Aim:To cross-sectionally analyse the submucosal microbiome of peri-implantitis (PI) lesions at different severity levels. Materials and Methods:Microbial signatures of 45 submucosal plaque samples from untreated PI lesions obtained from 30 non-smoking, systemically healthy subjects were assessed by 16s sequencing. Linear mixed models were used to identify taxa with differential abundance by probing depth, after correction for age, gender, and multiple samples per subject. Network analyses were performed to identify groups of taxa with mutual occurrence or exclusion. Subsequently, the effects of periimplant probing depth on submucosal microbial dysbiosis were calculated using the microbial dysbiosis index. Results:In total, we identified 337 different taxa in the submucosal microbiome of PI.Total abundance of 12 taxa correlated significantly with increasing probing depth; a significant relationship with lower probing depth was found for 16 taxa. Network analysis identified two mutually exclusive complexes associated with shallow | 1499 KRÖGER Et al.

Microglial activation plays an integral role in the development and course of neurodegeneration. Although neuropeptides such as bradykinin (BK), somatostatin (SST), and endothelin (ET) are known to be important mediators of inflammation in the periphery, evidence of a similar function in brain is scarce. Using immunocytochemistry, we demonstrate the expression of receptors for BK (B1, B2 subtypes), ET (ETA, ETB subtypes) and SST (SST 2, 3, 4 subtypes) in primary microglia and microglial cell lines. Exposure of BV2 and N9, as well as primary microglial cells to BK or SST increased Aβ uptake in a concentration-dependent manner, whereas endothelin decreased Aβ uptake. This was caused by increased phagocytosis of Aβ since the rate of intracellular Aβ degradation remained unaffected. All neuropeptides increased chemotactic activity of microglia. In addition, BK reduced Aβ-induced expression of proinflammatory genes including iNOS and COX-2. ET decreased the Aβ-induced expression of monocyte chemoattractant protein 1 and interleukin-6. These results suggest that neuropeptides play an important role in chemotaxis and Aβ clearance and modulate the brain's response to neuroinflammatory processes.

Nitric oxide has been implicated in the regulation of enzyme activity, particularly the activity of metalloproteinases. Since the inducible form of the nitric oxide synthase (NOS2), is upregulated in Alzheimer's disease, we investigated the activity of two amyloid β degrading enzymes, IDE and neprilysin. In vitro we demonstrated that the activity of IDE was inhibited by *NO donor Sin-1, whereas activity of neprilysin remained unaffected. In vivo the activity of insulin-degrading enzyme was lowered in APP/PS1 mice, but not in APP/PS1/NOS2(-/-) mice. These data suggest that NOS2 upregulation impairs amyloid β degradation through negative regulation of IDE activity and thus loss of NOS2 activity will positively influence amyloid β clearance.

Omics analyses, including the systematic cataloging of messenger RNA and microRNA sequences or DNA methylation patterns in a cell population, organ or tissue sample, are powerful means of generating comprehensive genome-level data sets on complex diseases. We have systematically assessed the transcriptome, miRNome and methylome of gingival tissues from subjects with different diagnostic entities of periodontal disease, and studied the transcriptome of primary cells ex vivo, or in vitro after infection with periodontal pathogens. Our data further our understanding of the pathobiology of periodontal diseases and indicate that the gingival -omes translate into discernible phenotypic characteristics and possibly support an alternative, "molecular" classification of periodontitis.Here, we outline the laboratory steps required for the processing of periodontal cells and tissues for -omics analyses using current microarrays or next-generation sequencing technology.