In the initiation or exacerbation of Alzheimer disease, the dissemination of oral microorganisms into the brain tissue or the low‐level systemic inflammation have been speculated to play a role. ...However, the impact of oral microorganisms, such as Porphyromonas gingivalis, on the pathogenesis of Alzheimer disease and the potential causative relationship is still unclear. The present review has critically reviewed the literature by examining the following aspects: (a) the oral microbiome and the immune response in the elderly population, (b) human studies on the association between periodontal and gut microorganisms and Alzheimer disease, (c) animal and in vitro studies on microorganisms and Alzheimer disease, and (d) preventive and therapeutic approaches. Factors contributing to microbial dysbiosis seem to be aging, local inflammation, systemic diseases, wearing of dentures, living in nursing homes and no access to adequate oral hygiene measures. Porphyromonas gingivalis was detectable in post‐mortem brain samples. Microbiome analyses of saliva samples or oral biofilms showed a decreased microbial diversity and a different composition in Alzheimer disease compared to cognitively healthy subjects. Many in‐vitro and animal studies underline the potential of P gingivalis to induce Alzheimer disease‐related alterations. In animal models, recurring applications of P gingivalis or its components increased pro‐inflammatory mediators and β‐amyloid in the brain and deteriorated the animals' cognitive performance. Since periodontitis is the result of a disturbed microbial homoeostasis, an effect of periodontal therapy on the oral microbiome and host response related to cognitive parameters may be suggested and should be elucidated in further clinical trials.
Introduction Recent studies have demonstrated a positive role of hyaluronic acid (HA) on periodontal clinical outcomes. This in-vitro study aimed to investigate the impact of four different HAs on ...interactions between periodontal biofilm and immune cells. Methods The four HAs included: high-molecular-weight HA (HHA, non-cross-linked), low-molecular-weight HA (LHA), oligomers HA (OHA), and cross-linked high-molecular-weight HA (CHA). Serial experiments were conducted to verify the influence of HAs on: (i) 12-species periodontal biofilm (formation and pre-existing); (ii) expression of inflammatory cytokines and HA receptors in monocytic (MONO-MAC-6) cells and periodontal ligament fibroblasts (PDLF) with or without exposure to periodontal biofilms; (iii) generation of reactive oxygen species (ROS) in MONO-MAC-6 cells and PDLF with presence of biofilm and HA. Results The results indicated that HHA and CHA reduced the bacterial counts in a newly formed (4-h) biofilm and in a pre-existing five-day-old biofilm. Without biofilm challenge, OHA triggered inflammatory reaction by increasing IL-1β and IL-10 levels in MONO-MAC cells and IL-8 in PDLF in a time-dependent manner, whereas CHA suppressed this response by inhibiting the expression of IL-10 in MONO-MAC cells and IL-8 in PDLF. Under biofilm challenge, HA decreased the expression of IL-1β (most decreasing HHA) and increased IL-10 levels in MONO-MAC-6 cells in a molecular weight dependent manner (most increasing CHA). The interaction between HA and both cells may occur via ICAM-1 receptor. Biofilm stimulus increased ROS levels in MONO-MAC-6 cells and PDLF, but only HHA slightly suppressed the high generation of ROS induced by biofilm stimulation in both cells. Conclusion Overall, these results indicate that OHA induces inflammation, while HHA and CHA exhibit anti-biofilm, primarily anti-inflammatory, and antioxidant properties in the periodontal environment.
Periodontitis is an inflammatory condition initiated by oral bacteria and is associated with several systemic diseases. Quercetin is an anti-inflammatory and anti-bacterial poly-phenol present in ...various foods. The aim of this meta-analysis was the evaluation of the effects of quercetin administration in animal models of experimental periodontitis.
A systematic search was performed in electronic databases using the following search terms: "periodontitis" or "periodontal disease" or "gingivitis" and "quercetin" or "cyanidanol" or "sophoretin" or "pentahydroxyflavone". In vivo preclinical animal models of experimental periodontal disease with a measurement of alveolar bone loss were included in the analysis. The risk of bias of the included studies was assessed using the SYRCLE tool.
The systematic search yielded 335 results. Five studies were included, four of them qualified for a meta-analysis. The meta-analysis showed that quercetin administration decreased alveolar bone loss (τ
= 0.31, 1.88 mm 95%CI: 1.09, 2.67) in experimental periodontal disease animal models. However, the risk of bias assessment indicated that four SYRCLE domains had a high risk of bias.
Quercetin diminishes periodontal bone loss and prevents disease progression in animal models of experimental periodontal disease. Quercetin might facilitate periodontal tissue hemostasis by reducing senescent cells, decreasing oxidative stress via SIRT1-induced autophagy, limiting inflammation, and fostering an oral bacterial microenvironment of symbiotic microbiota associated with oral health. Future research will show whether and how the promising preclinical results can be translated into the clinical treatment of periodontal disease.
Propolis is increasingly being discussed as an alternative to commonly used antiseptics. This in vitro study focused on the ethanolic extract of green Brazilian propolis (EEPg) as an additive in an ...oral health care product. We investigated (i) a potential inflammation-modulation activity of EEPg when a periodontal or Candida biofilm was exposed to monocytic (MONO-MAC-6) cells, (ii) the adhesion of oral pathogens to gingival keratinocytes and (iii) the antimicrobial and antibiofilm effect of different toothpaste formulations. EEPg decreased the levels of interleukin (IL)-1β and increased IL-10 in MONO-MAC cells challenged with a periodontal biofilm. In contact with TIGK cells, EEPg reduced the numbers of adherent
to 0.5% but did not affect the adhesion of
. The frequent brushing of a cariogenic biofilm with a toothpaste supplemented with EEPg reduced the surface microhardness loss of enamel specimens. Mixing an experimental erythritol toothpaste with 25 and 50 mg/mL of EEPg confirmed the antibacterial activity of EEPg against oral bacteria and particularly inhibited periodontal biofilm formation. The suggested toothpaste formulations seem to have potential in the prevention of caries, gingivitis and periodontitis and should be evaluated in further in vitro research and in clinical trials.
•The phenomenon of CPE is experimentally verified for a non-linear chemical reaction.•The transient extremum can be an approximate momentary partial equilibrium.•Kinetic parameters can be determined ...based on the “reactant-product’’ intersection.
The phenomenon of ‘‘conservatively perturbed equilibrium’’ (CPE) for a complex non-linear chemical system was experimentally verified in a batch reactor in which ethanol and benzyl alcohol react with acetic acid producing two different esters and water. Three possible CPE cases, i.e., acetic acid and water unperturbed, ethanol and ethyl acetate unperturbed, benzyl alcohol and benzyl acetate unperturbed, were systematically investigated. For unperturbed substances with initial concentrations of their corresponding equilibrium concentrations, unavoidable extreme values were observed in relaxation to the equilibrium. If the unperturbed substances were involved in two reactions, a proper momentary partial equilibrium was not observed at the transient extremum. However, the transient extremum could be an approximate momentary partial equilibrium for the reaction of the unperturbed substance if the rate of some step is insignificant. This fact provides essential information about the detailed mechanism of the complex reaction.
H2S reforming of methane (HRM) provides a potential strategy to directly utilize sour natural gas for the production of CO x -free H2 and sulfur chemicals. Several carbon allotropes were found to be ...active and selective for HRM, while the additional presence of transition metals led to further rate enhancements and outstanding stability (e.g., Ru supported on carbon black). Most metals are transformed to sulfides, but the carbon supports prevent sintering under the harsh reaction conditions. Supported by theoretical calculations, kinetic and isotopic investigations with representative catalysts showed that H2S decomposition and the recombination of surface H atoms are quasi-equilibrated, while the first C–H bond scission is the kinetically relevant step. Theory and experiments jointly establish that dynamically formed surface sulfur dimers are responsible for methane activation and catalytic turnovers on sulfide and carbon surfaces that are otherwise inert without reaction-derived active sites.
H
S reforming of methane (HRM) provides a potential strategy to directly utilize sour natural gas for the production of CO
-free H
and sulfur chemicals. Several carbon allotropes were found to be ...active and selective for HRM, while the additional presence of transition metals led to further rate enhancements and outstanding stability (e.g., Ru supported on carbon black). Most metals are transformed to sulfides, but the carbon supports prevent sintering under the harsh reaction conditions. Supported by theoretical calculations, kinetic and isotopic investigations with representative catalysts showed that H
S decomposition and the recombination of surface H atoms are quasi-equilibrated, while the first C-H bond scission is the kinetically relevant step. Theory and experiments jointly establish that dynamically formed surface sulfur dimers are responsible for methane activation and catalytic turnovers on sulfide and carbon surfaces that are otherwise inert without reaction-derived active sites.
This study aimed to establish a framework for the role of discoidin domain receptor 1 (DDR1) in oral squamous cell carcinoma (OSCC) through biological data and functional analysis.
The GSE31056 ...series of the Gene Expression Omnibus database and UALCAN website were used to assess DDR1 expression in head and neck squamous cell carcinoma (HNSCC) and OSCC. DDR1 RNA sequencing data for 260 HNSCC samples from The Cancer Genome Atlas were overlaid to evaluate its association with tumor progression and prognosis. To identify the function of DDR1 in OSCC, 38 patients with OSCC were followed for 8 years and immunohistochemical analysis, western blotting, Cell Counting Kit-8, and colony formation assays were conducted on OSCC cell lines to reveal DDR1 expression and function.
DDR1 was overexpressed in HNSCC and OSCC tumor specimens and its expression correlated with overall survival and T-stage classification (P = .049, P = .0316). Furthermore, DDR1 was related to OSCC tumor growth because its expression increased with the T-stage level (P = .0071) but not N-stage level, histologic stage, or recurrence (P > .05). DDR1 was highly expressed in OSCC cell lines and promoted cell proliferation, which was repressed by nilotinib (P < .05).
DDR1 has an oncogenic role in OSCC and might be a novel target for anti-OSCC therapy.
Objectives
A beneficial effect of cross-linked hyaluronic acid (cHA) on periodontal wound healing and regeneration has recently been demonstrated. The present in vitro study was designed to obtain ...deeper knowledge on the effect of cHA when applied in the gingival sulcus (serum-rich environment) during non-surgical periodontal therapy.
Materials and methods
The influence of cHA, human serum (HS), and cHA/HS on (i) a 12-species biofilm formation, (ii) the adhesion of periodontal ligament fibroblasts (PDLF) to dentine surface, (iii) the expression and secretion of interleukin-8, and (iv) the expression of receptors of HA in PDLF and gingival fibroblasts (GF) were evaluated.
Results
At 4 h of biofilm formation, cHA and HS in combination (cHA/HS) slightly decreased the colony-forming unit counts in biofilm whereas the metabolic activity of biofilm was reduced in all test groups (cHA, HS, cHA/HS) vs. control. At 24 h, the quantity of biofilm was reduced in all test groups vs. untreated control. The test substances did not affect adhesion of PDLF to dentin. HS increased the expression of IL-8 by PDLF and GF which was partially downregulated by cHA. HS and/or cHA promoted the expression of the HA receptor RHAMM in GF but not in PDLF.
Conclusions
In summary, the present data indicate that serum neither negatively affect the activity of cHA against periodontal biofilm nor had any unwanted influence on the activity of PDLF.
Clinical relevance
These findings lend additional support for the positive effects of cHA on cells involved in periodontal wound healing, thus pointing to its potential use in non-surgical periodontal therapy.
Background
Oral submucous fibrosis (OSF) is a potentially malignant lesion characterized by epithelial‐mesenchymal transition (EMT). Bone morphogenetic protein 4 (BMP4) promotes EMT in fibrotic ...diseases, but the underlying mechanisms and its potential role in OSF are unclear. This study investigates whether BMP4 plays a role in the pathogenesis of OSF and explores the underlying mechanisms.
Methods
The expression of BMP4 and the EMT proteins E‐cadherin and vimentin was investigated in OSF specimens by immunohistochemical staining. Pearson's correlation analysis was conducted to explore the correlation between BMP4 and the EMT markers. Western blotting and RT‐PCR assays were used to analyze the effect of arecoline (a known EMT‐promoting pathogenic factor in OSF) on BMP4 and identify the transcription factor involved. Confocal microscopy was used to observe the intracellular sublocalization of the identified transcription factor, Yes‐associated protein 1 (YAP1). Finally, siRNA silencing of BMP4 was used to determine its effect on YAP1 activation and arecoline‐induced EMT.
Results
BMP4 is overexpressed in OSF and plays a role in EMT, as its expression correlates with the expression of E‐cadherin and vimentin. Arecoline induces BMP4 expression via the activation of YAP1 (through its nuclear translocation). Furthermore, the YAP1/BMP4 mechanism is the main molecular event in arecoline‐induced EMT, as knockdown of BMP4 expression affects expression of the EMT markers and inhibits extracellular matrix accumulation.
Conclusions
Arecoline induces EMT in OSF via the YAP1/BMP4 pathway. Thus, BMP4 could be considered as a potential therapeutic target for the treatment of OSF.
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