The Tat protein of human immunodeficiency virus-1 enhances hepatitis C virus replication through interferon gamma-inducible protein-10

<p>Abstract</p> <p>Background</p> <p>Co-infection with human immunodeficiency virus-1 (HIV-1) and hepatitis C virus (HCV) is associated with faster progression of liver disease and an increase in HCV persistence. However, the mechanism by which HIV-1 accelerates the progression of HCV liver disease remains unknown.</p> <p>Results</p> <p>HIV-1/HCV co-infection is associated with increased expression of interferon gamma-induced protein-10 (IP-10) mRNA in peripheral blood mononuclear cells (PBMCs). HCV RNA levels were higher in PBMCs of patients with HIV-1/HCV co-infection than in patients with HCV mono-infection. HIV-1 Tat and IP-10 activated HCV replication in a time-dependent manner, and HIV-1 Tat induced IP-10 production. In addition, the effect of HIV-1 Tat on HCV replication was blocked by anti-IP-10 monoclonal antibody, demonstrating that the effect of HIV-1 Tat on HCV replication depends on IP-10. Taken together, these results suggest that HIV-1 Tat protein activates HCV replication by upregulating IP-10 production.</p> <p>Conclusions</p> <p>HIV-1/HCV co-infection is associated with increased expression of IP-10 mRNA and replication of HCV RNA. Furthermore, both HIV-1 Tat and IP-10 activate HCV replication. HIV-1 Tat activates HCV replication by upregulating IP-10 production. These results expand our understanding of HIV-1 in HCV replication and the mechanism involved in the regulation of HCV replication mediated by HIV-1 during co-infection.</p

Molecular Characterization of Cultivated Bromeliad Accessions with Inter-Simple Sequence Repeat (ISSR) Markers

Bromeliads are of great economic importance in flower production; however little information is available with respect to genetic characterization of cultivated bromeliads thus far. In the present study, a selection of cultivated bromeliads was characterized via inter-simple sequence repeat (ISSR) markers with an emphasis on genetic diversity and population structure. Twelve ISSR primers produced 342 bands, of which 287 (~84%) were polymorphic, with polymorphic bands per primer ranging from 17 to 34. The Jaccard’s similarity ranged from 0.08 to 0.89 and averaged ~0.30 for the investigated bromeliads. The Bayesian-based approach, together with the un-weighted paired group method with arithmetic average (UPGMA)-based clustering and the principal coordinate analysis (PCoA), distinctly grouped the bromeliads from Neoregelia, Guzmania, and Vriesea into three separately clusters, well corresponding with their botanical classifications; whereas the bromeliads of Aechmea other than the recently selected hybrids were not well assigned to a cluster. Additionally, ISSR marker was proven efficient for the identification of hybrids and bud sports of cultivated bromeliads. The findings achieved herein will further our knowledge about the genetic variability within cultivated bromeliads and therefore facilitate breeding for new varieties of cultivated bromeliads in future as well

CAMK2N1 inhibits prostate cancer progression through androgen receptor-dependent signaling.

Castration resistance is a major obstacle to hormonal therapy for prostate cancer patients. Although androgen independence of prostate cancer growth is a known contributing factor to endocrine resistance, the mechanism of androgen receptor deregulation in endocrine resistance is still poorly understood. Herein, the CAMK2N1 was shown to contribute to the human prostate cancer cell growth and survival through AR-dependent signaling. Reduced expression of CAMK2N1 was correlated to recurrence-free survival of prostate cancer patients with high levels of AR expression in their tumor. CAMK2N1 and AR signaling form an auto-regulatory negative feedback loop: CAMK2N1 expression was down-regulated by AR activation; while CAMK2N1 inhibited AR expression and transactivation through CAMKII and AKT pathways. Knockdown of CAMK2N1 in prostate cancer cells alleviated Casodex inhibition of cell growth, while re-expression of CAMK2N1 in castration-resistant cells sensitized the cells to Casodex treatment. Taken together, our findings suggest that CAMK2N1 plays a tumor suppressive role and serves as a crucial determinant of the resistance of prostate cancer to endocrine therapies

The tumor suppressive role of CAMK2N1 in castration-resistant prostate cancer.

Prostate cancer at advanced stages including metastatic and castration-resistant cancer remains incurable due to the lack of effective therapies. The CAMK2N1 gene, cloned and characterized as an inhibitor of CaMKII (calcium/calmodulin-dependent protein kinase II), has been shown to affect tumorigenesis and tumor growth. However, it is still unknown whether CAMK2N1 plays a role in prostate cancer development. We first examined the protein and mRNA levels of CAMK2N1 and observed a significant decrease in human prostate cancers comparing to normal prostate tissues. Re-expression of CAMK2N1 in prostate cancer cells reduced cellular proliferation, arrested cells in G0/G1 phases, and induced apoptotic cell death accompanied by down-regulation of IGF-1, ErbB2, and VEGF downstream kinases PI3K/AKT, as well as the MEK/ERK-mediated signaling pathways. Conversely, knockdown of CAMK2N1 had a significant opposite effects on these phenotypes. Our analyses suggest that CAMK2N1 plays a tumor suppressive role in prostate cancer cells. Reduced CAMK2N1 expression correlates to human prostate cancer progression and predicts poor clinical outcome, indicating that CAMK2N1 may serve as a biomarker. The inhibition of tumor growth by expressing CAMK2N1 established a role of CAMK2N1 as a therapeutic target

The Performance of Pleural Fluid T-SPOT.TB Assay for Diagnosing Tuberculous Pleurisy in China: A Two-Center Prospective Cohort Study

The performance of T-SPOT.TB (T-SPOT) assay in diagnosing pleural tuberculosis (plTB) is inconsistent. In this study, we compared the performance of peripheral blood (PB) and pleural fluid (PF) T-SPOT assay in diagnosing plTB. Between July 2017 and March 2018, 218 and 210 suspected plTB patients were prospectively enrolled from Wuhan (training) and Guangzhou (validation) cohort, respectively. PB T-SPOT, PF T-SPOT, and other conventional tests were simultaneously performed. Our data showed the performance of PB T-SPOT in diagnosing plTB was limited, especially with low sensitivity. However, the results of early secreted antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) in PF T-SPOT were significantly increased compared with those in PB T-SPOT in plTB patients. If using 76 as the cutoff value of MAX (the larger of ESAT-6 and CFP-10) in Wuhan cohort, the sensitivity and specificity of PF T-SPOT to diagnose plTB were 89.76 and 96.70%, respectively. The diagnostic accuracy of PF T-SPOT was better than other routine tests such as pathogen detection methods and biochemical markers. The diagnostic accuracy of PF T-SPOT in Guangzhou cohort was similar to that in Wuhan cohort, with a sensitivity and specificity of 91.07 and 94.90%, respectively. Furthermore, CD4+ T cells were more activated in PF compared with PB, and the frequency of mycobacterium tuberculosis-specific CD4+ T cells in PF was significantly higher than that in PB in plTB patients. In conclusion, the performance of PF T-SPOT is obviously better than PB T-SPOT or other laboratory tests, which suggests that PF T-SPOT assay has been of great value in the diagnosis of pleural tuberculosis

Characterization of an Outbreak of Hand, Foot, and Mouth Disease in Nanchang, China in 2010

Recent outbreaks of human enterovirus 71 (EV71) infection and EV71-associated hand, foot, and mouth disease (HFMD) in China have affected millions and potentially lead to life-threatening complications in newborns. Furthermore, these outbreaks represent a significant global public health issue in the world. Understanding the epidemiology of HFMD and EV71 infection and their transmission patterns in China is essential for controlling outbreaks. However, no studies on the outbreaks of HFMD and EV71 infection in China during 2010 have been reported. In this report, we carried out an epidemiological analysis to study an outbreak of HFMD and EV71 infection in 2010 in the city of Nanchang in the Jiangxi province of People's Republic of China. From April 7 to May 11, 2010, a total of 109 HFMD cases were reported, and in this report the HFMD cases were studied by both epidemiological and laboratory analyses. The epidemiological study indicates that children aged younger than 8 years old represented more than 90% of the reported cases, with the age group of 1–3 years containing the highest number of cases. Laboratory studies detected a high prevalence of EV71 amongst the cases in our study, suggesting EV71 as a common enterovirus found in HFMD cases in Nanchang. Phylogenetic analysis of the sequence of the VP1 region of four EV71 isolates indicated that the Nanchang strains belong to the C4 subgenotype commonly found in China during outbreaks in 2008 but contain distinct variations from these strains. Our study for the first time characterizes the epidemiology of HFMD and EV71 infection in China in 2010 and furthermore, provides the first direct evidence of the genotype of EV71 circulating in Nanchang, China. Our study should facilitate the development of public health measures for the control and prevention of HFMD and EV71 infection in at-risk individuals in China

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