Human Viral Oncoproteins and Ubiquitin-Proteasome System.

Some human cancers worldwide may be related to human tumor viruses. Knowing, controlling, and managing the viruses that cause cancers remain a problem. Also, tumor viruses use ubiquitin-proteasome system (UPS) that can alter host cellular processes through UPS. Human tumor viruses cause persistent infections, due to their ability to infect their host cells without killing them. Tumor viruses such as Epstein-Barr virus, hepatitis C virus, hepatitis B virus, human papillomaviruses, human T cell leukemia virus, Kaposi's sarcoma-associated herpesvirus, and Merkel cell polyomavirus are associated with human malignancies. They interfere with the regulation of cell cycle and control of apoptosis, which are important for cellular functions. These viral oncoproteins bind directly or indirectly to the components of UPS, modifying cellular pathways and suppressor proteins like p53 and pRb. They can also cause progression of malignancy. In this review, we focused on how viral oncoproteins bind to the components of the UPS and how these interactions induce the degradation of cellular proteins for their survival.

Accuracy of diagnostic assays for the detection of Clostridioides difficile: A systematic review and meta-analysis.

INTRODUCTION: Clostridioides difficile Infection (CDI) has been identified as one of the main causes of nosocomial infection all across the world. Rapid diagnosis of CDI is difficult and poses a significant challenge to physicians worldwide. We undertook a systematic review and meta-analysis to evaluate rapid tests' diagnostic accuracy against toxigenic culture as the reference standard for CDI. METHOD: We searched the PubMed/MEDLINE and EMBASE databases for the relevant records. The QUADAS-2 tool was used to assess the quality of the studies. Diagnostic accuracy measures [i.e., sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratios (PLR), negative likelihood ratios (NLR), and the area under the curve (AUC)] were pooled with a random-effects model. All statistical analyses were performed with Meta-DiSc (Version 1.4, Cochrane Colloquium, Barcelona, Spain) and RevMan (version 5.3; The Nordic Cochrane Centre, the Cochrane Collaboration, Copenhagen, Denmark). RESULTS: We reviewed retrieved records and identified 63 studies that met the inclusion criteria. 26 were about enzyme immunoassay (EIA) (our main index test). The sensitivity of GDH and Tox A/B EIAs were 82% (95% CI: 79-84) and 75% (95% CI: 70-79), respectively. On the other hand, the specificity of GDH EIA was 91% (95% CI: 90-92) and the specificity of Tox A/B EIA was 95% (95% CI: 94-96). Among other index tests, BD Max with 92% has the most sensitivity and cell cytotoxicity neutralization assay (CCNA) has the most specificity (100%). CONCLUSION: This meta-analysis demonstrated that EIAs could be reliable methods for detecting CDI based on their sensitivity, specificity, time and cost-effectiveness, and simplicity in the procedure. Further work to improve rapid tests would benefit from improvements to the methodology.

Anti-proliferative effects of cell wall, cytoplasmic extract of Lactococcus lactis and nisin through down-regulation of cyclin D1 on SW480 colorectal cancer cell line.

BACKGROUND AND OBJECTIVES: Colorectal cancer is one of the most types of cancer. Researchers have shown that lactic acid bacteria have antitumor activity. The cell wall of Lactococcus lactis, as the bacterial cytoplasmic extract and nisin can affect the proliferation of cancer cells. Since cyclin D1 plays an important role in the progression of the cell cycle, its regulation can also be a therapeutic approach. We investigated the antiproliferative effect of cell wall, cytoplasmic extract and nisin on SW480 cancer cell line and the expression level of cyclin D1 gene in treated cancer cells. MATERIALS AND METHODS: SW480 cell lines were treated with different concentrations of bacterial cell wall, cytoplasmic extract and nisin. MTT test was also performed. The expression level of cyclin D1 gene was determined using Real time PCR. Data were analyzed using Graph Pad Prism software. RESULTS: The growth rate of cancer cells treated with nisin has significantly decreased compared to the cancer cells treated by other two substances (p< 0.05). Survival rates of the cancer cells treated by nisin at a concentration of 2000 µg, cytoplasmic extract, and cell wall were 34%, 47% and 49%, respectively. Real-time PCR results showed that cyclin D1 mRNA expression has significantly decreased in nisin treated sw480 cells (P<0.05). CONCLUSION: The results of this study show that nisin, bacterial cytoplasmic extract, and bacterial cell wall have antiproliferative effects, which are associated with the decreased expression of cyclin D1 in SW480 cell line.