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Malignancy of the lung is a major source of morbidity and mortality in persons with human immunodeficiency virus infection; as the most prevalent non-acquired immunodeficiency syndrome-defining malignancy, it represents an important and growing problem confronting HIV-infected patients. To evaluate the molecular changes of lung malignancy in HIV infection, we analyzed differential gene expression profiles and screened for early detection biomarkers of HIV-associated lung cancer using Affymetrix arrays and IPA analysis. A total of 59 patients were diagnosed with HIV-associated lung cancer from Jan 2010 to May 2018. The primary outcome was a significant difference in survival outcome between stages III-IV (10.46 ± 1.87 months) and I-II (17.66 ± 2.88 months). We identified 758 differentially expressed genes in HIV-associated lung cancer. The expression levels of SIX1 and TFAP2A are specifically increased in HIV-associated lung cancer and are associated with poorly differentiated tumor tissue. We also found decreased ADH1B, INMT and SYNPO2 mRNA levels in HIV lung cancer. A comprehensive network and pathway analysis of the dysregulated genes revealed that these genes were associated with four network functions and six canonical pathways relevant to the development of HIV-associated lung cancer. The molecular changes in lung malignancy may help screen the growing population of HIV patients who have or will develop this malignancy.

// Zenglin Pei 1 , Song-Mei Liu 2 , Jing-Tao Huang 2 , Xuan Zhang 1 , Dong Yan 3 , Qianlin Xia 1 , Chunxia Ji 1 , Weiping Chen 4 , Xiaoyan Zhang 1 , Jianqing Xu 1 , Jin Wang 1 1 Scientific Research Center, Shanghai Public Health Clinical Center, Fudan University, Jinshan District, Shanghai 201508, P.R. China 2 Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China 3 Department of Medical Oncology, Beijing Chaoyang Hospital affiliated to Capital Medical University, Beijing, China 4 Genomics Core, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA Correspondence to: Jin Wang, email: wangjin@shaphc.org Keywords: pancreatic cancer, meta-analysis, diagnostics, multiple miRNA, SROC Received: October 24, 2016 Accepted: January 25, 2017 Published: February 07, 2017 ABSTRACT Background: Pancreatic cancer (PaCa) is the most lethal gastrointestinal (GI) tumor. Although many studies on differentially expressed miRNAs as candidate biomarkers of pancreatic cancer have been published, reliability of these findings generated from investigations performed in single laboratory settings remain unclear. Results: There were 29 articles with a total of 2,225 patients and 1,618 controls included in this meta-analysis. The pooled sensitivity was 82% (95% CI, 79–85%); the specificity was 85% (95% CI, 79–89%); and area under the curve (AUC) was 0.89 (95% CI, 0.86–0.92). Subgroup analyses indicated that there were significant divergences between Caucasian and Asian subgroups for circulating miRNA analysis. Materials And Methods: To comprehensively investigate the potential utility of miRNAs as biomarkers of the disease, we searched publications diagnosing PaCa using miRNAs from PubMed, Medline, Embase, Google Scholar and Chinese National Knowledge Infrastructure (CNKI) databases. The sensitivity (SEN), specificity (SPE), and summary receiver operating characteristic (SROC) curve were used to examine the overall test performance, and heterogeneity was analyzed with the I 2 test. Conclusions: Our analysis demonstrated that multiple miRNAs (SEN: 85%; SPE: 89%; AUC: 0.93) were more accurate for diagnosing PaCa than a single miRNA (SEN: 78%; SPE: 79%; AUC: 0.84), and future studies are still needed to confirm the diagnostic value of these pooled miRNAs for PaCa.

Background and purpose Tuberculosis is one of the most highly fatal diseases worldwide, and one-third of the world's population has been infected with Mycobacterium tuberculosis (M. tuberculosis). A previous study showed that M. tuberculosis was highly susceptible to being killed by ascorbate (i.e. vitamin C, VC), but the molecular mechanisms of the bactericidal activity of VC against M. tuberculosis are still not well understood. Experimental approach We assayed the effects of VC as an anti-tuberculosis drug against mycobacteria (i.e. M. bovis BCG or M. tuberculosis H37Rv) in macrophages (i.e. RAW 264.7 cells). Relative global protein expression changes in 5 mM VC-treated and control samples of H37Rv were investigated by Tandem mass tag (TMT)-based quantitative proteomic analysis. qRT-PCR was also used to measure the differential expression of six intracellular stress response mycobacteria genes. Key results Quantitative proteomic analysis showed that 11 peptide components including rip3, fdxA, Rv2028c, mtp, LH57_00670, hspX, pfkB, Rv1824, Rv1813c, LH57_08410 and Rv2030c were up-regulated and 17 peptide components were down-regulated in 5 mM VC-treated H37Rv compared with the control samples. qRT-PCR also verified that VC could induce the expression of six genes (hsp, fdxD, furA, devR, hspX, and dnaB) in BCG and H37Rv. We also found that exosomes from RAW 264.7 cells treated with pharmacologic VC could kill M. bovis BCG in vitro. Conclusion and implications Our results demonstrated that the bactericidal activity of VC against mycobacteria, as a pro-drug for hydrogen peroxide formation (H2O2), was dependent on reactive oxygen species production and the activated oxidative stress pathway, which suggested that pharmaceutical VC and exosomes from macrophages treated with VC could be used as potential anti-tuberculosis drugs.

// Zenglin Pei 1, * , Xuan Zhang 1, * , Chunxia Ji 1 , Song-Mei Liu 2 , Jin Wang 1 1 Scientific Research Center, Shanghai Public Health Clinical Center, Jinshan District, Shanghai 201508, China 2 Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China * These authors contributed equally to this work Correspondence to: Jin Wang, email: wangjin@shaphc.org Keywords: drug resistance, transcriptomic profiles, pathway analysis, ascorbate, Burkitt lymphoma cells Received: April 14, 2016 Accepted: August 24, 2016 Published: August 31, 2016 ABSTRACT Ascorbate is a pro-oxidant that generates hydrogen peroxide–dependent cytotoxity in cancer cells without adversely affecting normal cells. To determine the mechanistic basis for this phenotype, we selected Burkitt lymphoma cells resistant to ascorbate (JLPR cells) and their ascorbate-sensitive parental cells (JLPS cells). Compared with JLPS cells, the increased glucose uptake in JLPR cells (with upregulated glucose transporters, increased antioxidant enzyme activity, and altered cell cycling) conferred ascorbate–induced cytotoxicity and resistance. Transcriptomic profiles and function pathway analysis identified differentially expressed gene signatures for JLPR cells and JLPS cells, which differential expression levels of five genes ( ATF5, CD79B, MHC, Myosin , and SAP18 ) in ascorbate-resistant cells were related to phosphoinositide 3 kinase, cdc42 , DNA methylation and transcriptional repression, polyamine regulation, and integrin-linked kinase signaling pathways. These results suggested that coordinated changes occurred in JLPR cells to enable their survival when exposed to the cytotoxic pro-oxidant stress elicited by pharmacologic ascorbate treatment.

Exosomes, as a subset of extracellular vesicles, function as a mode of intercellular communication and molecular transfer, and facilitate the direct extracellular transfer of proteins, lipids, and miRNAs/mRNAs/DNAs between cells. Cancers have adapted exosomes and related microvesicles as a pathway that can suppress the immune system and establish a fertile local and distant environment to support neoplastic growth, invasion, and metastasis; these tumor-derived exosomes affect immunoregulation mechanisms, including immune activation and immune suppression. Immune cell-derived exosomes can modulate the immune response in cancer, which supports the belief that these membranous vesicles are immunotherapeutic reagents. In this review, we discuss the recent advances in the cancer immunotherapy, roles of exosomes in cancer, immunoregulation of tumor-derived exosomes, and immunomodulation by immune cell-derived exosomes. The topics covered here highlight novel insights into the development of efficient exosome-based cancer vaccines for cancer therapeutic intervention.

Additional file 2. Differentially expressed genes identified from the series GSE6740.

Background: On March 31, 2013, human infections with a novel avian influenza A (H7N9) virus were firstly reported in China. By February 7, 2015, a total of 562 laboratory-confirmed human cases of H7N9 infection were reported in mainland China. Objectives: This study aimed to determine whether there is a novel H7N9 virus infection in human and animals in Taizhou city, China, in 2013. Methods: In this study, we developed real-time reverse transcription-polymerase chain reaction (RT-PCR) assays to detect H7N9 virus infection in human and animals (chicken, pig, and pigeon) in Taizhou city in the beginning of H7N9 epidemics of 2013. Also, we studied the novel isolated H7N9 virus strain by using genome sequencing and phylogenetic analysis. Results: Of 150 samples tested, 7 were detected to be H7N9 positive which all were collected from chickens. Also, a novel H7N9 virus strain (A/chicken/jiangsu/1021/2013) was isolated and studied. Phylogenetic analysis showed the novel isolated H7N9 virus had high identity to the four novel human H7N9 viruses (A/Shanghai/1/2013, A/Shanghai/2/2013, A/Anhui/1/2013, and A/Hangzhou/1/2013). Conclusions: Our results demonstrated a novel H7N9 virus in chickens in Taizhou city in 2013 that may pose a potential risk to public health.

Attenuated strains of invasive enteric bacteria, such as Salmonella, represent promising gene delivery agents for nucleic acid-based vaccines as they can be administrated orally. In this study, we constructed a novel attenuated strain of Salmonella for the delivery and expression of the hemagglutinin (HA) and neuraminidase (NA) of a highly pathogenic H5N1 influenza virus. We showed that the constructed Salmonella strain exhibited efficient gene transfer activity for HA and NA expression and little cytotoxicity and pathogenicity in mice. Using BALB/c mice as the model, we evaluated the immune responses and protection induced by the constructed Salmonella-based vaccine. Our study showed that the Salmonella-based vaccine induced significant production of anti-HA serum IgG and mucosal IgA, and of anti-HA interferon-γ producing T cells in orally vaccinated mice. Furthermore, mice orally vaccinated with the Salmonella vaccine expressing viral HA and NA proteins were completely protected from lethal challenge of highly pathogenic H5N1 as well as H1N1 influenza viruses while none of the animals treated with the Salmonella vaccine carrying the empty expression vector with no viral antigen expression was protected. These results suggest that the Salmonella-based vaccine elicits strong antigen-specific humoral and cellular immune responses and provides effective immune protection against multiple strains of influenza viruses. Furthermore, our study demonstrates the feasibility of developing novel attenuated Salmonella strains as new oral vaccine vectors against influenza viruses.

Controlled regulation of genomic DNA synthesis is a universally conserved process for all herpesviruses, including human cytomegalovirus (HCMV), and plays a key role in viral pathogenesis, such as persistent infections. HCMV UL105 is believed to encode the helicase of the DNA replication machinery that needs to localize in the nuclei, the site of viral DNA synthesis. No host factors that interact with UL105 have been identified. In this study, we show that UL105 specifically interacts with Snapin, a human protein that is predominantly localized in the cytoplasm and associated with cellular vesicles. UL105 was found to interact with Snapin in both the yeast two-hybrid screen and coimmunoprecipitation experiments in HCMV-infected cells. The nuclear and cytoplasmic levels of UL105 were decreased and increased in cells overexpressing Snapin, respectively, while the levels of UL105 in the nuclei and cytoplasm were increased and decreased in cells in which the expression of Snapin was downregulated with anti-Snapin small interfering RNA (siRNA) molecules, respectively. Furthermore, viral DNA synthesis and progeny production were decreased in cells overexpressing Snapin and increased in the anti-Snapin siRNA-treated cells, respectively. Our results provide the first direct evidence to suggest that Snapin interacts with UL105 and alters its cellular distribution, leading to modulation of viral DNA synthesis and progeny production. Our study further suggests that modulation of the cellular distribution of viral helicase by Snapin may represent a possible mechanism for regulating HCMV genomic DNA synthesis, a key step during herpesvirus lytic and persistent infections.

The above article from the Journal of Cellular Physiology, published online on 10 March 2016 in Wiley Online Library as Early View (http://onlinelibrary.wiley.com/enhanced/doi/10.1002/jcp.25353/), has been retracted by agreement between Gary Stein, the journal's Editor-in-Chief, and Wiley Periodicals, Inc. The retraction has been agreed following an investigation at the University of Texas, MD Anderson Cancer Center, which confirmed that the article was submitted and approved for publication by Dr. Jin Wang without acknowledgement of NIH funding received or the consent and authorship of Dr. Ann Killary and Dr. Subrata Sen, with whom the manuscript was originally drafted.