothelial cells from oxidant injury by preventing endothelial dysfunction and autophagy, which may be dependent on restoring HDAC6 through a GLP-1R-ERK1/2-dependent manner.

Objective: Apoptosis and autophagy of retinal cells, which may be induced by oxidative stress, are tightly associated with the pathogenesis of diabetic retinopathy (DR). The autophagy induced by oxidative stress is considered as excessively stimulated autophagy, which accelerates the progression of DR. This study aims to investigate the protective effect of GLP-1 treatment on alleviating apoptosis and autophagy of retinal cells in type 2 diabetic rats and reveals its possible mechanism.

Angiotensin II (Ang II) type 1 receptor blocking drugs have been shown to inhibit the growth of prostate cancer cells and delay the development of prostate cancer. Functional Ang II type 2 receptors (AT2R) are present in these cells and inhibit growth induced by epidermal growth factor. The present studies report apoptosis of prostate cancer cells induced by AT2R overexpression. A recombinant adenoviral vector expressing AT2R (Ad-G-AT2R-EGFP) was transduced into prostate cancer cells, including androgen-independent (DU145 and PC3) and androgen-dependent cell lines (LNCaP). Following AT2R transduction, apoptosis was analyzed by terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling staining and caspase-3 activity assays. The results indicate that increased expression of AT2R alone induced apoptosis in the prostate cancer lines, an effect that did not require Ang II. AT2R overexpression in DU145 cells induced inhibition of proliferation, a significant reduction of S-phase cells, and an enrichment of G₁-phase cells. The data also indicate that overexpression of AT2R led to apoptosis via an extrinsic cell death signaling pathway that is dependent on activation of p38 mitogen-activated protein kinase, caspase-8, and caspase-3. Finally, the apoptosis induced by AT2R overexpression is partially dependent on the activation of p53, but not on p21. The observations presented here suggest that the ability of increased AT2R expression to induce apoptosis in prostate cancer cells may have potential therapeutic implications for this disease, and suggest that AT2R is a promising novel target gene for prostate cancer gene therapy. [Mol Cancer Ther 2009;8(12):3255–65]

Cdc6 contributes to cisplatin-resistance by activation of ATR-Chk1 pathway in bladder cancer cells