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BACKGROUND: Resistance to antibiotics and anticancer therapy is a serious global health threat particularly in immunosuppressed cancer patients. Current study aimed to estimate the antibacterial and anticancer potentials of short-term exposure to extremely low frequency electromagnetic field (ELF-EMF) and silver nanoparticles (AgNPs) either in sole or combined form. METHODS: Antibacterial activity was evaluated via determination of the bacterial viable count reduction percentage following exposure, whereas their ability to induce apoptosis in breast cancer (MCF-7) cell line was detected using annexin V-fluorescein isothiocyanate and cell cycle analysis. Also, oxidative stress potential and molecular profile were investigated. RESULTS: ELF-EMF and AgNPs significantly (p < 0.01) reduced K. pneumonia viable count of compared to that of S. aureus in a time dependent manner till reaching 100% inhibition when ELF-EMF was applied in combination to 10 µM/ml AgNPs for 2 h. Apoptosis induction was obvious following exposure to either ELF-EMF or AgNPs, however their apoptotic potential was intensified when applied in combination recording significantly (p < 0.001) induced apoptosis as indicated by elevated level of MCF-7 cells in the Pre G1 phase compared to control. S phase arrest and accumulation of cells in G2/M phase was observed following exposure to AgNPs and EMF, respectively. Up-regulation in the expression level of p53, iNOS and NF-kB genes as well as down-regulation of Bcl-2 and miRNA-125b genes were detected post treatment. CONCLUSIONS: The antibacterial and anticancer potentials of these agents might be related to their ability to induce oxidative stress, suggesting their potentials as novel candidates for controlling infections and triggering cancer cells towards self-destruction.
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The present work aimed to study the activity of naturally derived fungal secondary metabolites as anticancer agents concerning their cytotoxicity, apoptotic, genetic, and histopathological profile. It was noticed that Aspergillus terreus, Aspergillus flavus, and Aspergillus fumigatus induced variable toxic potential that was cell type, secondary metabolite type, and concentration dependent. Human colonic adenocarcinoma cells (Caco-2) showed less sensitivity than hepatocyte-derived cellular carcinoma cells (HuH-7), and in turn, the half-maximal inhibitory concentration (IC50) was variable. Also, the apoptotic potential of Aspergillus species-derived fungal secondary metabolites was proven via detection of up-regulated pro-apoptotic genes and down-regulation of anti-apoptotic genes. The expression level was cell type dependent. Concurrently, apoptotic profile was accompanied with cellular DNA accumulation at the G2/M phase, as well as an elevation in Pre-G1 phase but not during G0/G1 and S phases. Also, there were characteristic apoptotic features of treated cells presented as abnormal intra-nuclear eosinophilic structures, dead cells with mixed euchromatin and heterochromatin, ruptured cell membranes, apoptotic cells with irregular cellular and nuclear membranes, as well as peripheral chromatin condensation. It can be concluded that Aspergillus secondary metabolites are promising agents that can be used as supplementary agents to the currently applied anti-cancer drug regimen.
Asunto(s)
Antineoplásicos , Apoptosis , Antineoplásicos/farmacología , Células CACO-2 , HumanosRESUMEN
PURPOSE: One of the essential goals regarding the successful control of rabies infection is the development of a safe, effective, and inexpensive vaccine. the current study aimed to evaluate the inactivation potential of ß-propiolactone (ßPL), binary ethyleneimine (BEI), and hydrogen peroxide (H2O2). MATERIALS AND METHODS: Estimating the inactivation kinetics of ßPL, BEI, and H2O2 revealed that the tested inactivants could completely and irreversibly inactivate rabies virus within 2, 12, and 4 hours, respectively while maintaining its viral immunogenicity. The potency of ßPL, BEI, and H2O2 inactivated vaccines was higher than the World Health Organization acceptance limit and were in the order of 3.75, 4.21, and 3.64 IU/mL, respectively. Monitoring the humoral and cellular immunity elicited post-immunization using Staphylococcus aureus derived hyaluronic acid (HA) and bacillus Calmette-Guérin purified protein derivative (PPD) adjuvanted rabies vaccine candidates were carried out using enzyme-linked immunosorbent assay. RESULTS: Results demonstrated that both adjuvants could progressively enhance the release of anti-rabies total immunoglobulin G as well as the pro-inflammatory mediators (interferon-gamma and interleukin-5) relative to time. However, a higher immune response was developed in the case of HA adjuvanted rabies vaccine compared to PPD adjuvanted one. The harmful consequences of the tested adjuvants were considered via investigating the histopathological changes in the tissues of the immunized rats using hematoxylin and eosin stain. Lower adverse effects were observed post-vaccination with HA and PPD adjuvanted vaccines compared to that detected following administration of the currently used alum as standard adjuvant. CONCLUSION: Our findings suggested that HA and PPD could serve as a promising platform for the development of newly adjuvanted rabies vaccines with elevated immune enhancing potentials and lower risk of health hazards.