Abstract
To evaluate the prognostic accuracy of microbial biomarkers and their associations with the response to active periodontal treatment (APT) and supportive periodontal therapy (SPT). Microbial ...dysbiosis plays a crucial role in the disease processes of periodontitis. Biomarkers based on microbial composition may offer additional prognostic value, supplementing the limitations of current clinical parameters. While these microbial biomarkers have been clinically evaluated, there is a lack of consensus regarding their prognostic accuracy. A structured search strategy was applied to MEDLINE (PubMed), Cochrane Library, and Embase on 1/11/2022 to identify relevant publications. Prospective clinical studies involving either APT or SPT, with at least 3‐month follow‐up were included. There were no restrictions on the type of microbial compositional analysis. 1918 unique records were retrieved, and 13 studies (comprising 943 adult patients) were included. Heterogeneity of the studies precluded a meta‐analysis, and none of the included studies had performed the sequence analysis of the periodontal microbiome. Seven and six studies reported on response to APT and SPT, respectively. The prognostic accuracy of the microbial biomarkers for APT and SPT was examined in only two and four studies, respectively. Microbial biomarkers had limited predictive accuracy for APT and inconsistent associations for different species across studies. For SPT, elevated abundance of periodontal pathogens at the start of SPT was predictive of subsequent periodontal progression. Similarly, persistent high pathogen loads were consistently associated with progressive periodontitis, defined as an increased pocket probing depth or clinical attachment loss. While there was insufficient evidence to support the clinical use of microbial biomarkers as prognostic tools for active periodontal treatment outcomes, biomarkers that quantify periodontal pathogen loads may offer prognostic value for predicting progressive periodontitis in the subsequent supportive periodontal therapy phase. Additional research will be required to translate information regarding subgingival biofilm composition and phenotype into clinically relevant prognostic tools.
To evaluate the mechanical and antimicrobial properties of boron-containing coating on translucent zirconia (5Y-PSZ).
5Y-PSZ discs (Control) were coated with a glaze (Glaze), silver- (AgCoat), or ...boron-containing (BCoat) glasses. The coatings' antimicrobial potential was characterized using S. mutans biofilms after 48 h via viable colony-forming units (CFU), metabolic activity (CV) assays, and quantification of extracellular polysaccharide matrix (EPS). Biofilm architectures were imaged under scanning electron and confocal laser scanning microscopies (SEM and CLSM). The cytocompatibility was determined at 24 h via WST-1 and LIVE&DEAD assays using periodontal ligament stem cells (PDLSCs). The coatings' effects on properties were characterized by Vickers hardness, biaxial bending tests, and fractography analysis. Statistical analyses were performed via one-way ANOVA, Tukey's tests, Weibull analysis, and Pearson's correlation analysis.
BCoat significantly decreased biofilm formation, having the lowest CFU and metabolic activity compared with the other groups. BCoat and AgCoat presented the lowest EPS, followed by Glaze and Control. SEM and CLSM images revealed that the biofilms on BCoat were thin and sparse, with lower biovolume. In contrast, the other groups yielded robust biofilms with higher biovolume. The cytocompatibility was similar in all groups. BCoat, AgCoat, and Glaze also presented similar hardness and were significantly lower than Control. BCoat had the highest flexural strength, characteristic strength and Weibull parameters (σ
: 625 MPa; σ
: 620 MPa; m = 11.5), followed by AgCoat (σ
: 464 MPa; σ
: 478 MPa; m = 5.3).
BCoat is a cytocompatible coating with promising antimicrobial properties that can improve the mechanical properties and reliability of 5Y-PSZ.
Resveratrol (RES) is a natural polyphenol with potential as an adjunctive therapeutic modality for periodontitis. However, its inferior pharmacokinetics and toxicity concerns about its commonly used ...solvent dimethyl sulfoxide (DMSO) hinder translation to clinical applicability. Our study aimed to investigate the comparative antimicrobial properties of RES and its analogues (pterostilbene PTS, oxyresveratrol OXY and piceatannol PIC), utilizing 2-hydroxypropyl-β-cyclodextrin (HPβCD) as a solubiliser, which has a well-documented safety profile and FDA approval. These properties were investigated against Fusobacterium nucleatum, a key periodontal pathogen. PTS demonstrated the most potent antibacterial effects in HPβCD, with MIC > 60-fold lower than that of RES, OXY and PIC. In addition, PTS inhibited F. nucleatum biofilm formation. PTS exerted antimicrobial effects by eliciting leakage of cellular contents, leading to loss of bacterial cell viability. PTS also conferred immunomodulatory effects on F. nucleatum-challenged macrophages via upregulation of antioxidant pathways and inhibition of NF-κB activation. Given the superior antimicrobial potency of PTS against F. nucleatum compared to RES and other analogues, and coupled with its immunomodulatory properties, PTS complexed with HPβCD holds promise as a candidate nutraceutical for the adjunctive treatment of periodontitis.
The cytolethal distending toxin (Cdt) of Actinobacillus actinomycetemcomitans, a periodontal pathogen, is a newly described cytotoxin with immunosuppressive properties, capable of causing cell cycle ...arrest of lymphocytes. The objectives of this study were to investigate the occurrence of A. actinomycetemcomitans with the cdt genotype in the subgingival plaque of periodontitis patients and to determine the association of this bacterial genotype with periodontal disease. A total of 146 subgingival plaque samples from periodontitis patients were assayed by the PCR method using oligonucleotide primers targeting the cdt operon of A. actinomycetemcomitans. Primers targeting the leukotoxin gene A (ltxA) of A. actinomycetemcomitans was used to determine the occurrence of the bacteria in the plaque samples at baseline. At baseline, A. actinomycetemcomitans was detected in 106 out of 146 (73%) diseased sites studied. Among the 106 diseased sites found to harbor A. actinomycetemcomitans, 13 sites were positive for the bacteria with the cdt genotype (12%). Out of the 13 positive sites, 10 sites were obtained from patients diagnosed with aggressive periodontitis (77%). Thus, A. actinomycetemcomitans with the cdt genetic subtype has low occurrence in the subgingival plaque of periodontitis patients. However, a strong association was observed between the presence of the bacteria and aggressive forms of periodontitis. Thus, the cytotoxic and immunosuppressive properties of A. actinomycetemcomitans Cdt may function to cripple the host immunity and contribute to the pathogenesis of aggressive periodontitis.
Scope
To evaluate the health‐promoting potentials of piceatannol (PIC), a dietary resveratrol derivative, its biotransformation is examined.
Methods and results
The biotransformation is tested in ...human/rat hepatic microsomes and cytosols; its pharmacokinetic profiles are assessed in rats. Although limited phase I metabolism exists in microsomes, PIC is rapidly converted to two pharmacologically active metabolites, namely rhapontigenin (RHA) and isorhapontigenin (ISO) in cytosols. Such biotransformation is completely blocked by entacapone, a well‐known catechol‐O‐methyltransferase (COMT) inhibitor, demonstrating that the O‐methylation is mediated by COMT. Moreover, PIC is identified as a substrate inhibitor of COMT, suggesting its potential benefits in Alzheimer's disease. Due to extensive phase II metabolism including glucuronidation, sulfation, and O‐methylation, PIC displays rapid clearance and at least 4.02% ± 0.61% and 17.70% ± 0.91% of PIC is converted to RHA and ISO, respectively, in rats after intravenous administration. Similarly, PIC serves as an effective precursor of ISO upon oral administration.
Conclusion
Since PIC and its metabolites possess pleiotropic health‐promoting activities, it has emerged as a promising nutraceutical candidate for further development. This study also reinforces the importance of in vivo testing in nutritional researches as the active metabolite(s) may be absent from the in vitro system.
Piceatannol is substantially O‐methylated to rhapontigenin and isorhapontigenin by catechol‐O‐methyltransferase (COMT). As a COMT substrate inhibitor, piceatannol displays health potential for Alzheimer's disease. Piceatannol, rhapontigenin, and isorhapontigenin are extensively metabolized by glucuronosyltransferase (UGT) and/or sulfotransferase (SULT), which can be reversed by glucuronidase (GLU) and sulfatase (STS). Clearly, active metabolites and reversed metabolism contribute to the health‐promoting effects of piceatannol.
The ability of human embryonic stem cells (hESCs) to proliferate indefinitely is attributed to its high telomerase activity and associated long telomere. However, factors regulating telomere length ...in hESCs remain largely uncharacterized. The aims of this study were, to identify factors which modulate telomere length of hESCs, and to determine if the telomere length of hESCs influences cellular senescence of its differentiated progeny cells. Telomerase reverse transcriptase (TERT) gene expression, telomerase activity and telomere length of hESCs cultured in different culture systems were compared. Genetically identical hESCs of different telomere lengths were differentiated into fibroblasts simultaneously, and the population doubling and cellular senescence levels were determined. We found that telomere lengths were significantly different in different culture systems and Fibroblast growth factor-2 (FGF-2) upregulated TERT expression, telomerase activity and telomere length via Wnt/β-catenin signaling pathway in hESCs in a significant manner. We also provide evidence that fibroblast differentiated from hESCs with longer telomere exhibited significant more population doublings and longer life span than those derived from hESCs with shorter telomeres. Thus, FGF-2 levels in hESCs culture systems can be manipulated to generate cells with longer telomere which would be advantageous in the applications of hESCs in regenerative medicine.
Objectives
This study aims to investigate longitudinally the activation of Toll-like receptor-4 (TLR-4) by subgingival biofilm samples before and after nonsurgical periodontal therapy (NSPT).
...Materials and methods
Forty periodontitis patients received NSPT and were reviewed 3 and 6 months post-treatment. Subgingival biofilm was sampled from 4 teeth per patient, at baseline and each follow-up time point. TLR-4 activation was determined using the HEK-BLUE™/hTLR4 system. Changes in TLR-4 activation and probing pocket depths (PPDs) were evaluated using generalised linear models, and the association between TLR-4 activation and pocket reduction (defined as 6-month PPDs ≤ 3mm) was determined using generalised estimating equations.
Results
At 6 months, the mean TLR-4 activation by subgingival biofilm samples was significantly reduced from 11.2AU (95%CI 7.1AU, 15.4AU) to 3.6AU (95%CI 2.3AU, 4.8AU,
p
< 0.001), paralleling significant reductions in mean PPDs at sampled sites. The response to NSPT was associated with longitudinal TLR-4 activation profiles, with significantly higher TLR-4 activation by subgingival biofilm obtained from sites that did not achieve pocket reduction, compared to sites at which pocket reduction was achieved.
Conclusions
The activation of TLR-4 by subgingival biofilm samples was reduced after NSPT, and this reduction was significantly associated with the clinical improvements (PPD reductions) at sampled sites.
Clinical relevance
This study demonstrated an association between the longitudinal profile of TLR-4 activation by subgingival biofilm and periodontal treatment response. Longitudinal monitoring of TLR-4 activation by subgingival biofilm may potentially identify non-responsive sites, enabling targeted additional treatment.
Mol. Nutr. Food Res. 2020, 64, 1900905
DOI: 10.1002/mnfr.201900905
In article number 1900905, Hai‐Shu Lin and co‐workers find that piceatannol is extensively converted to two pharmacologically active ...metabolites, rhapontigenin and isorhapontigenin, by catechol‐O‐methyltransferase. Moreover, piceatannol is identified as a substrate inhibitor of catechol‐O‐methyltransferase. This study also suggests that active metabolites and reversed metabolism of piceatannol contribute to its health‐promoting effects.
Periodontitis is a common chronic inflammatory disease driven by the interaction between a dysbiotic oral microbiome and the dysregulated host immune-inflammatory response. Naturally derived ...nutraceuticals, such as resveratrol and its analogs, are potential adjunctive therapies in periodontal treatment due to their antimicrobial and anti-inflammatory properties. Furthermore, different analogs of resveratrol and the choice of solvents used may lead to varying effects on therapeutic properties. This review presents the current findings and gaps in our understanding on the potential utility of resveratrol and its analogs in periodontal treatment.
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