Nuclear factor jB (NF-jB) is associated with the transcriptional activation of genes encoding chemokines, adhesion molecules, cytokines, and anti-apoptotic proteins, which are key components in immune responses and viral infection. Many viruses modulate NF-jB through numerous viral gene products to allow productive infections and immune escape. Here we report that herpes simplex virus-1 infected cell protein 27 (HSV-1 ICP27), an immediate early protein of HSV-1, represses NF-jB activity through binding to inhibitor of jB (IjBa), blocking phosphorylation and ubiquitination of IjBa, and stabilizing IjBa. These data may explain how NF-jB activity is regulated by ICP27 to escape immune responses during the very early period of HSV-1 infection.

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The curative effects of nanoparticle albumin-bound (nab)-paclitaxel in the first-line treatment of metastatic breast cancer (MBC) are still controversial, with even more after the removal of marketing approval of indication of bevacizumab. Five electronic databases and the related resources were searched for eligible randomized clinical trials (RCTs) without year and language restrictions to perform a meta-analysis. The studies were comparing the efficacy and safety between nab-paclitaxel chemotherapy versus solvent-based (sb)-taxanes chemotherapy such as sb-paclitaxel and docetaxel. The primary end points were overall response rate (ORR) and disease control rate (DCR). Secondary end points were progression-free survival (PFS), overall survival (OS), adverse events (AEs), and dose discontinuation rate (DDR). Five RCTs (1,554 patients) were finally identified from 1,902 studies. When compared to sb-paclitaxel, nab-paclitaxel showed significant beneficial effects in terms of ORR (OR 2.39, 95% CI 1.69-3.37, p < 0.001), DCR (OR 1.89, 95% CI 1.07-3.35, p = 0.03), and PFS (HR 0.75, 95% CI 0.62-0.90, p = 0.002). Nab-paclitaxel also showed significantly longer OS (HR 0.73, 95% CI 0.54-0.99, p = 0.04) than docetaxel. AEs and DDR were comparable between the two arms. Using nab-paclitaxel could significantly improve efficacy with comparable toxicities in the treatment of MBC. Nanoparticle albumin-bound (nab) paclitaxel is solvent free and employs a novel delivery mechanism for paclitaxel to tumors 1. Although nab-paclitaxel was initially developed to minimize the toxic effects of taxane treatment, several early clinical trials demonstrated that nab-paclitaxel was also more effective than the conventional solvent-based (sb) paclitaxel in the treatment of metastatic breast cancer 2-5. However, recent randomized controlled trials (RCTs) have suggested that nab-paclitaxel chemotherapy is not as efficacious as sb-taxanes, such as sb-paclitaxel and docetaxel, and that nab-paclitaxel is often associated with more frequent adverse events 6. For example, Rugo et al. showed that nab-paclitaxel was not superior to sb-paclitaxel (progression-free survival [PFS] 9.3 months vs 11 months, hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.00-1.45, p = 0.054). Results were concordant with overall survival (OS), and time to treatment failure was significantly shorter in the nab-paclitaxel arm vs the sb-paclitaxel arm 6. Hematologic and non-hematologic toxicity, including peripheral neuropathy, was more prevalent in the nab-paclitaxel arm, which also had more frequent and earlier dose reductions 6. After these conflicting results were generated, Liu et al. conducted a first meta-analysis of randomized clinical trials to evaluate the efficacy and toxicity of nab-paclitaxel compared with sb-paclitaxel and docetaxel in the

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