Impact of Matrix Metalloproteinase-9 during Periodontitis and Cardiovascular Diseases

Matrix metalloproteinase-9 (MMP-9) has been shown to play a key role in endothelial function and perhaps pivotal in the correlation between periodontal disease and cardiovascular disease (CVD). For the study, the impact of MMP-9 of periodontitis and CVD on serum and saliva concentrations was analyzed. For the study patients with periodontitis (n = 31), CVD (n = 31), periodontitis + CVD (n = 31), and healthy patients (n = 31) were enrolled. Clinical and demographic characteristics as well as serum and salivary MMP-9 were evaluated. MMP-9 concentrations in serum and saliva were statistically elevated in patients with CVD (p < 0.01) and in patients with periodontitis plus CVD (p < 0.001) compared to patients with periodontitis and healthy subjects. Multivariate regression analysis showed that c-reactive protein (hs-CRP) was the only significant predictor for MMP-9 serum (p < 0.001), whereas hs-CRP (p < 0.001) and total cholesterol (p = 0.029) were the statistically significant salivary MMP-9 predictors. This study evidenced that patients with CVD and periodontitis + CVD presented elevated MMP-9 concentrations in serum and saliva compared to patients with periodontitis and healthy subjects. Furthermore, hs-CRP was a negative predictor of serum and salivary MMP-9.     

PLA Nanofibers for Microenvironmental-Responsive Quercetin Release in Local Periodontal Treatment

The management of periodontitis remains a vital clinical challenge due to the interplay between the microorganisms of the dental biofilm and the host inflammatory response leading to a degenerative process in the surrounding tissues. Quercetin (QUE), a natural flavonol found in many foods, including apples, onions and tea, has exhibited prolonged and strong antibiofilm and anti-inflammatory effects both in vitro and in vivo. However, its clinical application is limited by its poor stability and water solubility, as well as its low bioavailability. Thus, in the present study, electrospun polylactic acid (PLA) nanofibers loaded with different amounts (5–10% w/w) of QUE were produced to rapidly respond to the acidic microenvironment typical of periodontal pockets during periodontal disease. This strategy demonstrated that PLA-QUE membranes can act as a drug reservoir releasing high QUE concentrations in the presence of oral bacterial infection (pH < 5.5), and thus limiting Pseudomonas aeruginosa PAO1 and Streptococcus mutans biofilm maturation. In addition, released QUE exerts antioxidant and anti-inflammatory effects on P. gingivalis Lipopolysaccharide (LPS)-stimulated human gingival fibroblast (HGFs). The reported results confirmed that PLA-QUE membranes could inhibit subgingival biofilm maturation while reducing interleukin release, thereby limiting host inflammatory response. Overall, this study provided an effective pH-sensitive drug delivery system as a promising strategy for treating periodontitis.     

Thermosensitive acetylated carboxymethyl chitosan gel depot systems sustained release caffeic acid phenethyl ester for periodontitis treatment

Periodontitis is a chronic inflammatory disease of tooth support tissues leading to progressive destruction of periodontal soft tissues as well as alveolar bone, and can be treated with anti-inflammatory and bone-protective agents to prevent disease progression. Caffeic acid phenethyl ester (CAPE) is a natural polyphenolic compound with anti-inflammation, anti-oxidation and bone tissue repair efficacy. In this work, we synthesized a thermosensitive hydrogel matrix of acetylated carboxymethyl chitosan (A-CC), and firstly applied for periodontal local drug delivery. The biocompatible CAPE-loaded A-CC hydrogel (CAPE-A-CC) has the advantages of forming a drug depot in situ, sustained release and precisely improving the drug concentration in the lesion sites compared with traditional systemic administration. In addition, CAPE-A-CC could significantly inhibit the expression of inflammatory cytokines of TNF-α, IL-1β, IL-6, and IL-17 in macrophages, and increased the expression of alkaline phosphatase (ALP) in human periodontal ligament stem cells (hPDLSC) related to osteogenesis. This study develops a novel in situ thermosensitive hydrogel delivery system to improve the therapeutic potential of natural active ingredient for periodontitis therapy.     

Recent Development of Active Ingredients in Mouthwashes and Toothpastes for Periodontal Diseases

Periodontal diseases like gingivitis and periodontitis are primarily caused by dental plaque. Several antiplaque and anti-microbial agents have been successfully incorporated into toothpastes and mouthwashes to control plaque biofilms and to prevent and treat gingivitis and periodontitis. The aim of this article was to review recent developments in the antiplaque, anti-gingivitis, and anti-periodontitis properties of some common compounds in toothpastes and mouthwashes by evaluating basic and clinical studies, especially the ones published in the past five years. The common active ingredients in toothpastes and mouthwashes included in this review are chlorhexidine, cetylpyridinium chloride, sodium fluoride, stannous fluoride, stannous chloride, zinc oxide, zinc chloride, and two herbs—licorice and curcumin. We believe this comprehensive review will provide useful up-to-date information for dental care professionals and the general public regarding the major oral care products on the market that are in daily use.     

Synchrotron radiation analysis of possible correlations between metal status in human cementum and periodontal disease

Periodontitis is a serious disease that affects up to 50% of an adult population. It is a chronic condition involving inflammation of the periodontal ligament and associated tissues leading to eventual tooth loss. Some evidence suggests that trace metals, especially zinc and copper, may be involved in the onset and severity of periodontitis. Thus we have used synchrotron X‐ray fluorescence imaging on cross sections of diseased and healthy teeth using a microbeam to explore the distribution of trace metals in cementum and adhering plaque. The comparison between diseased and healthy teeth indicates that there are elevated levels of zinc, copper and nickel in diseased teeth as opposed to healthy teeth. This preliminary correlation between elevated levels of trace metals in the cementum and plaque of diseased teeth suggests that metals may play a role in the progress of periodontitis.     

Simultaneous Quantitative Analysis of Ginsenosides Isolated from the Fruit of Panax ginseng C.A. Meyer and Regulation of HO-1 Expression through EGFR Signaling Has Anti-Inflammatory and Osteogenic Induction Effects in HPDL Cells

Periodontitis is a set of chronic inflammatory diseases caused by the accumulation of Gram-negative bacteria on teeth, resulting in gingivitis, pocket formation, alveolar bone loss, tissue destruction, and tooth loss. In this study, the contents of ginsenosides isolated from Panax ginseng fruit extract were quantitatively analyzed, and the anti-inflammatory effects were evaluated in human periodontal ligament cells. The major ginsenosides, Re, Ra8, and Rf, present in ginseng fruit were simultaneously analyzed by a validated method using high-performance liquid chromatography with a diode-array detector; Re, Ra8, and Rf content per 1 g of P. ginseng fruit extract was 1.01 ± 0.03, 0.33 ± 0.01, and 0.55 ± 0.04 mg, respectively. Ginsenosides-Re, -Ra8, and -Rf inhibited the production of pro-inflammatory factors and the expression of important cytokines in periodontitis by inducing the expression of heme oxygenase 1 (HO-1), promoting osteoblast differentiation of periodontal ligament cells, suppressing alveolar bone loss, and promoting the expression of osteoblast-specific genes, such as alp, opn, and runx2. An inhibitory effect of these ginsenosides on periodontitis and alveolar bone loss was observed via the regulation of HO-1 and subsequent epidermal growth factor receptor (EGFR) signaling. Silencing EGFR with EGFR siRNA confirmed that the effect of ginsenosides on HO-1 is mediated by EGFR. In conclusion, this study evaluated the contents of ginsenosides-Re, -Ra8, and -Rf isolated from P. ginseng fruit extract. Therefore, these results provide important basic data for future P. ginseng fruit component studies and suggest that ginsenosides Re, Ra8, and Rf have potential as future treatment options for periodontitis.     

Local Oral Delivery Agents with Anti-Biofilm Properties for the Treatment of Periodontitis and Peri-Implantitis. A Narrative Review

Despite many discoveries over the past 20 years regarding the etiopathogenesis of periodontal and peri-implant diseases, as well as significant advances in our understanding of microbial biofilms, the incidence of these pathologies continues to rise. For this reason, it was clear that other strategies were needed to eliminate biofilms. In this review, the literature database was searched for studies on locally delivered synthetic agents that exhibit anti-biofilm properties and their potential use in the treatment of two important oral diseases: periodontitis and peri-implantitis.     

基于CBCT研究伴牙周炎患者种植牙治疗同期行GBR技术对牙槽骨的影响

本文探讨伴牙周炎患者种植牙同期行引导性骨再生(GBR)技术治疗对牙槽骨吸收的影响。选取接受牙种植同期行GBR技术治疗的患者90例作为研究对象,其中伴有牙周炎的患者有42例(牙周炎组)、不伴有牙周炎的患者有48例(对照组),采用CBCT观察两组的牙槽骨参数并进行比较。负载2年后(T2),牙周炎组患者的牙槽骨近中点、远中点、舌侧的牙槽骨高度测定值[(2.64±0.09)mm、(2.66±0.13)mm、(3.91±0.16)mm]均低于对照组的[(2.76±0.13)mm、(2.72±0.11)mm、(3.99±0.18)mm],且差异具有统计学意义(P<0.05);牙周炎组患者的牙槽嵴顶区舌侧、牙槽嵴顶区唇侧、根尖区舌侧的牙槽骨密度值[(1054.1±97.6)Hu、(1058.3±113.0)Hu、(989.1±98.0)Hu]均低于对照组的[(1147.3±133.0)Hu、(1103.0±86.3)Hu、(1067.6±103.8)Hu],且差异具有统计学意义(P<0.05)。与无牙周炎病史的患者相比,具有牙周炎病史的牙缺损患者接受牙种植同期行GBR技术治疗后种植体周围骨吸收更加的明显,CBCT技术能较好地观察到种植体周围骨吸收的情况。     

Cold Atmospheric Plasma Jet as a Possible Adjuvant Therapy for Periodontal Disease

Due to the limitations of traditional periodontal therapies, and reported cold atmospheric plasma anti-inflammatory/antimicrobial activities, plasma could be an adjuvant therapy to periodontitis. Porphyromonas gingivalis was grown in blood agar. Standardized suspensions were plated on blood agar and plasma-treated for planktonic growth. For biofilm, dual-species Streptococcus gordonii + P. gingivalis biofilm grew for 48 h and then was plasma-treated. XTT assay and CFU counting were performed. Cytotoxicity was accessed immediately or after 24 h. Plasma was applied for 1, 3, 5 or 7 min. In vivo: Thirty C57BI/6 mice were subject to experimental periodontitis for 11 days. Immediately after ligature removal, animals were plasma-treated for 5 min once—Group P1 (n = 10); twice (Day 11 and 13)—Group P2 (n = 10); or not treated—Group S (n = 10). Mice were euthanized on day 15. Histological and microtomography analyses were performed. Significance level was 5%. Halo diameter increased proportionally to time of exposure contrary to CFU/mL counting. Mean/SD of fibroblasts viability did not vary among the groups. Plasma was able to inhibit P. gingivalis in planktonic culture and biofilm in a cell-safe manner. Moreover, plasma treatment in vivo, for 5 min, tends to improve periodontal tissue recovery, proportionally to the number of plasma applications.     

Gene Interaction Network Analysis Reveals IFI44L as a Drug Target in Rheumatoid Arthritis and Periodontitis

Simple SummaryIn spite of substantial investigation, the biological link between periodontitis and rheumatoid arthritis remains unexplained. This study intended to correlate periodontitis and rheumatoid arthritis gene expression patterns to find shared targets for both the disease. We identified the differentially expressed genes (DEGs) in periodontitis and rheumatoid arthritis. The network was built by integrating DEGs and ranking the genes using GeneMANIA. FINDSITEcomb2.0 was used to find a possible inhibitor for the top-ranked gene. Further, the binding effectiveness and protein-ligand complex stability were then determined by molecular docking and molecular dynamics. The network analysis showed IFI44L as a highly ranking gene implicated in most immunological pathways. A virtual screening of 6507 compounds revealed vemurafenib as the best candidate for the IFI44L target. Molecular docking and molecular dynamics modelling revealed the stability of the IFI44L-vemurafenib complex, which suggest IFI44L is potential target and vemurafenib could be the better candidate to treat both diseases.AbstractObjective: Despite extensive research on periodontitis and rheumatoid arthritis, the underlying molecular connectivity between these condition remains largely unknown. This research aimed to integrate periodontitis and rheumatoid arthritis gene expression profiles to identify interconnecting genes and focus to develop a common lead molecule against these inflammatory conditions. Materials and Methods: Differentially expressed genes (DEGs) of periodontitis and rheumatoid arthritis were identified from the datasets retrieved from the Gene Expression Omnibus database. The network was constructed by merging DEGs, and the interconnecting genes were identified and ranked using GeneMANIA. For the selected top ranked gene, the potential inhibitor was searched using FINDSITE^comb2.0. Subsequently, the molecular docking and molecular dynamics were performed to determine the binding efficiency and protein-ligand complex stability, respectively. Results: From the network analysis, IFN-induced protein 44-like (IFI44L) was identified as a top ranked gene involved in most of the immunological pathway. With further virtual screening of 6507 molecules, vemurafenib was identified to be the best fit against the IFI44L target. The binding energy and stability of IFI44L with vemurafenib were investigated using molecular docking and molecular dynamics simulation. Docking results show binding energy of −7.7 Kcal/mol, and the simulation results show stability till 100 ns. Conclusions: The identified IFI44L may represent a common drug target for periodontitis and rheumatoid arthritis. Vemurafenib could be a potent anti-inflammatory drug for both diseases.