Within the same subjects, putative periodontal pathogens were common to both periodontal and peri-implant sites irrespective of health status. The prevalence and levels of P. gingivalis and F. nucleatum were significantly associated with periodontitis, but not with peri-implantitis. A. actinomycetemcomitans was associated with both disease conditions, periodontitis and peri-implantitis, but not with either gingival or mucosal health.

Changes in the enzymatic activity of protein arginine methyltransferase (PRMT) 5 have been associated with cancer; however, the protein's role in acute myeloid leukemia (AML) has not been fully evaluated. Here, we show that increased PRMT5 activity enhanced AML growth in vitro and in vivo while PRMT5 downregulation reduced it. In AML cells, PRMT5 interacted with Sp1 in a transcription repressor complex and silenced miR-29b preferentially via dimethylation of histone 4 arginine residue H4R3. As Sp1 is also a bona fide target of miR-29b, the miR silencing resulted in increased Sp1. This event in turn led to transcription activation of FLT3, a gene that encodes a receptor tyrosine kinase. Inhibition of PRMT5 via sh/siRNA or a first-in-class small-molecule inhibitor (HLCL-61) resulted in significantly increased expression of miR-29b and consequent suppression of Sp1 and FLT3 in AML cells. As a result, significant antileukemic activity was achieved. Collectively, our data support a novel leukemogenic mechanism in AML where PRMT5 mediates both silencing and transcription of genes that participate in a 'yin-yang' functional network supporting leukemia growth. As FLT3 is often mutated in AML and pharmacologic inhibition of PRMT5 appears feasible, the PRMT5-miR-29b-FLT3 network should be further explored as a novel therapeutic target for AML.

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Objective: Periodontitis and peri-implantitis are oral infectious-inflammatory diseases that share similarities in their pathology and etiology. Our objective was to characterize the single-site subgingival and submucosal microbiomes of implant-rehabilitated, partially dentate Chinese subjects (n = 18) presenting with both periodontitis and peri-implantitis. Materials and methods:Subgingival/submucosal plaque samples were collected from four clinically distinct sites in each subject: peri-implantitis submucosa (DI), periodontal pocket (DT), clinically healthy (unaffected) peri-implant submucosa (HI), and clinically healthy (unaffected) subgingival sulcus (HT). The bacterial microbiota present was analyzed using Illumina MiSeq sequencing.Results: Twenty-six phyla and 5,726 operational taxonomic units (OTUs, 97% sequence similarity cutoff) were identified. Firmicutes, Proteobacteria, Fusobacteria, Bacteroidetes, Actinobacteria, Synergistetes, TM7, and Spirochaetes comprised 99.6% of the total reads detected. Bacterial communities within the DI, DT, HI, and HT sites shared high levels of taxonomic similarity. Thirty-one "core species" were present in >90% sites, with Streptococcus infantis/mitis/oralis (HMT-070/HMT-071/ HMT-638/HMT-677) and Fusobacterium sp. HMT-203/HMT-698 being particularly prevalent and abundant. Beta-diversity analyses (PERMANOVA test, weighted UniFrac) revealed the largest variance in the microbiota was at the subject level (46%), followed by periodontal health status (4%). Differing sets of OTUs were associated with periodontitis and peri-implantitis sites, respectively. This included putative "periodontopathogens," such as Prevotella, Porphyromonas, Tannerella, Bacteroidetes [G-5], and Treponema spp. Interaction network analysis identified several putative patterns underlying dysbiosis in periodontitis/peri-implantitis sites. Conclusions: Species (OTU) composition of the periodontal and peri-implant microbiota varied widely between subjects. The inter-subject variations in subgingival/ submucosal microbiome composition outweighed differences observed between implant vs. tooth sites, or between diseased vs. healthy (unaffected) peri-implant/ periodontal sites. | 761 YU et al. vincentii ("Fusobacterium Genus Probe 2"). Our data also correlate with that reported by Maruyama et al. (2014), who found that F. nucleatum, S. oralis, and Neisseria subflava, were abundant in both periodontitis and peri-implantitis lesions sampled from the same Japanese individuals. The respective compositions of the "core" microbiota reported in several other high-throughput TA B L E 3 Bacterial taxa present at higher abundances in the four respective clinical sites a Clinically healthy (unaffected) periodontal sites (HT) Periodontitis sites (DT) Halomonas sp. (OTU0) (core) Tannerella forsythia HMT-613 (OTU15) Escherichia coli HMT-574 (OTU17) Cardiobacterium valvalum HMT-540 (OTU33) Streptococcus mutans HMT-686 (OTU27) Capnocytophaga granulosa (OTU32) Veillonella dispar HMT-160 (OTU1252) Bacteroidales [G-2] sp. HMT-274...