Long noncoding RNA LINC00662 functions as miRNA sponge to promote the prostate cancer tumorigenesis through targeting miR-34a.

OBJECTIVE: Mounting evidence indicates that long noncoding RNAs (lncRNAs) play a critical role in the tumorigenesis. Up-regulation of lncRNA LINC00662 (LINC00662) has previously confirmed in several tumors. However, the study of LINC00662 in prostate cancer (PCa) is limited. Hence, to determine the expression pattern and function of LINC00662 in PCa. PATIENTS AND METHODS: LINC00662 expression was first detected in PCa cell lines and tissue samples by qRT-PCR. Based on follow-up data, correlations of LINC00662 expression and clinicopathological features, including overall survival, in PCa patients were evaluated. Cell proliferation, migration, invasion, and apoptosis were detected by CCK-8 assay, colony-forming assay, Wound-healing assay, transwell assay, and flow cytometry, respectively. Additionally, LINC00662-specific miRNA was further confirmed using the dual-luciferase reporter assay and RT-PCR. RESULTS: LINC00662 was significantly upregulated in PCa tissues and cell lines compared with adjacent normal tissue and a normal prostate epithelial cell line. Higher expression of LINC00662 was positively associated with distant metastasis and shorter overall survival. In addition, multivariate analysis revealed that tissue LINC00662 expression was confirmed to be an independent prognostic factor for PCa. Furthermore, LINC00662 silencing inhibited the proliferation, migration, and invasion of PC-3 and LNCaP cells, and promoted apoptosis in vitro. Bioinformatics methods and luciferase reporter assay revealed the close link within miR-34a and 3'-untranslated region (UTR) of LINC00662 and further confirmed that LINC00662 could function as a sponge of miR-34a in PCa cells. Also, the results of RT-PCR showed that knockdown of LINC00662 suppressed the expression levels of miR-34a. CONCLUSIONS: The current results further enhanced our understanding of the effects of LINC00662 in PCa and may help to provide a new potential target for PCa treatment.

Antibodies: can they protect against HIV infection?

More than 20 million people have died since the discovery of human immunodeficiency virus (HIV), yet a broadly reactive AIDS vaccine remains elusive. Neutralizing antibody (nAb) response-based vaccine strategies were the first to be tested; however, when the difficulty in neutralizing primary HIV isolates was recognized, vaccine development focused instead on generating cytotoxic T-lymphocyte (CTL) responses. Recently, interest in anti-HIV nAbs has been revived by the impressive protection achieved in primates given passive immunization with neutralizing monoclonal antibodies (nmAbs) isolated from HIV clade B-infected individuals. The nmAbs used in these studies target conserved, functionally important epitopes in HIV gp120 and gp41. Regimens involving combinations of such human nmAbs or high-dose single-agent nmAb protected monkeys against intravenous (iv) and mucosal challenges with simian-human immunodeficiency virus (SHIV) strains encoding X4, X4R5 or R5 HIV env genes. In several such studies, sterilizing immunity was achieved, thus providing proof-of-concept that nAbs targeting conserved epitopes can be fully protective. The existence of these broadly reactive nmAbs suggests that it may be possible to design immunogens capable of inducing similar nAb responses by active vaccination. Unraveling the three-dimensional structures involved in the nmAb-HIV Env epitope interactions may facilitate the future development of a potent AIDS vaccine. This review is focused on the importance of nAbs in protecting against HIV infection or in containing viral spread, with particular emphasis on the successful use of nmAbs in passive immunization studies. The implications of the data from these studies on AIDS vaccine design in general are also discussed.

Nitrogen dioxide in indoor ice skating facilities: an international survey.

An international survey of nitrogen dioxide (NO2) levels inside indoor ice skating facilities was conducted. One-week average NO2 concentrations were measured inside and outside of 332 ice rinks located in nine countries. Each rink manager also completed a questionnaire describing the building, the resurfacing machines, and their use patterns. The (arithmetic) mean NO2 level for all rinks in the study was 228 ppb, with a range of 1-2,680 ppb, based on a sample collected at breathing height and adjacent to the ice surface. The mean of the second indoor sample (collected at a spectator's area) was 221 ppb, with a range of 1-3,175 ppb. The ratio of the indoor to outdoor NO2 concentrations was above 1 for 95% of the rinks sampled, indicating the presence of an indoor NO2 source (mean indoor:outdoor ratio = 20). Estimates of short-term NO2 concentrations indicated that as many as 40% of the sampled rinks would have exceeded the World Health Organization 1-hour guideline value of 213 ppb NO2 for indoor air. Statistically significant associations were observed between NO2 levels and the type of fuel used to power the resurfacer, the absence of a catalytic converter on a resurfacer, and the use of an ice edger. There were also indications that decreased use of mechanical ventilation, increased number of resurfacing operations per day, and smaller rink volumes were associated with increased NO2 levels. In rinks where the main resurfacer was powered by propane, the NO2 concentrations were higher than in those with gasoline-powered resurfacers, while the latter had NO2 concentrations higher than in those using diesel. Rinks where the main resurfacer was electric had the lowest indoor NO2 concentrations, similar to the levels measured outdoors.

Molecularly cloned SHIV-1157ipd3N4: a highly replication- competent, mucosally transmissible R5 simian-human immunodeficiency virus encoding HIV clade C Env.

Human immunodeficiency virus type 1 (HIV-1) clade C causes >50% of all HIV infections worldwide, and an estimated 90% of all transmissions occur mucosally with R5 strains. A pathogenic R5 simian-human immunodeficiency virus (SHIV) encoding HIV clade C env is highly desirable to evaluate candidate AIDS vaccines in nonhuman primates. To this end, we generated SHIV-1157i, a molecular clone from a Zambian infant isolate that carries HIV clade C env. SHIV-1157i was adapted by serial passage in five monkeys, three of which developed peripheral CD4(+) T-cell depletion. After the first inoculated monkey developed AIDS at week 137 postinoculation, transfer of its infected blood to a naïve animal induced memory T-cell depletion and thrombocytopenia within 3 months in the recipient. In parallel, genomic DNA from the blood donor was amplified to generate the late proviral clone SHIV-1157ipd3. To increase the replicative capacity of SHIV-1157ipd3, an extra NF-kappaB binding site was engineered into its 3' long terminal repeat, giving rise to SHIV-1157ipd3N4. This virus was exclusively R5 tropic and replicated more potently in rhesus peripheral blood mononuclear cells than SHIV-1157ipd3 in the presence of tumor necrosis factor alpha. Rhesus macaques of Indian and Chinese origin were next inoculated intrarectally with SHIV-1157ipd3N4; this virus replicated vigorously in both sets of monkeys. We conclude that SHIV-1157ipd3N4 is a highly replication-competent, mucosally transmissible R5 SHIV that represents a valuable tool to test candidate AIDS vaccines targeting HIV-1 clade C Env.

Remaining small bowel length: association with catheter sepsis in patients receiving home total parenteral nutrition: evidence of bacterial translocation.

Patients with short bowel syndrome (SBS) receiving total parenteral nutrition (TPN) have a high incidence of catheter-related sepsis, one of its major complications. The aim of this study was to correlate the length of remaining small bowel (RSB) with septic episodes related to the central venous catheter in a group of patients with severe SBS with home TPN. The length of the RSB (<50 cm or > or = 50 cm) was related to the frequency of catheter sepsis, time until the first episode, and the agents responsible in eight SBS patients receiving home TPN. There were 13 episodes of catheter infection (0.88 per patient-year). The group with a shorter RSB length (five patients) presented 1.3 to 2.76 infections/year and 2 to 9 months until the first episode, compared to 0 to 0.75 infections/ year (p = 0.0357) and 11 to 65 months until the first episode (p = 0.0332) in the group with the longer RSB. In the first group, the agents isolated were Enterobacteriae (Enterobacter sp., Klebsiella sp., Pseudomonas sp., and Proteus sp.) in eight episodes and Candida sp. in one. In the latter sepsis was caused by Staphylococcus sp. in three episodes and Pseudomonas sp. in one. Therefore patients with remaining small bowel shorter than 50 cm have a higher frequency of catheter-related sepsis, particularly by enteric microorganisms. This might be an evidence of the occurrence of bacterial translocation and its role in the pathogenesis of catheter-related sepsis in patients with an extremely short RSB receiving home TPN.