Complications of Teeth Affected by Molar-Incisor Malformation and Pathogenesis According to Microbiome Analysis

A molar-incisor malformation (MIM) is a recently reported dental anomaly that causes premature loss of the first molar with severe dentoalveolar infection. However, there has been no research on the pathogenesis yet. The aim of this study was to report the clinical process of MIMs and investigate the pathogenesis by conducting a microbiome analysis. An eight-year-old girl was diagnosed with MIM and after two years, four permanent first molars were sequentially extracted due to severe dentoalveolar infection. We recorded the patient`s clinical progress and collected oral microbiome samples from the extracted teeth with MIM and sound teeth as controls. The sites of microbiome sampling were represented by five habitats in two groups. Group (1) was the perio group: ① supragingival plaque, ② subgingival plaque, and ③ a pical abscess; and group (2) was the endo group: ④ coronal pulp chamber and ⑤ root canal. The perio group was composed predominantly of genera Streptococcus, Veilonella, and Leptotrichia. Spirochetes appeared in one sample from a severe periodontal abscess. Aggregatibacter actinomyces were not identified. In the endo groups, pulp necrosis was observed in all MIM and the genera Peptostreptococcus and Parvimonas predominated. In conclusion, MIM teeth caused localized tooth-related periodontitis with pulp necrosis rather than localized juvenile periodontitis, resulting in a poor prognosis, and timely extraction is highly recommended.

Potential role of diacylglycerol kinases in immune-mediated diseases

The mechanism promoting exacerbated immune responses in allergy and autoimmunity as well as those blunting the immune control of cancer cells are of primary interest in medicine. Diacylglycerol kinases (DGKs) are key modulators of signal transduction, which blunt diacylglycerol (DAG) signals and produce phosphatidic acid (PA). By modulating lipid second messengers, DGK modulate the activity of downstream signaling proteins, vesicle trafficking and membrane shape. The biological role of the DGK α and ζ isoforms in immune cells differentiation and effector function was subjected to in deep investigations. DGK α and ζ resulted in negatively regulating synergistic way basal and receptor induced DAG signals in T cells as well as leukocytes. In this way, they contributed to keep under control the immune response but also downmodulate immune response against tumors. Alteration in DGKα activity is also implicated in the pathogenesis of genetic perturbations of the immune function such as the X-linked lymphoproliferative disease 1 and localized juvenile periodontitis. These findings suggested a participation of DGK to the pathogenetic mechanisms underlying several immune-mediated diseases and prompted several researches aiming to target DGK with pharmacologic and molecular strategies. Those findings are discussed inhere together with experimental applications in tumors as well as in other immune-mediated diseases such as asthma.

Aggregatibacter, a Low Abundance Pathobiont That Influences Biogeography, Microbial Dysbiosis, and Host Defense Capabilities in Periodontitis: The History of a Bug, and Localization of Disease

Aggregatibacter actinomycetemcomitans, the focus of this review, was initially proposed as a microbe directly related to a phenotypically distinct form of periodontitis called localized juvenile periodontitis. At the time, it seemed as if specific microbes were implicated as the cause of distinct forms of disease. Over the years, much has changed. The sense that specific microbes relate to distinct forms of disease has been challenged, as has the sense that distinct forms of periodontitis exist. This review consists of two components. The first part is presented as a detective story where we attempt to determine what role, if any, Aggregatibacter plays as a participant in disease. The second part describes landscape ecology in the context of how the host environment shapes the framework of local microbial dysbiosis. We then conjecture as to how the local host response may limit the damage caused by pathobionts. We propose that the host may overcome the constant barrage of a dysbiotic microbiota by confining it to a local tooth site. We conclude speculating that the host response can confine local damage by restricting bacteremic translocation of members of the oral microbiota to distant organs thus constraining morbidity and mortality of the host.

One of Two Human Lactoferrin Variants Exhibits Increased Antibacterial and Transcriptional Activation Activities and Is Associated with Localized Juvenile Periodontitis

ABSTRACT The iron-binding protein lactoferrin is a ubiquitous and abundant constituent of human exocrine secretions. Lactoferrin inhibits bacterial growth by sequestering essential iron and also exhibits non-iron-dependent antibacterial, antifungal, antiviral, antitumor, anti-inflammatory, and immunoregulatory activities. All of these non-iron-dependent activities are mediated by the highly charged N terminus of lactoferrin. In this study we characterized a Lys/Arg polymorphism at position 29 in the N-terminal region of human lactoferrin that results from a single nucleotide polymorphism in exon 1 of the human lactoferrin gene. We expressed cDNAs encoding both lactoferrin variants in insect cells and purified the two proteins by ion exchange chromatography. The two lactoferrin variants exhibited nearly identical iron-binding and iron-releasing activities and equivalent bactericidal activities against a strain of the gram-negative bacterium Actinobacillus actinomycetemcomitans. When tested against the gram-positive species Streptococcus mutans and Streptococcus mitis, however, lactoferrin containing Lys at position 29 exhibited significantly greater bactericidal activity than did lactoferrin containing Arg. In addition, the Lys-containing lactoferrin stimulated bovine tracheal epithelial cells to synthesize much higher levels of tracheal antimicrobial peptide mRNA than did the Arg-containing variant. A genotyping assay that distinguished between the two alleles based on a polymorphic EarI restriction site showed that the Lys and Arg alleles had frequencies of 24% and 76%, respectively, among 17 healthy human subjects, and 72% and 28%, respectively, among nine patients with localized juvenile periodontitis. Our findings suggest that these two lactoferrin variants are functionally different and that these differences may contribute to the pathogenesis of localized juvenile periodontitis.