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Hepatitis C virus (HCV) infection causes high level of oxidative stress and hepatic inflammation primarily, and derives in different pathologies as liver cirrhosis, hepatic failure, and hepatocellular carcinoma (HCC). Currently available treatment is a combination of pegylated interferon-α and ribavirin, surgical resection, and liver transplantation. However, more than 50% of patients remain diseased and the treatment prior mentioned causes serious adverse effects and there is still no preventive vaccine available. Considering the limited treatment options, it remains the urgent need to find additional therapeutic agents. Chemoprevention is defined as the use of nontoxic substances and it has been considered as the alternative strategy to reduce the cancer development and carcinogenesis before invasion and metastasis occur. Polyphenols, such as ellagic acid, ellagitannins, and punicalagin and phenolic acids, such as gallic acid are abundant plant phenolic compounds and they are extracted from different fruit peels and seed. Those kinds of compounds are known to reduce the risk of disease and have shown to induce cytotoxicity in several cancer cell lines, including liver cell lines. In vitro and in vivo studies have shown that the GA has a positive effect on various liver diseases, such as hepatitis by HCV infection, hepatocellular carcinoma, steatosis, and fatty liver. Histopathology and serum biochemical studies in mice fed with a diet supplemented with GA, observed that GA protects against hepatic steatosis, obesity, hypercholesterolemia, and insulin resistance. This effect occurs in part through a reversing of the common high fat diet that caused disturbances to a range of metabolic pathways, including lipid metabolism, glucose metabolism (glycolysis and gluconeogenesis), and amino acids metabolism. On the other hand, GA also has in vitro effect in hepatocarcinoma cells that express nonstructural proteins of HCV reducing viral replication. Viral proteins expression and the levels of oxidative stress decreases the viability of liver cancer cells in cell culture. Some of the main action mechanisms are the activation of protein kinase ATM, dehydrogenase UDP-glucose, and NFκB pathway. In addition, when glutathione is depleted, induction of apoptotic, antiangiogenic effect, and inhibition of tumor cell proliferation is activated. For these reasons, the use of antioxidant compounds, particularly gallic acid, has been studied recently because it is a naturally abundant plant phenolic compound, it may be considered a tool as a biomarker, or alternative therapy in the prevention and treatment of liver diseases.

Background and aim. Acetylsalicylic acid (ASA) has been shown to downregulate HCV expression; however, the involved mechanisms are unknown. We used proteomic analysis to compare protein expression profiles between human hepatocarcinoma cells (Huh7) and Huh7-HCV cells harboring expression of non-structural HCV proteins, to elucidate the mechanism(s) involved in ASA-mediated downregulation of HCV replication. Material and methods. Both cell lines were treated or untreated with 4 mM ASA and harvested at 0, 24, 48 and 72 h to isolate total proteins, which were resolved by two-dimensional gel electrophoresis (2DE) to separate them by isoelectric point (pI), followed by fractionation by molecular weight (MW). Gels were scanned and analyzed with PD-Quest software V8.0.1, and proteins were elucidated by the specific pI and MW using TAGIDENT software. Statistics analysis included the t-test. Results and Discussion. Different protein patterns among hepatocytes expressing HCV-proteins in ASA treated and untreated cells were found. Among proteins differentially expressed in Huh7-HCV cells, we found proteins related to cell proliferation (MTMR6, FAM22, HDGF and HCF-1) after 24 h of ASA treatment; and upregulation of angiostatin, PI4KA and STAT-1 after 48 h of treatment. Finally, at 72 h of ASA exposure, we identified overexpression of adenylsuccinate synthase, 2’-3’-di-deoxyadenosine, ubiquitin-protein-ligase E6A, adenylosuccinate-lyase and nibrin (NBN). Conclusion. We found that ASA induces different protein patterns in Huh7-HCV cells promoting activation of proteins involved in cell progression, repair of double strand breaks, proliferation, inhibition of apoptosis and growth stimulation at the same time that it decreased HCV expression.

Development of multidrug-resistant bacteria (MDRB) and demand by consumers of fresher foods with no chemical preservatives added, and minimally processed with long shelf life, have increased demand for new antibacterial compounds, which has stimulated the identification, development, and redesign of antibiotics. For this reason, different antibacterial agents, including antimicrobial peptides (AMPs) and bacteriocins are now being reevaluated. The latter compounds are peptides produced by different bacteria, which may act against a wide range of pathogens. Some of them are closely related to spoilage and disease-causing Gram-positive bacteria. In this chapter, we reviewed the use of bacteriocins for the control of MDRB. Bacteriocins have different applications in the food industry, especially for biopreservation and shelf-life extension, also as clinical antimicrobials and as microbial control during fermentation. There are different types of bacteriocins successfully applied in the food industry, such as nisin and pedicin PA-1/AcH, which have been authorized to be used as bio-preservatives. But they are only a small fraction of the diversity of these bacteriocins. Bacteriocins are a good option to use against multidrug-resistant (MDR) pathogens in clinical cases because these AMPs may act at picomolar and nanomolar concentrations and with high specificity. Continuous research will lead to obtaining more diverse and efficient antimicrobial bacteriocins; in this case, recent development of new techniques for identification, purification, and heterologous proteins will allow for new antibiotics that can control MDRB.