A CD8+ T cell immune evasion protein specific to Epstein-Barr virus and its close relatives in Old World primates

gamma 1-Herpesviruses such as Epstein-Barr virus (EBV) have a unique ability to amplify virus loads in vivo through latent growth-transforming infection. Whether they, like alpha- and beta-herpesviruses, have been driven to actively evade immune detection of replicative (lytic) infection remains a moot point. We were prompted to readdress this question by recent work (Pudney, V.A., A.M. Leese, A.B. Rickinson, and A.D. Hislop. 2005. J. Exp. Med. 201:349-360; Ressing, M.E., S.E. Keating, D. van Leeuwen, D. Koppers-Lalic, I.Y. Pappworth, E.J.H.J. Wiertz, and M. Rowe. 2005. J. Immunol. 174:6829-6838) showing that, as EBV-infected cells move through the lytic cycle, their susceptibility to EBV-specific CD8(+) T cell recognition falls dramatically, concomitant with a reductions in transporter associated with antigen processing (TAP) function and surface human histocompatibility leukocyte antigen (HLA) class I expression. Screening of genes that are unique to EBV and closely related gamma 1-herpesviruses of Old World primates identified an early EBV lytic cycle gene, BNLF2a, which efficiently blocks antigen-specific CD8(+) T cell recognition through HLA-A-, HLA-B-, and HLA-C-restricting alleles when expressed in target cells in vitro. The small (60-amino acid) BNLF2a protein mediated its effects through interacting with the TAP complex and inhibiting both its peptide- and ATP-binding functions. Furthermore, this targeting of the major histocompatibility complex class I pathway appears to be conserved among the BNLF2a homologues of Old World primate gamma 1-herpesviruses. Thus, even the acquisition of latent cycle genes endowing unique growth-transforming ability has not liberated these agents from evolutionary pressure to evade CD8(+) T cell control over virus replicative foci.     

Incorporation of Copper-Doped Mesoporous Bioactive Glass Nanospheres in Experimental Dental Composites: Chemical and Mechanical Characterization

Experimental dental resin composites incorporating copper-doped mesoporous bioactive glass nanospheres (Cu-MBGN) were designed to impart antibacterial and remineralizing properties. The study evaluated the influence of Cu-MBGN on the mechanical properties and photopolymerization of resin composites. Cu-MBGN were synthesized using a microemulsion-assisted sol–gel method. Increasing amounts of Cu-MBGN (0, 1, 5, and 10 wt %) were added to the organic polymer matrix with inert glass micro- and nanofillers while maintaining a constant resin/filler ratio. Six tests were performed: X-ray diffraction, scanning electron microscopy, flexural strength (FS), flexural modulus (FM), Vickers microhardness (MH), and degree of conversion (DC). FS and MH of Cu-MBGN composites with silica fillers showed no deterioration with aging, with statistically similar results at 1 and 28 days. FM was not influenced by the addition of Cu-MBGN but was reduced for all tested materials after 28 days. The specimens with 1 and 5% Cu-MBGN had the highest FS, FM, MH, and DC values at 28 days, while controls with 45S5 bioactive glass had the lowest FM, FS, and MH. DC was high for all materials (83.7–93.0%). Cu-MBGN composites with silica have a potential for clinical implementation due to high DC and good mechanical properties with adequate resistance to aging.     

NMR insights on nano silver post-surgical treatment of superficial caseous lymphadenitis in small ruminants

Caseous lymphadenitis (CL), caused by a pathogen of the second class of biosafety – Corynebacterium pseudotuberculosis, is a chronic and severe infectious disease that affects small ruminants and requires long, ineffective treatment which generally leads to animal sacrifice so as to stop the disease spreading. The infected animals suffer the excision of affected superficial lymph nodes and post-surgical treatment with iodine (10% solution in ethanol) and, sometimes, prolonged antibiotic use, but only if the sick animals are of great importance to breeding. Herein, we propose a cheap and easy to apply treatment of CL with excellent results using biogenic silver nanoparticles (AgNP) based technology. AgNP antibacterial properties were investigated in vitro against Corynebacterium pseudotuberculosis cells and in vivo on small ruminants with CL. Treatment of surgical wounds resulting from the excision of superficial CL lesions with a AgNP-based cream was compared to the standard post-surgical treatment method by iodine. Also, the effects of AgNP-based cream treatment were evaluated and compared with the effects of the iodine CL treatment by serum NMR-based metabolomics. Serum samples were collected from 29 animals, 9 sheep and 20 goats, during the treatments and analyzed. All animals showed stable serum metabolomes when iodine or AgNP-based cream effects were compared. The AgNP-based cream treatment showed excellent results, especially in accelerating the healing of wounds, which occurred two to three times faster in comparison with the iodine treatment. AgNP-based cream treatment also prevented CL reappearance and did not cause any side effects on animals. This is the first report on very effective post-surgical treatment of superficial CL in small ruminants based on biogenic silver nanoparticles, which might open up the possibility for a safe veterinary application of AgNP-based cream.

Biogenic nanosilver in a pharmaceutical cream for wound healing in animal and human healthcare.     

Mineralocorticoid receptor and heat shock protein expression levels in peripheral lymphocytes from war trauma-exposed men with and without PTSD

Alterations in the number and functional status of mineralocorticoid (MR) and glucocorticoid receptors (GR) may contribute to vulnerability to posttraumatic stress disorder (PTSD). Corticosteroid receptors are chaperoned by heat shock proteins Hsp90 and Hsp70. We examined relations between corticosteroid receptor and heat shock protein expression levels, and related them with war trauma exposure, PTSD and resilience to PTSD. Relative levels of MR, Hsp90 and Hsp70 were determined by immunoblotting in lymphocytes from war trauma-exposed men with current PTSD (current PTSD group, n=113), with life-time PTSD (life-time PTSD group, n=61) and without PTSD (trauma control group, n=88), and from non-traumatized healthy controls (healthy control group, n=85). Between-group differences in MR, Hsp90 and Hsp70 levels and in MR/GR ratio were not observed. The level of MR was correlated with both Hsp90 and Hsp70 levels in trauma control and healthy control groups. On the other hand, GR level was correlated only with Hsp90 level, and this correlation was evident in current PTSD and trauma control groups. In conclusion, PTSD and exposure to trauma are not related to changes in lymphocyte MR, Hsp90 or Hsp70 levels, but may be associated with disturbances in corticosteroid receptors interaction with heat shock proteins.     

Genotoxicity in gingival cells of patients undergoing tooth restoration with two different dental composite materials

Objectives

Dental composite materials come into direct contact with oral tissue, especially gingival cells. This study was performed to evaluate possible DNA damage to gingival cells exposed to resin composite dental materials.

Materials and methods

Class V restorations were placed in 30 adult patients using two different composite resins. The epithelial cells of the gingival area along the composite restoration were sampled prior to and after 7, 30, and 180 days following the restoration of the tooth. DNA damage was analysed by comet and micronucleus assays in gingival exfoliated epithelial cells.

Results

The results showed significantly higher comet assay parameters (tail length and % DNA in the tail) within periods of 30 and 180 days. The micronucleus test for the same exposure time demonstrated a higher number of cells with micronuclei, karyolysis, and nuclear buds. Results did not reveal any difference between the two composite materials for the same duration of exposure.

Conclusion

Based on the results, we can conclude that the use of composite resins causes cellular damage. As dental composite resins remain in intimate contact with oral tissue over a long period of time, further research on their possible genotoxicity is advisable.

Clinical relevance

Long-term exposure of gingival cells to two different composite materials demonstrated certain DNA damage. However, considering the significant decline in micronuclei frequency after 180 days and efficiency in the repair of primary DNA damage, the observed effects could not be indicated as biologically relevant.     

In vivo toxicity evaluation of two polyoxotungstates with potential antidiabetic activity using Wistar rats as a model system

In this study, the in vivo hypoglycemic effect of a donut-shaped polyanion salt (NH₄)₁₄[Na@P₅W₃₀O₁₁₀]·31H₂O {NaP₅W₃₀} and its Ag-containing derivative K₁₄[Ag@P₅W₃₀O₁₁₀]·22H₂O·6KCl {AgP₅W₃₀}, as well as their hepatotoxicity and nephrotoxicity, was evaluated. In the screening hypoglycemic study, Wistar albino rats with streptozotocin induced diabetes were treated intraperitoneally with three single doses (5, 10, and 20 mg per kg per b.w.) of both investigated polyoxotungstates. The blood glucose levels, measured before and after 2, 4 and 6 h polyoxotungstate application, showed that both studied compounds induced the most pronounced and time dependent glucose lowering effects at the doses of 20 mg kg⁻¹. Thus, daily doses of 20 mg kg⁻¹ were administered to Wistar albino rats orally for 14 days in further toxicity examinations. The serum glucose concentration and biochemical parameters of kidney and liver function, as well as a histopathological analysis of kidney and liver tissues were evaluated 14 days after the polyoxotungstate administration. Both investigated compounds did not induce statistically significant alterations of the serum glucose and uric acid concentrations, as well as some of the liver function markers (serum alanine and aspartate aminotransferases, and alkaline phosphatase activities). However, the significant decrease in serum total protein and albumin concentrations and the increase in biochemical parameters of renal function – serum urea (up to 63.1%) and creatinine concentrations (up to 23.3%) were observed for both polyoxotungstates. In addition, the detected biochemical changes were in accordance with kidney and liver histhopathological analysis. Accordingly, the hepatotoxic and nephrotoxic effects of these potential antidiabetic polyoxotungstates could be considered as mild.

Study of the in vivo hypoglycemic effect, hepatotoxicity and nephrotoxicity of a donut-shaped polyanion salt (NH₄)₁₄[Na@P₅W₃₀O₁₁₀]·31H₂O {NaP₅W₃₀} and its Ag-containing derivative K₁₄[Ag@P₅W₃₀O₁₁₀]·22H₂O·6KCl {AgP₅W₃₀}.     

Central nervous system-infiltrated immune cells induce calcium increase in astrocytes via astroglial purinergic signaling

Interaction between autoreactive immune cells and astroglia is an important part of the pathologic processes that fuel neurodegeneration in multiple sclerosis. In this inflammatory disease, immune cells enter into the central nervous system (CNS) and they spread through CNS parenchyma, but the impact of these autoreactive immune cells on the activity pattern of astrocytes has not been defined. By exploiting naïve astrocytes in culture and CNS-infiltrated immune cells (CNS IICs) isolated from rat with experimental autoimmune encephalomyelitis (EAE), here we demonstrate previously unrecognized properties of immune cell–astrocyte interaction. We show that CNS IICs but not the peripheral immune cell application, evokes a rapid and vigorous intracellular Ca²⁺ increase in astrocytes by promoting glial release of ATP. ATP propagated Ca²⁺ elevation through glial purinergic P2X7 receptor activation by the hemichannel-dependent nucleotide release mechanism. Astrocyte Ca²⁺ increase is specifically triggered by the autoreactive CD4⁺ T-cell application and these two cell types exhibit close spatial interaction in EAE. Therefore, Ca²⁺ signals may mediate a rapid astroglial response to the autoreactive immune cells in their local environment. This property of immune cell–astrocyte interaction may be important to consider in studies interrogating CNS autoimmune disease.     

Clinical utility of stem cells for periodontal regeneration

The aim of this review is to discuss the clinical utility of stem cells in periodontal regeneration by reviewing relevant literature that assesses the periodontal-regenerative potential of stem cells. We considered and described the main stem cell populations that have been utilized with regard to periodontal regeneration, including bone marrow-derived mesenchymal stem cells and the main dental-derived mesenchymal stem cell populations: periodontal ligament stem cells, dental pulp stem cells, stem cells from human exfoliated deciduous teeth, stem cells from apical papilla and dental follicle precursor cells. Research into the use of stem cells for tissue regeneration has the potential to significantly influence periodontal treatment strategies in the future.