Abstract

The interaction between silver nanoparticles and herpesviruses is attracting great interest due to their antiviral activity and possibility to use as microbicides for oral and anogenital herpes. In this work, we demonstrate that tannic acid modified silver nanoparticles sized 13 nm, 33 nm and 46 nm are capable of reducing HSV-2 infectivity both in vitro and in vivo. The antiviral activity of tannic acid modified silver nanoparticles was size-related, required direct interaction and blocked virus attachment, penetration and further spread. All tested tannic acid modified silver nanoparticles reduced both infection and inflammatory reaction in the mouse model of HSV-2 infection when used at infection or for a post-infection treatment. Smaller-sized nanoparticles induced production of cytokines and chemokines important for anti-viral response. The corresponding control buffers with tannic acid showed inferior antiviral effects in vitro and were ineffective in blocking in vivo infection. Our results show that tannic acid modified silver nanoparticles are good candidates for microbicides used in treatment of herpesvirus infections.

Introduction: Silver nanoparticles (AgNPs) have been shown to promote wound healing and to exhibit antimicrobial properties against a broad range of bacteria. In our previous study, we prepared tannic acid (TA)-modified AgNPs showing a good toxicological profile and immunomodulatory properties useful for potential dermal applications. Methods: In this study, in vitro scratch assay, antimicrobial tests, modified lymph node assay as well as a mouse splint wound model were used to access the wound healing potential of TA-modified and unmodified AgNPs. Results: TA-modified but not unmodified AgNPs exhibited effective antibacterial activity against Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli and stimulated migration of keratinocytes in vitro. The tests using the mouse splint wound model showed that TA-modified 33 and 46 nm AgNPs promoted better wound closure, epithelialization, angiogenesis and formation of the granulation tissue. Additionally, AgNPs elicited expression of VEGF-α, PDGF-β and TGF-β1 cytokines involved in wound healing more efficiently in comparison to control and TA-treated wounds. However, both the lymph node assay and the wound model showed that TA-modified AgNPs sized 13 nm can elicit strong inflammatory response not only during wound healing but also when applied to the damaged skin. Conclusion: TA-modified AgNPs sized >26 nm promote wound healing better than TA-modified or unmodified AgNPs. These findings suggest that TA-modified AgNPs sized >26 nm may have a promising application in wound management.

Diabetes and obesity are diseases characterized by their increasing incidence every year. When comparing with healthy subjects, the serum levels of chromium (Cr) are lowered in these two diseases. Several studies conducted in laboratory animals with experimentally- induced diabetes demonstrated that supplementation with chromium ions (III) decreased glucose concentration in the blood, reduced the probability of atherosclerosis and heart attack, lowered the levels of cholesterol and low density lipoprotein (LDL). The Importance of chromium is actually challenged due to lack of clear manifestations of Cr deficiency in humans and animals. The aim of this review was to present current knowledge about Cr its role in the organism and possible mechanisms of its action also in metabolic disorders such as diabetes or obesity. In the last decade, Cr was established to be rather a beneficial than essential trace element in mammals, and has gained popularity as a nutritional supplement and a component of many multivitamin/mineral formulations, fortified food and energy drinks. Cr supplements are widespread for diabetes and obesity treatment, despite conflicting reports on its efficacy. It was suggested that Cr shows a beneficial influence upon glucose and lipid disturbances. The recent clinical trials provided evidence both in favor and against the importance of Cr in healthy and ill organisms. Unfortunately, also the molecular mechanism by which chromium affects glucose and lipid metabolism is still unclear. Beneficial effects of diet supplementation with different sources of Cr³⁺ can be potentially explained by rather pharmacological than nutritional effects.

(1) Background: Tannic acid is a plant-derived polyphenol showing antiviral activity mainly because of an interference with the viral adsorption. In this work, we tested whether the modification of silver nanoparticles with tannic acid (TA-AgNPs) can provide a microbicide with additional adjuvant properties to treat genital herpes infection. (2) Methods: The mouse model of the vaginal herpes simplex virus 2 (HSV-2) infection was used to test immune responses after treatment of the primary infection with TA-AgNPs, and later, after a re-challenge with the virus. (3) Results: The mice treated intravaginally with TA-AgNPs showed better clinical scores and lower virus titers in the vaginal tissues soon after treatment. Following a re-challenge, the vaginal tissues treated with TA-AgNPs showed a significant increase in the percentages of IFN-gamma+ CD8+ T-cells, activated B cells, and plasma cells, while the spleens contained significantly higher percentages of IFN-gamma+ NK cells and effector-memory CD8+ T cells in comparison to NaCl-treated group. TA-AgNPs-treated animals also showed significantly better titers of anti-HSV-2 neutralization antibodies in sera; and (4) Conclusions: Our findings suggest that TA-AgNPs sized 33 nm can be an effective anti-viral microbicide to be applied upon the mucosal tissues with additional adjuvant properties enhancing an anti-HSV-2 immune response following secondary challenge.

Objective: Elevated levels of interleukin (IL)-7 are present in the blood of HIV-positive patients and it is known that IL-7 receptor (IL-7R)α expression decreases on T cells during HIV infection. The subset(s) of T cells with low IL-7Rα and the consequence of low IL-7Rα expression for T-cell survival are poorly characterized. Design: The frequency of IL-7Rα-negative T cells in HIV-positive patients was studied in relation to CD4 T-cell counts, IL-7 concentration and survival in culture. We analysed IL-7Rα expression in different T-cell populations and in relation to Bcl-2 expression. Methods: Specimens from 38 HIV-1 patients and 17 controls were examined. IL-7Rα and Bcl-2 expression in different T-cell populations was studied by flow cytometry. The influence of IL-7Rα expression on T-cell survival was studied by culturing T cells in the presence of IL-7. Results: Down-regulation of IL-7Rα on T cells correlated with depletion of CD4 T cells (P < 0.001) and also with increased concentration of serum IL-7 (P < 0.05). The decreased IL-7Rα expression was associated with low Bcl-2 expression and with the reduced survival capacity of T cells in the presence of IL-7 in vitro. Particularly, T cells with memory phenotype showed a decreased IL-7Rα expression in association with CD28 down-regulation. Conclusions: The positive effects of IL-7 on survival and homeostatic proliferation of T cells might be severely impaired in HIV-infected individuals due to IL-7Rα down-regulation. Differentiation towards a CD28-negative memory phenotype in response to chronic activation may lead to an overall decrease of IL-7 mediated survival within the peripheral T-cell pool.