Research on Graphene and Its Derivatives in Oral Disease Treatment.

Oral diseases present a global public health problem that imposes heavy financial burdens on individuals and health-care systems. Most oral health conditions can be treated in their early stage. Even if the early symptoms of oral diseases do not seem to cause significant discomfort, prompt treatment is essential for preventing their progression. Biomaterials with superior properties enable dental therapies with applications in restoration, therapeutic drug/protein delivery, and tissue regeneration. Graphene nanomaterials have many unique mechanical and physiochemical properties and can respond to the complex oral microenvironment, which includes oral microbiota colonization and high masticatory force. Research on graphene nanomaterials in dentistry, especially in caries, periodontitis therapy, and implant coatings, is progressing rapidly. Here, we review the development of graphene and its derivatives for dental disease therapy.

Porphyromonas gingivalis Induces Increases in Branched-Chain Amino Acid Levels and Exacerbates Liver Injury Through livh/livk.

Porphyromonas gingivalis, a keystone periodontal pathogen, has emerged as a risk factor for systemic chronic diseases, including non-alcoholic fatty liver disease (NAFLD). To clarify the mechanism by which this pathogen induces such diseases, we simultaneously analyzed the transcriptome of intracellular P. gingivalis and infected host cells via dual RNA sequencing. Pathway analysis was also performed to determine the differentially expressed genes in the infected cells. Further, the infection-induced notable expression of P. gingivalis livk and livh genes, which participate in branched-chain amino acid (BCAA) transfer, was also analyzed. Furthermore, given that the results of recent studies have associated NAFLD progression with elevated serum BCAA levels, which reportedly, are upregulated by P. gingivalis, we hypothesized that this pathogen may induce increases in serum BCAA levels and exacerbate liver injury via livh/livk. To verify this hypothesis, we constructed P. gingivalis livh/livk-deficient strains (Δlivk, Δlivh) and established a high-fat diet (HFD)-fed murine model infected with P. gingivalis. Thereafter, the kinetic growth and exopolysaccharide (EPS) production rates as well as the invasion efficiency and in vivo colonization of the mutant strains were compared with those of the parental strain. The serum BCAA and fasting glucose levels of the mice infected with either the wild-type or mutant strains, as well as their liver function were also further investigated. It was observed that P. gingivalis infection enhanced serum BCAA levels and aggravated liver injury in the HFD-fed mice. Additionally, livh deletion had no effect on bacterial growth, EPS production, invasion efficiency, and in vivo colonization, whereas the Δlivk strain showed a slight decrease in invasion efficiency and in vivo colonization. More importantly, however, both the Δlivk and Δlivh strains showed impaired ability to upregulate serum BCAA levels or exacerbate liver injury in HFD-fed mice. Overall, these results suggested that P. gingivalis possibly aggravates NAFLD progression in HFD-fed mice by increasing serum BCAA levels, and this effect showed dependency on the bacterial BCAA transport system.

Global, regional, and national burden of periodontitis from 1990 to 2019: Results from the Global Burden of Disease study 2019.

BACKGROUND: To evaluate the prevalence and incidence of periodontitis and associated disability-adjusted life years (DALYs) from 1990 to 2019. METHODS: We collected data on periodontitis between 1990 and 2019 from the Global Burden of Disease (GBD) 2019 Study. The global prevalence, incidence, and DALYs attributed to periodontitis were analyzed. The age-standardized rate (ASR) and estimated annual percentage changes (EAPCs) were calculated to quantify the burden of the disease and temporal trends. RESULTS: The ASR of the prevalence, incidence, and DALYs increased worldwide from 1990 to 2019. In 2019, Western Sub-Saharan Africa carried the heaviest burden of periodontitis, whereas the nation with the highest periodontitis burden was Gambia. The burden of periodontitis was negatively associated with the level of socioeconomic development. Although, the majority of periodontitis burden was observed among those aged 55-59 years, the incidence of periodontitis has shown an increasing trend among younger individuals. CONCLUSION: Periodontitis continues to be a global public health problem. Current prevention and control strategies should be enhanced to prevent an increase in periodontitis.

Sclerosing polycystic adenosis of the submandibular gland: Two case reports.

BACKGROUND: Sclerosing polycystic adenosis (SPA) is a rare disease of salivary glands, similar to fibrocystic disease of the breast. It occurs over a wide age range and exhibits a slight female preference. Most SPA cases have occurred in the parotid gland. The exact nature of SPA is unclear, but its tumor nature has recently been proposed. Although SPA has a good prognosis after adequate surgery, atypical lesions might occur, ranging from mild dysplasia to carcinoma in situ in some cases. To the best of our knowledge, only five cases of SPA in the submandibular gland have been reported to date. Here, we present two new cases of SPA involving the submandibular gland. CASE SUMMARY: A 50-year-old woman and a 52-year-old woman were referred to Tongji Hospital in Wuhan, China, with complaints of moderate pain, recurrent swelling, and a mass in the submandibular area. After admission, the two cases of the submandibular mass were examined physically. The boundary of the submandibular tumor was clear, and the range of motion was good. After preoperative examinations, surgery was performed on a selective basis. Postoperative histopathological examination revealed a well-defined mass with acinar structures, ducts, or cystic dilated glands of various sizes scattered in a large number of proliferative sclerosing stroma. There were flat and cuboidal cells, and eosinophils in the duct epithelium. There was also a eosinophilic substance in the lumen of dilated cysts. No atypical epithelial hyperplasia, invasive growth, or carcinoma in situ was found. Based on the above findings, the mass was diagnosed as SPA. Both patients have remained asymptomatic and no recurrence or distant metastasis had occurred by the 7-mo and 5-year follow-up, respectively. CONCLUSION: SPA is a rare disease of the salivary gland. Even though it has a good prognosis after adequate surgery, atypical lesions may occur from mild dysplasia to carcinoma in situ. However, no recurrence, distant metastasis, or mortality has been reported for submandibular gland SPA. Clinicians and pathologists should be familiar with the characteristics of SPA in the submandibular gland to avoid misdiagnosis and overtreatment.

Comprehensive profiling of protein lysine acetylation and its overlap with lysine succinylation in the Porphyromonas gingivalis fimbriated strain ATCC 33277.

Porphyromonas gingivalis is a pathogen closely associated with periodontal and systemic infections. Recently, lysine acetylation (Kac) and lysine succinylation (Ksuc) have been identified in bacterial proteins with diverse biological and pathological functions. The Ksuc of P. gingivalis ATCC 33277 has been characterized in our previous work, and here, we report the systematic analysis of Kac and its crosstalk with Ksuc in this bacterium. A combination of the affinity enrichment by the acetyl-lysine antibody with highly sensitive LC-MS/MS was used to identify the lysine-acetylated proteins and sites in P. gingivalis ATCC 33277. A total of 1,112 lysine-acetylated sites matching 438 proteins were identified. These proteins involved in several cellular processes, especially those proteins related to protein biosynthesis and central metabolism had a high tendency to be lysine acetylated. Moreover, lysine sites flanked by tyrosine, phenylalanine, and histidine in the +1 position, as well as residue lysine in position +4 to +5, were the targets of Kac. Additionally, proteins involved in adhesins, gingipains, black pigmentation, and oxidative stress resistance were identified as substrates of Kac. Collectively, these results suggest Kac may play a critical role in the regulation of physiology and virulence of P. gingivalis. Furthermore, we discovered that, Ksuc and Kac were extensively overlapped in P. gingivalis ATCC 33277, especially in proteins related to ribosomes and metabolism. This study provides a significant beginning for further investigating the role of Kac and Ksuc in the pathogenicity of P. gingivalis.

Global analysis of lysine succinylome in the periodontal pathogen Porphyromonas gingivalis.

The gram-negative anaerobe Porphyromonas gingivalis is not only a keystone periodontal pathogen but also an emerging systemic pathogen. Although the newly discovered protein post-translational modification (PTM), lysine succinylation (Ksuc), appears to play an important role in modulating metabolic processes in bacteria, this PTM has not been investigated in P gingivalis. In this study, we used a highly sensitive proteomics approach combining affinity enrichment with high-resolution liquid chromatography coupled with tandem mass spectrometry to examine Ksuc in P gingivalis. In total, 345 Ksuc sites in 233 proteins were identified and determined to be involved in a variety of cellular processes. In the region surrounding Ksuc sites, lysine residues were drastically overrepresented and sequence motifs with succinyl-lysine flanked by a lysine at the +3 or +6 positions appear to be unique to this pathogen. Additionally, our results suggest a crosstalk between Ksuc and glycosylation, but the overlap between Ksuc and acetylation in P gingivalis is quite different from that observed in other organisms. Notably, Ksuc was observed in proteins associated with established virulence factors, including gingipains, fimbriae, RagB, and PorR. Moreover, products of the factors necessary for P gingivalis in vitro survival (18.5%) were found to be succinylated at lysine sites and the same was observed in products of fitness factors for P gingivalis survival in both abscess and epithelial cell colonization environments (12%). Collectively, these results suggest that Ksuc may be a new mechanism in modulating the virulence, adaptation, and fitness of P gingivalis.

pckA-deficient Porphyromonas gingivalis W83 shows reduction in hemagglutination activity and alteration in the distribution of gingipain activity.

Bacterial metabolism during infection is related to bacterial persistence and virulence factors. Porphyromonas gingivalis is a key pathogen that contributes to chronic periodontitis. Our previous study showed that pckA, the gene encoding phosphoenolpyruvate carboxykinase, is a putative-specific pathogenic gene of virulent strains of P. gingivalis. Here, a pckA-deficient strain (ΔPG1676) was constructed in P. gingivalis W83. Virulence properties were compared between the mutant and wild-type strains. Specifically, hemagglutination activity was determined by the ability to agglutinate sheep erythrocytes. Gingipain activity was detected using synthetic-specific substrates. Gene expression levels were analyzed using RT-qPCR, and cell surface-associated polysaccharides were examined by silver staining and electron microscopy. Inactivation of the pckA gene did not affect bacterial growth and lipopolysaccharide formation but led to a reduction in hemagglutination activity and downregulation in expression of the hemagglutination-associated gene, rfa, when compared with the wild-type strain. Additionally, the ΔPG1676 mutant exhibited an alteration in the distribution of gingipain activity. Increased gingipain activity was detected on the cell surface, but a decrease in its activity in the culture supernatant was shown. Taken together, our results suggest that the pckA gene plays a role in modulating the virulence of P. gingivalis W83.

Maturation of the Mfa1 Fimbriae in the Oral Pathogen Porphyromonas gingivalis.

The Mfa1 fimbriae of the periodontal pathogen Porphyromonas gingivalis are involved in adhesion, including binding to synergistic species in oral biofilms. Mfa1 fimbriae are comprised of 5 proteins: the structural component Mfa1, the anchor Mfa2, and Mfa3-5 which constitute the fimbrial tip complex. Interactions among the Mfa proteins and the polymerization mechanism for Mfa1 are poorly understood. Here we show that Mfa3 can bind to Mfa1, 2, 4, and 5 in vitro, and may function as an adaptor protein interlinking other fimbrial subunits. Polymerization of Mfa1 is independent of Mfa3-5 and requires proteolytic processing mediated by the RgpA/B arginine gingipains of P. gingivalis. Both the N- and C- terminal regions of Mfa1 are necessary for polymerization; however, potential ß-strand disrupting amino acid substitutions in these regions do not impair Mfa1 polymerization. In contrast, substitution of hydrophobic amino acids with charged residues in either the N- or C- terminal domains yielded Mfa1 proteins that failed to polymerize. Collectively, these results indicate that Mfa3 serves as an adaptor protein between Mfa1 and other accessory fimbrial proteins. Mfa1 fimbrial polymerization is dependent on hydrophobicity in both the N- and C-terminal regions, indicative of an assembly mechanism involving the terminal regions forming a hydrophobic binding interface between Mfa1 subunits.

Poly[aqua-(µ(11)-4,6-dihy-droxy-benzene-1,3-disulfonato)-dipotassium].

In the title salt, [K(2)(C(6)H(4)O(8)S(2))(H(2)O)](n), both K(+) ions exhibit a seven-coordination with K-O bond lengths in the range 2.6600 (14) to 3.0522 (16) Å. One K(+) ion is coordinated by seven O atoms from the sulfonate and phenolic hy-droxy groups of six 4,6-dihy-droxy-benzene-1,3-disulfonate (L(2-)) anions while the other K(+) ion is coordinated by six O atoms from the sulfonate and phenolic hy-droxy groups of five L(2-) anions and one water O atom. The L(2-) anion exhibits chelating-bridging multidentate coordination to potassium, resulting in the formation of a cross-linked three-dimensional network.

1-(2-Bromo-2-de-oxy-ß-d-xylofuranos-yl)uracil.

In the title compound, C(9)H(11)BrN(2)O(5), the ribofuran-ose ring has a C2-exo, C3-endo twist configuration and is attached to the uracil unit via a ß-N(1)-glycosidic bond. The crystal structure is stabilized by two inter-molecular O-H⋯O inter-actions and one inter-molecular N-H⋯O inter-action.