The Epstein-Barr virus (EBV), a member of the human gamma-herpesviruses, is intricately linked to various human malignancies. Current treatment options for EBV infection involve the use of acyclovir and its derivatives, which exhibit limited efficacy and are associated with drug resistance issues. Therefore, there is a critical need for new medications with more effective therapeutic actions and less susceptibility to resistance. This review explores the therapeutic promise of flavones and flavonols, naturally occurring molecules, against EBV and its correlated cancers. It thoroughly delves into the molecular mechanisms underlying the therapeutic efficacy of these compounds and scrutinizes their complex interplay in EBV-linked processes and cancer transformation by targeting key genes and proteins pivotal to both the viral life cycle and tumor development. Additionally, the review covers current research, highlights key findings, and discusses promising avenues for future investigations in the pursuit of targeted therapies against EBV and its related tumors.

• Keywords
• EBV life cycle, EBV-associated cancers, Epstein–Barr virus, anticancer effects, antiviral properties, flavones, flavonoids, flavonols, host–EBV interaction, viral and cellular genes, viral and cellular proteins,
• MeSH
• Antiviral Agents * pharmacology   therapeutic use   chemistry   MeSH
• Flavonols * pharmacology   therapeutic use   chemistry   MeSH
• Flavones * pharmacology   therapeutic use   chemistry   MeSH
• Epstein-Barr Virus Infections * drug therapy   complications   virology   MeSH
• Humans MeSH
• Neoplasms * drug therapy   virology   MeSH
• Antineoplastic Agents pharmacology   therapeutic use   MeSH
• Herpesvirus 4, Human * drug effects   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Antiviral Agents * MeSH
• Flavonols * MeSH
• Flavones * MeSH
• Antineoplastic Agents MeSH

This current study seeks to examine the pre-protective function of Quercetin in Cadmium (Cd)-induced liver damage, along with its modulation of the PI3K/Akt/NF-kappaB signaling pathway. A total of 60 male C57BL/6J mice were randomly assigned to four groups: control (C), quercetin (Q, 100 mg/kg/day), Cd (Cd, 2.5 mg/kg/day), and quercetin and Cd (Q+Cd). Before receiving Cd treatment, quercetin was administered intragastrically for 4 weeks. In the present study, liver markers, oxidative stress parameters, pro-inflammatory cytokines, liver histopathology, apoptotic markers and PI3K/Akt/NF-kappaB signaling molecules were examined. We observed that the body weight of the Cd-treated mice dramatically rise after 4 weeks of quercetin pre-administration, and the Cd concentration was significantly decreased. Liver function markers like alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were significantly reduced in quercetin treatment in Cd-induced mice. Additionally, we observed that quercetin reduced Cd-mediated liver injury in mice by assessing the level of malondialdehyde (MDA), and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione (GSH) concentrations and the histological alterations. By monitoring tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1beta (IL-1beta), quercetin successfully reduced the inflammatory cytokines that the Cd metal caused in the liver. Additionally, in the liver tissues of Cd-mediated, quercetin could enhance the expression of Bcl-2 and decrease the expression of p-Akt, p-PI3K, Bax, Caspase-9, Caspase-3, NF-kappaB. In conclusion, quercetin protects against Cd induced liver injury via several pathways, including oxidative stress, inflammation and apoptosis, and its protective effect correlates with antioxidant activity.

• MeSH
• Antioxidants * pharmacology   MeSH
• Phosphatidylinositol 3-Kinases * metabolism   MeSH
• Liver drug effects   pathology   metabolism   MeSH
• Cadmium * toxicity   MeSH
• Chemical and Drug Induced Liver Injury * prevention & control   metabolism   pathology   MeSH
• Mice, Inbred C57BL * MeSH
• Mice MeSH
• NF-kappa B * metabolism   MeSH
• Oxidative Stress drug effects   MeSH
• Proto-Oncogene Proteins c-akt * metabolism   MeSH
• Quercetin * pharmacology   therapeutic use   MeSH
• Signal Transduction * drug effects   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Antioxidants * MeSH
• Phosphatidylinositol 3-Kinases * MeSH
• Cadmium * MeSH
• NF-kappa B * MeSH
• Proto-Oncogene Proteins c-akt * MeSH
• Quercetin * MeSH

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

• Keywords
• Autophagosome, LC3, cancer, flux, lysosome, macroautophagy, neurodegeneration, phagophore, stress, vacuole,
• MeSH
• Autophagy * physiology   MeSH
• Autophagosomes MeSH
• Biomarkers MeSH
• Biological Assay standards   MeSH
• Humans MeSH
• Lysosomes MeSH
• Autophagy-Related Proteins metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Guideline MeSH
• Names of Substances
• Biomarkers MeSH
• Autophagy-Related Proteins MeSH

Quercetin is a flavonoid largely employed as a phytochemical remedy and a food or dietary supplement. We present here a novel biocatalytic methodology for the preparation of quercetin from plant-derived rutin, with both substrate and product being in mostly an undissolved state during biotransformation. This "solid-state" enzymatic conversion uses a crude enzyme preparation of recombinant rutinosidase from Aspergillus niger yielding quercetin, which precipitates from virtually insoluble rutin. The process is easily scalable and exhibits an extremely high space-time yield. The procedure has been shown to be robust and was successfully tested with rutin concentrations of up to 300 g/L (ca 0.5 M) at various scales. Using this procedure, pure quercetin is easily obtained by mere filtration of the reaction mixture, followed by washing and drying of the filter cake. Neither co-solvents nor toxic chemicals are used, thus the process can be considered environmentally friendly and the product of "bio-quality." Moreover, rare disaccharide rutinose is obtained from the filtrate at a preparatory scale as a valuable side product. These results demonstrate for the first time the efficiency of the "Solid-State-Catalysis" concept, which is applicable virtually for any biotransformation involving substrates and products of low water solubility.

• Keywords
• Aspergillus niger, quercetin, rutin, rutinose, rutinosidase, “solid-state biocatalysis”,
• MeSH
• Aspergillus niger enzymology   genetics   MeSH
• Biocatalysis * MeSH
• Disaccharides chemistry   metabolism   MeSH
• Fungal Proteins genetics   metabolism   MeSH
• Glycoside Hydrolases genetics   metabolism   MeSH
• Pichia genetics   metabolism   MeSH
• Industrial Microbiology methods   MeSH
• Quercetin chemistry   metabolism   MeSH
• Rutin chemistry   metabolism   MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• beta-rutinosidase MeSH Browser
• Disaccharides MeSH
• Fungal Proteins MeSH
• Glycoside Hydrolases MeSH
• Quercetin MeSH
• Rutin MeSH
• rutinose MeSH Browser