Chronic periodontitis (ChP) is a multifactorial disease influenced by microbial and host genetic variability; however, the role of beta-defensin-2 genomic (DEFB4) copy number (CN) variation (V) in ChP remains unknown. The association of the occurrence and severity of ChP and DEFB4 CNV was analyzed. Our study included 227 unrelated Caucasians, that is, 136 ChP patients (combined ChP) and 91 control individuals. The combined ChP group was subdivided into the severe ChP and slight-to-moderate ChP subgroups. To determine DEFB4 CNV, we isolated genomic DNA samples and analyzed them by relative quantitation using the comparative CT method. The serum beta-defensin-2 (hBD-2) level was determined via ELISA. The distribution pattern and mean DEFB4 CN did not differ significantly in combined ChP cases vs. the controls; however, the mean DEFB4 CN in the severe ChP group differed significantly from those for the control and slight-to-moderate ChP groups. Low DEFB4 CN increased the risk of severe ChP by about 3-fold. DEFB4 CN was inversely associated with average attachment loss. Mean serum hBD-2 levels were highest in the controls, followed by the slight-to-moderate ChP group and the severe ChP group. The results suggested an association between decreased DEFB4 CN and serum hBD-2 levels and periodontitis severity.

Dermatophytes initiate dermatophytosis, but susceptibility to infection is dictated by host genetic factors, although the role of some of these-such as human beta-defensin 2 (hBD-2) genomic (DEFB4) copy number (CN) variation and its induction by IL-22-remains unclear. This was investigated in this cross-sectional study in 442 unrelated Caucasian subjects, including 195 healthy controls and 247 dermatophytosis patients who were divided into five subgroups according to clinical presentation. DNA samples were evaluated for DEFB4 CN variation by relative quantification using the comparative CT method, and serum hBD-2 and IL-22 levels were determined by ELISA. DEFB4 CN in patients was significantly lower and, except in the tinea cruris subgroup, serum hBD-2 levels were higher than in controls. The positive correlation between hBD-2 levels and DEFB4 CN observed in controls was not detected in patients, who also had higher serum IL-22 levels that were positively correlated with hBD-2 levels. Moreover, unlike in control subjects, the serum IL-22 level was negatively correlated with DEFB4 CN in patients. Taken together, these findings suggest an association between decreased DEFB4 CN, elevated serum hBD-2 and IL-22 levels, and dermatophytosis, underscoring a gene/cytokine interaction in the occurrence of this infection.

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There is still a need for improving the treatment of breast cancer with doxorubicin (DOX). In this paper, we functionalized magnetic nanoparticles (MNPs) with DOX and studied the DOX-induced antitumor effects in breast cancer cells (BT474) in the presence of magnetic hyperthermia (43 °C, 1 h). We show that i) intratumoral application of DOX-functionalized MNPs (at least at a concentration of 9.6 nmol DOX/100 mm3 tumor volume) combined with magnetic hyperthermia favors tumor regression in vivo, and there is evidence for an increased effect compared to magnetic hyperthermia alone or to the intratumoral application of free DOX and ii) the presence of the pseudopeptide NucAnt (N6L) on the MNP surface might well be beneficial in its function as carrier for MNP internalization into breast cancer cells in vitro, which could further augment the possibility of the induction of intracellular heating spots and cell death in the future.

Background and purpose:The biogenic amine, histamine plays a pathophysiological regulatory role in cellular processes of a variety of immune cells. This work analyses the actions of histamine on gd-T lymphocytes, isolated from human peripheral blood, which are critically involved in immunological surveillance of tumours. Experimental approach: We have analysed effects of histamine on the intracellular calcium, actin reorganization, migratory response and the interaction of human gd T cells with tumour cells such as the A2058 human melanoma cell line, the human Burkitt's Non-Hodgkin lymphoma cell line Raji, the T-lymphoblastic lymphoma cell line Jurkat and the natural killer cell-sensitive erythroleukaemia cell line, K562. Key results: gd T lymphocytes express mRNA for different histamine receptor subtypes. In human peripheral blood gd T cells, histamine stimulated Pertussis toxin-sensitive intracellular calcium increase, actin polymerization and chemotaxis. However, histamine inhibited the spontaneous cytolytic activity of gd T cells towards several tumour cell lines in a cholera toxin-sensitive manner. A histamine H4 receptor antagonist abolished the histamine induced gd T cell migratory response. A histamine H2 receptor agonist inhibited gd T cell-mediated cytotoxicity. Conclusions and implications:Histamine activated signalling pathways typical of chemotaxis (Gi protein-dependent actin reorganization, increase of intracellular calcium) and induced migratory responses in gd T lymphocytes, via the H4 receptor, whereas it down-regulated gd T cell mediated cytotoxicity through H2 receptors and Gs protein-coupled signalling. Our data suggest that histamine activated gd T cells could modulate immunological surveillance of tumour tissue. Linked articles:This article is part of a themed section on Analytical Receptor Pharmacology in Drug Discovery. To view the other articles in this section visit http://dx

Doxorubicin (DOX) is a frequently used chemotherapeutic drug for breast cancer, but its site specificity and local internalization into tumor cells is rather low. In this paper we conjugated magnetic nanoparticles (MNPs) with DOX and/or a pseudopeptide NucAnt (N6L) as modality to enhance DOX-induced antitumor effects in breast cancer cells (BT474). In this context, we determined cellular uptake of MNP formulations, analyzed cell viability and expression of apoptotic and cell cycle proteins after magnetic hyperthermia (43°C, 1 h) in vivo and in vitro. We have shown that i) the presence of N6L on the surface of DOX-functionalized MNPs increases their internalization into a target cells and potentiates the cytotoxic potential of the anticancer drug, ii) in combination with hyperthermia, DOX functionalized MNPs influence the expression of apoptotic and cell cycle proteins, and also favors tumor regression in vivo. Our data show that intratumoral application of DOX coupled MNPs is able to overcome biological barriers to chemotherapeutic drugs, enabling them to penetrate into the target cells. Combined with hyperthermia these MNPs can be an effective method in enhancing the localised delivery and penetration of DOX into breast cancer cells.