Mycobacterium tuberculosis PE/PPE family proteins, named after the presence of conserved PE (Pro-Glu) and PPE (Pro-Pro-Glu) domains at N-terminal, are prevalent in M. tuberculosis genome. The function of most PE/PPE family proteins remains elusive. To characterize the function of PE_PGRS18, the encoding gene was heterologously expressed in M. smegmatis, a nonpathogenic mycobacterium. The recombinant PE_PGRS18 is cell wall associated. M. smegmatis PE_PGRS18 recombinant showed differential response to stresses and altered the production of host cytokines IL-6, IL-1β, IL-12p40 and IL-10, as well as enhanced survival within macrophages largely via attenuating the apoptosis of macrophages. In summary, the study firstly unveiled the role of PE_PGRS18 in physiology and pathogenesis of mycobacterium.

The cell membrane or biofilm serve as permeable barrier for xenobiotics to maintain the homeostasis of cells or bacterial community. Transport systems are essential for the uptake of nutrients and substances necessary for biofilm formation, efflux of deleterious compounds, as well as communication between cells and environment. Major facilitator superfamily (MFS) represents the largest secondary transporter family and is responsible for the transport of a broad spectrum of substrates with diverse physiochemical properties by utilizing the energy stored in electrochemical gradient across the membrane. Importantly, multidrug efflux pumps belonging to the major facilitator superfamily are important contributing factors to drug resistance and biofilm formation in many clinical strains like Mycobacterium tuberculosis. This review summarized the structural properties and functions of M. tuberculosis MFS transporters, molecular mechanisms of substrates transfer, and efflux pump inhibitors for better control of biofilm-associated infections.

Adrenocortical carcinoma (ACC), a rare malignant neoplasm originating from adrenal cortical cells, has high malignancy and few treatments. Therefore, it is necessary to explore the molecular mechanism of tumorigenesis, screen and verify potential biomarkers, which will provide new clues for the treatment and diagnosis of ACC. In this paper, three gene expression profiles (GSE10927, GSE12368 and GSE90713) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were obtained using the Limma package. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were enriched by DAVID. Protein-protein interaction (PPI) network was evaluated by STRING database, and PPI network was constructed by Cytoscape. Finally, GEPIA was used to validate hub genes' expression. Compared with normal adrenal tissues, 74 up-regulated DEGs and 126 down-regulated DEGs were found in ACC samples; GO analysis showed that up-regulated DEGs were enriched in organelle fission, nuclear division, spindle, et al, while down-regulated DEGs were enriched in angiogenesis, proteinaceous extracellular matrix and growth factor activity; KEGG pathway analysis showed that up-regulated DEGs were significantly enriched in cell cycle, cellular senescence and progesterone-mediated oocyte maturation; Nine hub genes (CCNB1, CDK1, TOP2A, CCNA2, CDKN3, MAD2L1, RACGAP1, BUB1 and CCNB2) were identified by PPI network; ACC patients with high expression of 9 hub genes were all associated with worse overall survival (OS). These hub genes and pathways might be involved in the tumorigenesis, which will offer the opportunities to develop the new therapeutic targets of ACC. | 4429GUO et al.

The eight subunits containing COP9 signalosome (CSN) complex, is highly conserved among eukaryotes. CSN, identified as a negative regulator of photomorphogenesis, has also been demonstrated to be important in proteolysis, cellular signal transduction and cell cycle regulation in various eukaryotic organisms. This review mainly summarizes the roles of CSN in cell cycle regulation, signal transduction and apoptosis, and its potential as diagnostic biomarkers, drug targets for cancer and infectious diseases. J. Cell. Physiol. 232: 1246-1253, 2017. © 2016 Wiley Periodicals, Inc.

Tuberculosis (TB) remains a highly contagious public health threat. Precise and prompt diagnosis and monitoring of treatment responses are urgently needed for clinics. To pursue novel and satisfied host blood-derived biomarkers, we streamlined a bioinformatic pipeline by integrating differentially expressed genes, a gene co-expression network, and short time-series analysis to mine the published transcriptomes derived from whole blood of TB patients in the GEO database, followed by validating the diagnostic performance of biomarkers in both independent datasets and blood samples of Chinese patients using quantitative real-time PCR (qRT-PCR). We found that four genes, namely UBE2L6 (Ubiquitin/ISG15-conjugating enzyme E2 L6), BATF2 (Basic leucine zipper transcriptional factor ATF-like), SERPING1 (Plasma protease C1 inhibitor), and VAMP5 (Vesicle-associated membrane protein 5), had high diagnostic value for active TB. The transcription levels of these four gene combinations can reach up to 88% sensitivity and 78% specificity (average) for the diagnosis of active TB; the highest sensitivity can achieve 100% by parallel of BATF2 and VAMP5, and the highest specificity can reach 89.5% through a combination of SERPIG1, UBE2L6, and VAMP5, which were significantly higher than 75.3% sensitivity and 69.1% specificity by T-SPOT.TB in the same patients. Quite unexpectedly, the gene set can assess the efficacy of anti-TB response and differentiate active TB from Latent TB infection. The data demonstrated these four biomarkers might have great potency and advantage over IGRAs in the diagnosis of TB.