Oxidative Stress and FOXO-1 Relationship in Stage III Periodontitis.

OBJECTIVES: 8-Hydroxideoxyguanosine (8-OHdG) is a marker of oxidative stress, and Forkhead Box-O1 (FOXO1) is a transcription factor and signaling integrator in cell and tissue homeostasis. This study aims to determine FOXO1 and 8-OHdG levels in serum and saliva samples of periodontitis patients and to evaluate their relationship with clinical periodontal parameters. MATERIALS AND METHODS: Twenty healthy individuals, twenty generalized Stage III Grade B periodontitis patients, and nineteen generalized Stage III Grade C periodontitis patients were included in the study. Clinical periodontal parameters (plaque index (PI), probing depth (PD), bleeding on probing (BOP), and clinical attachment level (CAL)) were recorded. Salivary and serum 8-OHdG and FOX-O1 levels were analyzed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Clinical periodontal parameters showed a statistically significant increase in periodontitis groups compared to the control group (p < 0.05). 8-OHdG salivary levels were significantly higher in both periodontitis groups compared to the control group. The salivary FOXO1 levels were significantly lower in both periodontitis groups compared to the control group. Salivary FOXO1 level had a low-grade negative correlation with BOP and salivary 8-OHdG level. CONCLUSIONS: While reactive oxygen species increase in periodontal inflammation, low expression of FOXO1, an important transcription factor for antioxidant enzymes, supports that this molecule plays a vital role in tissue destruction, and FOXO1 can be seen as a potential immune modulator. CLINICAL RELEVANCE: The role of FOXO1 in supporting antioxidant defense may suggest that FOXO1 is a candidate target for periodontitis treatment.

The impact of electronic cigarettes on peri-implant health: A systematic review and meta-analysis.

OBJECTIVES: Recent literature suggests that the use of electronic cigarette (e-cigarette) is a substantial contributing factor to the unsuccessful outcomes of dental implant procedures. Our aim was to systematically review the effect of e-cigarette use on clinical (PI, PD, BOP), radiographic (bone loss), and immunologic (IL-1ß) peri­implant parameters. DATA: Main search terms used in combination: electronic cigarette, peri­implantitis, vaping. SOURCES: An electronic search was undertaken for MEDLINE, EMBASE, COCHRANE, and SCOPUS databases between 2017 and 2023. STUDY SELECTION: The study protocol was developed according to PRISMA guidelines, and the focus question was formulated according to the PICO strategy. No restriction was accepted regarding language or year to avoid selection bias; the initial database search yielded 49 publications. Following the selection process, only seven studies met the inclusion criteria. Seven studies were statistically analyzed via MedCalc program. A pooled effect was deemed statistically significant if the p-value was less than 0.05. CONCLUSION: Electronic cigarettes cause an increase in probing depth, bone loss, and the level of IL-1ß, one of the bone destruction mediators in the tissues around the implant, and a decrease in bleeding on probing. CLINICAL SIGNIFICANCE: E-cigarette is a potential risk factor for the healing process and the results of implant treatment, similar to cigarettes. Performing clinical research to evaluate the e-cigarette effect on peri­implantitis in an age and gender-match population is needed.

The effect of smoking on clinical and biochemical early healing outcomes of coronally advanced flap with connective tissue graft: Prospective cohort study.

BACKGROUND: This study aimed to determine the effects of smoking on early (≤3 months) clinical outcomes and relevant molecular biomarkers following root coverage surgery. METHODS: Eighteen smokers and 18 nonsmokers, status biochemically verified, with RT1 gingival recession defects were recruited and completed study procedures. All patients received coronally advanced flap plus connective tissue graft. Baseline and 3 month recession depth (RD), recession width (RW), keratinized tissue width (KTW), clinical attachment level (CAL), and gingival phenotype (GP) were recorded. Root coverage (RC) percentage and complete root coverage (CRC) were calculated. Recipient (gingival crevicular fluid) and donor (wound fluid) site VEGF-A, HIF-1α, 8-OHdG, and ANG levels were determined. RESULTS: There were no significant intergroup differences for any baseline or postoperative clinical parameters (P > 0.05), except for whole mouth gingival index (increased in nonsmokers at 3 months; P < 0.05). Compared to baseline, RD, RW, CAL, KTW, and GP significantly improved postoperatively, without significant intergroup differences. There were no significant intergroup differences for RC (smokers = 83%, nonsmokers = 91%, P = 0.069), CRC (smokers = 50%, nonsmokers = 72%, P = 0.177), and CAL gain (P = 0.193). The four biomarker levels significantly increased postoperatively (day 7; P ≤ 0.042) in both groups and returned to baseline (day 28) without significant intergroup differences (P > 0.05). Similarly, donor site parameters were not different between groups. Strong correlations, consistent over time, were found between biomarkers implicated in angiogenesis (VEGF-A, HIF-1α, and ANG). CONCLUSIONS: The early (3 month) clinical and molecular changes after root coverage surgery utilizing a coronally advanced flap plus connective tissue graft are similar between smokers and nonsmokers.

The relationship of peri-implant soft tissue wound healing with implant cover screw design: Cross-sectional study.

INTRODUCTION: Dental implants are frequently preferred method for oral rehabilitation all over the world. The incidence of various complications such as incorrect prosthesis, peri-implant mucositis, and peri-implantitis is high; premature loss of implants is encountered due to osteointegration process not being completed for some unexplained reasons. However, there is no study in the literature examining the nonfunctional period of implants. Closure screws of different implant companies have different designs like surface properties, and areas, where closure screws sit, are important reservoirs for microorganism colonization. Our study aims to evaluate the inflammatory response, epithelial maturation, and epithelial-connective tissue interaction around closure screws. METHODS: For this purpose, 52 implants belonging to five different implant companies were included in the study. Tissues removed over the cover screw during fitting of healing caps were used as biopsy material and for epithelial proliferation Ki-67, for epithelium-connective tissue interaction Syndecan-1, and for macrophage activation CD-68 expressions were evaluated by immunohistochemical analysis. Scanning electron microscopy (SEM) analyzes were performed to evaluate the presence of gap between the implant and the cover screw. RESULTS: As a result of our study, intensity of subepithelial inflammation between groups wasn't statistically different. Differences in CD-68 and Syndecan-1 levels were obtained at the lamina propria level. H score of CD-68 was statistically significantly different in epithelium (p = 0.032), and H score of Syndecan-1 was different in lamina propria (p = 0.022). There wasn't a statistically significant difference between the groups for Ki-67 (p = 0.151). CONCLUSION: Our study results indicate that in addition to the implant surface morphology, the design of the closure screws is important in the inflammatory response and epithelial maturation that develops during wound healing. Although the inflammatory response is required for healing, osteointegration, and implant survival, further investigation is needed to investigate the relationship between initial neck resorption and closure screws with radiographic and microbiological examinations.

Wnt signaling in periodontitis.

OBJECTIVE: This study aimed to evaluate the Wnt/ß-catenin signaling pathway activity in gingival samples obtained from patients with periodontitis. MATERIALS AND METHODS: Fifteen patients with stage III grade B (SIIIGB) and eleven with stage III grade C (SIIIGC) periodontitis were included and compared to 15 control subjects. ß-Catenin, Wnt 3a, Wnt 5a, and Wnt 10b expressions were evaluated by Q-PCR. Topographic localization of tissue ß-catenin, Wnt 5a, and Wnt 10b was measured by immunohistochemical analysis. TNF-α was used to assess the inflammatory state of the tissues, while Runx2 was used as a mediator of active destruction. RESULTS: Wnt 3a, Wnt 5a, and Wnt 10b were significantly higher in gingival tissues in both grades of stage 3 periodontitis compared to the control group (p < 0.05). ß-Catenin showed intranuclear staining in connective tissue in periodontitis, while it was confined to intracytoplasmic staining in epithelial tissue and the cell walls in the control group. Wnt5a protein expression was elevated in periodontitis, with the most intense staining observed in the connective tissue of SIIIGC samples. Wnt10b showed the highest density in the connective tissue of patients with periodontitis. CONCLUSIONS: Our findings suggested that periodontal inflammation disrupts the Wnt/ß-catenin signaling pathway. CLINICAL RELEVANCE: Periodontitis disrupts Wnt signaling in periodontal tissues in parallel with tissue inflammation and changes in morphology. This change in Wnt-related signaling pathways that regulate tissue homeostasis in the immunoinflammatory response may shed light on host-induced tissue destruction in the pathogenesis of the periodontal disease.

Expression of tight junction proteins in smokers and non-smokers with generalized Stage III periodontitis.

OBJECTIVE: This study aims to evaluate the gingival crevicular fluid (GCF) levels of tumor necrosis factor-α (TNF-α), zonula occludens-1 (ZO-1), occludin (Occ), and tricellulin (Tric) in periodontitis, as well as their alterations due to smoking. BACKGROUND: Tight junctions (TJ), which consist of transmembrane and cytoplasmic scaffolding proteins, connect the epithelial cells of the periodontium. Occ, claudins, junctional adhesion molecules, and Tric are transmembrane TJ proteins found at the cell membrane. The transmembrane TJ proteins and the intracellular cytoskeleton are directly linked by cytoplasmic scaffolding proteins such as ZO-1. Although the functions and locations of these molecules have been defined, their behavior in periodontal inflammation is unknown. METHODS: The study included four groups: individuals with periodontal health without smoking (C; n = 31), individuals with generalized Stage III periodontitis without smoking (P; n = 28), individuals with periodontal health while smoking (CS; n = 22), and individuals with generalized Stage III periodontitis while smoking (PS; n = 18). Clinical periodontal parameters were recorded, and enzyme-linked immunosorbent assay (ELISA) was used to examine ZO-1, Occ, Tric, and TNF-α levels in GCF. RESULTS: In the periodontitis groups, clinical parameters were significantly higher (p < .001). The site-specific levels of TNF-α, ZO-1, Tric, and Occ in the P group were statistically higher than those in the other groups (p < .05). TNF-α, probing pocket depth (PPD), and bleeding on probing (BOP) exhibited positive correlations with all TJ proteins (p < .005). CONCLUSIONS: Smoking could potentially affect the levels of epithelial TJ proteins in the GCF, thereby potentially playing a significant role in the pathogenesis of the periodontal disease.

Asymmetric and symmetric dimethylarginine gingival crevicular fluid levels in periodontitis.

OBJECTIVE: This study aimed to evaluate the level of ADMA (asymmetric dimethylarginine), SDMA (symmetric dimethylarginine), and IL-1ß (Interleukin-1ß) in gingival crevicular fluid (GCF) from periodontitis patients and control subjects. BACKGROUND: ADMA and SDMA are potentially hazardous non-proteinogenic amino acids that limit nitric oxide (NO) synthesis and have many functions in various human disorders. ADMA causes a structural change in nitric oxide synthase, while SDMA blocks arginine cell uptake. Increased plasma ADMA has been widely recognized as a "trigger" initiating impaired NO bioavailability and vascular dysfunction, which ultimately leads to oxidative stress. METHODS: Twenty-five patients with periodontitis (P) (Stage III, Grade C, n = 25) and 20 control (C) subjects were included in the study. The IL-1ß level of GCF was measured by enzyme immunoassay (ELISA) and ADMA and SDMA by liquid chromatography-mass spectrometry (LC-MS/MS). RESULTS: Periodontitis patients had higher clinical parameters than controls (p < .001). Levels of IL-1ß, ADMA and SDMA GCF were statistically significantly higher in group P than in group C (respectively; p = .003, p < .0001, p < .0001). There was no difference in the ADMA/SDMA ratio (p = .312) between the groups. There were significant positive correlations between clinical periodontal parameters and IL-1ß, ADMA, and SDMA levels (p < .05). ADMA and SDMA levels were significantly correlated with IL-1ß (p < .05). CONCLUSIONS: These findings suggest that ADMA and SDMA may be involved in the pathogenesis of the periodontal disease.

Evaluation of salivary and serum methylated arginine metabolites and nitric oxide synthase in advanced periodontitis patients.

OBJECTIVES: Methylated arginine metabolites and nitric oxide synthase (NOS) play a critical role in regulating endothelial function. The aim of this study was to determine levels of NOS, and methylated arginine metabolites (ADMA, SDMA, homoarginine, arginine, and L-NMMA) and IL-6 in serum and saliva in patients with advanced periodontal diseases and identify their association with clinical parameters. MATERIALS AND METHODS: The study consisted of two groups: healthy individuals (control: n = 24), and generalized Stage III Grade B periodontitis (P: n = 21). Clinical periodontal parameters (probing pocket depth, bleeding on probing, clinical attachment level) were recorded. IL 6 and NOS levels in saliva and serum were analyzed by enzyme-linked immunosorbent assay (ELISA). ADMA, SDMA, homoArg, arginine, and L-NMMA in saliva and serum were analyzed by liquid chromatography-mass spectrometry (LC MS/MS). RESULTS: Clinical parameters were significantly higher in the periodontitis group (p < 0.001). In periodontitis group, NOS, ADMA, and arginine levels in saliva were statistically significantly higher than control group (p < 0.05). Serum levels of SDMA were statistically significantly lower, and IL-6 was statistically significantly higher in P group than C group (p < 0.05). ADMA, NOS, and arginine levels were significantly positive correlated with all clinical periodontal parameters (p < 0.05). CONCLUSIONS: These findings suggest that there is a relationship between severity of periodontal disease and endothelial dysfunction by means of ADMA. Salivary ADMA may be related with periodontal inflammation. CLINICAL RELEVANCE: ADMA levels in periodontal inflammation are associated with endothelial dysfunction. According to the results of our study, periodontal inflammation is effective on both local and systemic methylated arginine metabolites and nitric oxide synthase levels. This may shed light on the relationship between periodontal disease and systemic status.

A disintegrin-like and metalloproteinase with thrombospondin-1 (ADAMTS-1) levels in gingival crevicular fluid correlate with vascular endothelial growth factor-A, hypoxia-inducible factor-1α, and clinical parameters in patients with advanced periodontitis.

BACKGROUND: ADAMTS (a disintegrin-like and metalloproteinase with thrombospondin) are a family of proteinases that are structurally similar to the family of matrix metalloproteinases with critical roles in damage and repair of the extracellular matrix. Their functions are closely related to inflammation, hypoxia, and vascularization. Our aim was to determine levels of ADAMTS-1 in gingival crevicular fluid (GCF) in patients with advanced periodontal diseases and identify their association with hypoxia-inducible factor-1alpha (HIF-1α), vascular endothelial growth factor (VEGF-A), and clinical parameters of periodontitis. METHODS: The study consisted of three groups: healthy individuals (control; n = 20), generalized chronic periodontitis (CP; n = 21), and generalized aggressive periodontitis (GAgP; n = 20). Clinical parameters were measured. Levels of ADAMTS-1, VEGF-A, and HIF-1α in GCF and serum were quantified by enzyme-linked immunosorbent assay (ELISA) and reported as total amounts and concentration. RESULTS: ADAMTS-1 total amount in GCF were significantly higher in patients with CP and GAgP compared with healthy individuals (P < 0.05). HIF-1α total amount in GCF were also higher in periodontitis groups compared with the control group (P < 0.05). GCF total VEGF-A content was significantly higher in the GAgP group compared with the CP and the controls (respectively; P = 0.023, P = 0.003). There was a significant correlation between ADAMTS-1, VEGF-A, and HIF-1α levels in the GCF and clinical periodontal parameters (probing depth [PD], bleeding on probing [BOP], and clinical attachment loss (CAL); P < 0.05). CONCLUSION: ADAMTS-1 may play a role in advanced periodontal disease pathogenesis in correlation with tissue hypoxia and vascularization.