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Aim: Emerging evidence points to a two-way relationship between periodontitis and dietary choices and, thus, nutrition. This study aimed to assess the potential cause-effect relationship between the periodontitis stage, loss of functional tooth units (FTUs), masticatory function, and intake of different food groups using path analysis., Materials and Methods: A single calibrated examiner determined the periodontitis stage of a consecutive sample of 241 Chinese subjects reporting for tooth replacement. Their masticatory function was quantified by the mixing ability of a two-colour chewing gum. Validated food frequency questionnaires were used to calculate the intake of 33 food group items by an experienced calibrated rater. After verification of assumptions, visual structural equation modeling was performed with Amos 23. The consistency of results and the potential modifying effect of age were assessed in 9043 subjects from the NHANES database., Results: Highly significant models were constructed using periodontitis stage and age as exogenous factors. Periodontitis stage diagnosis significantly affected the number of posterior FTUs and oral health-related quality of life (OHRQoL, path coefficient [PC] = -0.55 and -0.20, p < .05, respectively). In the model, FTUs also had an independent effect on OHRQoL (PC = 0.23, p < .05). FTUs determined the level of masticatory function (PC = -0.38, p < .05), which in turn affected vegetable intake but not fruit or meat intake (PC = -0.18, p < .0.5, PC = 0.06, NS and PC = 0.11, NS, respectively). The effect of age was significant for vegetable and meat intake and was also correlated with periodontitis stage diagnosis. Analysis of the NHANES database confirmed the negative impact of periodontitis on the number of occluding pairs and vegetable consumption for the 18-44, 45-60 and >60 age groups., Conclusions: Periodontitis showed a potential cause-effect pathway affecting vegetable intake across cultures and age groups. The size of the effect is potentially of clinical and public health significance. Additional studies, including intervention trials, are required to test this potential mechanism linking oral health to nutrition., (© 2024 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Xerostomia emerges as a consequence of salivary gland hypofunction, and seriously compromises the integrity of hard and soft oral tissues, whileperiodontitis is an infectious disease characterized by biofilm accumulation, inflammation and alveolar bone resorption., Aim: The aim this study was to compare the deleterious effects caused by experimental hyposalivation, periodontitis, and the combination of both on periodontal tissues and mandibular biomechanics in rats., Materials and Method: Hyposalivation (group H) was induced through bilateral submandibulectomy. Periodontitis (group EP) was induced by injecting LPS (1 mg/ml) into the gingiva of the first lower molars. A third group was subjected to both conditions (group H+EP). Alveolar bone loss was evaluated by micro-computed tomography and histomorphometric analysis, and gingival inflammatory mediators were assessed by specific techniques. Biomechanical properties were evaluated in mandible., Results: Alveolar bone loss increased similarly in groups H, EP and H+EP compared to control. Metalloproteinase (MMP2 and MMP9) activity was similar in H and control, but higher in groups EP and H+EP (MMP2: C 9644+2214, EP 34441+3336, H 5818+1532, H+EP 42673+3184; MMP9: C 5792+961, EP 14807+861, H 9295+520, H+EP 4838+1531). The rest of the inflammatory mediators evaluated increased in groups H, EP and H+EP to a greater or lesser extent with respect to the control, although in most cases, they were higher in groups EP and H+EP than in group H. The biomechanical properties of the mandible increased in group H compared to the other three groups., Conclusions: Both hyposalivation and periodontitis cause periodontal damage, but hyposalivation also produces biomechanical alterations, causing more extensive deleterious effects than periodontitis., Competing Interests: The authors declare no potential conflicts of interest regarding the research, authorship, and/or publication of this article., (Copyright© 2024 Sociedad Argentina de Investigación Odontológica.)

Periodontitis is a widespread oral disease accompanied by uncontrolled inflammation-related tissue destruction. Periodontitis is related to various factors. Among them, occlusal trauma can aggravate the severity of periodontitis and has been attracting a great deal of attention. We systematically searched PubMed and Web of Science databases for related articles. Keywords for the search were "mechanical force", "mechanical stress", "occlusal trauma" and "periodontitis". This review focuses on the effect of mechanical forces on periodontitis and discusses the possible pivotal targets participating in this process. We elucidated and summarized 21 articles that reported on our topic. Several biological processes and pathways that participate in enhancing the inflammatory response to mechanical stress have been studied, including the regulation of osteogenesis and osteoclastic resorption balance, Yes-associated protein signaling, induction of collagen destruction, and regulation of programmed cell death. Mechanical force enhances the process of periodontitis in multiple ways. However, currently, no studies have further examined its underlying mechanism. Understanding the specific roles of mechanical forces may assist in the treatment of periodontitis with traumatic occlusal trauma., (© 2023 Wiley Periodicals LLC.)

Periodontitis is a common chronic infection and is associated with cardiovascular disease. This study evaluated whether basic oral care for periodontal disease could improve endothelial function in patients with acute coronary syndrome (ACS).This study enrolled 54 patients with acute coronary syndrome admitted to Kagoshima City Hospital and who had undergone percutaneous coronary intervention. Flow-mediated endothelium-dependent dilatation (FMD) was measured before discharge (initial FMD) and at 8 months after percutaneous coronary intervention (follow-up FMD). The following periodontal characteristics were measured: periodontal pocket depth (PPD, mm), plaque control record (%), and bleeding on probing (%). All patients received basic oral care instructions from dentists. The oral health condition was generally poor in the participants and there were 24 patients (44.4%) who had severe PPD. Despite the intervention of basic oral care, the periodontal characteristics did not improve during the study period; initial FMD and follow-up FMD did not significantly differ (4.38 ± 2.74% versus 4.56 ± 2.51%, P = 0.562). However, the follow-up FMD was significantly lower in patients with severe PPD (≥ 6.0 mm, n = 24) than in patients without severe PPD (≤ 5.0 mm, n = 30) (FMD: 3.58 ± 1.91% versus 5.37 ± 2.67%, P = 0.007). FMD tended to be worse in patients with severe PPD than in patients without severe PPD (ΔFMD: -0.55 ± 2.12 versus 0.81 ± 2.77 %, P = 0.055). In conclusion, during the use of basic oral care, endothelial function improved in patients without severe PPD, while it worsened in patients with severe PPD.

Objective: To study the preventive effect of Lactobacillus helveticus ( L. helveticus ) on periodontitis induced by Aggregatibacter actinomycetemcomitans ( A. actinomycetemcomitans ) in rats., Methods: Eighteen 8-week-old female rats were randomly divided into three groups: Sham group, Trehalose group, and L. helveticus SBT2171 (LH2171) group. We measured the distance of the cementoenamel junction-alveolar bone crest (CEJ-ABC) to evaluate alveolar bone resorption. Hematoxylin-eosin staining was used to observe the histopathological changes of rat hemimaxillary tissues. We detected the expression of β -defensins, tumor necrosis factor- α (TNF- α ), interleukin- (IL-) 1 β , and IL-6 and the number of A. actinomycetemcomitans in rat gingival tissues by quantitative reverse transcriptase polymerase chain reaction. The levels of IL-1 β , IL-6, and TNF- α in rat gingival tissues were also measured by enzyme-linked immunosorbent assay., Results: Compared with the Trehalose group, the distance of CEJ-ABC was prominently reduced and alveolar bone resorption was notably improved in the LH2171 group. And the infiltration of inflammatory cells in the hemimaxillary tissue decreased obviously, periodontal fibers were arranged neatly, connective tissue small blood vessels proliferated, and the number of A. actinomycetemcomitans reduced significantly in the LH2171 group. In addition, the mRNA expression and release of inflammatory factors in the gingival tissues in the LH2171 group were notably lower than those in the Trehalose group. On the 21st and 36th day, the expression of β -defensins in the gingival tissue of the LH2171 group increased significantly., Conclusion: L. helveticus improves alveolar bone resorption and increases the expression of β -defensins thereby inhibiting the number of A. actinomycetemcomitans and thus prevents periodontitis., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Ru Jia et al.)

Purpose: There are no data regarding periodontal derangements in patients with adrenal incidentalomas (AI). We assessed the frequency and severity of periodontitis in patients with AI [non-functioning adrenal incidentaloma (NFAI) and possible autonomous cortisol secretion (ACS)] and compared with individuals with normal adrenal., Methods: A cross-sectional study evaluated thirty-five individuals with AI and 26 controls. NFAI and possible ACS diagnosis was based on the current guidelines: NFAI [cortisol levels after 1 mg dexamethasone suppression test (1 mg-DST) ≤ 1.8 µg/dL (≤ 50 nmol/L)]; possible ACS [cortisol levels after 1 mg-DST 1.9-5.0 µg/dL (51-138 nmol/L)]. Sociodemographic data were collected, and a full-mouth periodontal evaluation was performed., Results: There was no significant difference between groups regarding age, sex, income, ethnicity, education level, smoking, body mass index, dysglycemia, and arterial hypertension. Patients with AI exhibited worse periodontal conditions than controls for the following periodontal clinical parameters: mean percentage of probing pocket depth (PPD) and clinical attachment level (CAL) ≥ 5 mm (p < 0.001 and p = 0.006, respectively). Patients with NFAI and possible ACS showed higher gingival bleeding index (p = 0.014), bleeding on probing (p < 0.001), and CAL (p < 0.001) means compared to controls. The frequencies of periodontitis were 72.7% in patients with NFAI, 84.6% in possible ACS, and 30.8% in controls (p = 0.001). Periodontitis was more severe in patients with possible ACS than NFAI and controls. Patients with NFAI and possible ACS exhibited odds ratio for periodontitis of 4.9 (p = 0.016) and 8.6 (p = 0.02), respectively., Conclusion: Patients with AI have higher frequency and severity of periodontitis than controls. The presence of AI was an independent predictive factor for periodontitis., (© 2021. Italian Society of Endocrinology (SIE).)

Increase of sympathetic activity has been known to exacerbate osteoporosis through promotion of bone resorption. However, it is largely unknown about involvement of sympathetic activity in exacerbation of periodontitis. In this study, we investigated whether α 2 -adrenergic receptor (α 2 -AR) agonist guanabenz which decreases sympathetic activity, attenuates alveolar bone resorption in rats having high sympathetic activity with periodontitis. Volumes of residual alveolar bone and attachment levels in periodontium were examined using micro-computed tomography and hematoxylin-eosin staining, respectively. Furthermore, osteoclast numbers per bone surface and osteoclast surface per bone surface were measured using tartrate-resistant acid phosphatase staining. To examine the suppressive effects of guanabenz on pro-inflammatory cytokines, expression levels of tyrosine hydroxylase (TH), TNF-α, IL1-β, and IL-6 in periodontium were measured using immunohistostaining. Administration of guanabenz attenuated loss of alveolar bone and attachment levels in rats having high sympathetic activity. Furthermore, its administration suppressed osteoclast numbers in rats having high sympathetic activity. TH, TNF-α, IL-1β, and IL-6 positive cells in periodontium in rats treated with guanabenz for 12 weeks, were lower than those in control rats having high sympathetic activity. This study demonstrated administration of α 2 -AR agonist guanabenz attenuates alveolar bone resorption through decrease of sympathetic activity in rats., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2021 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Periodontitis, one of the most common chronic inflammatory diseases, affects the quality of life. Osteogenesis plays an important role in the disease. There is a connection between hydrogen sulfide (H 2 S) and periodontitis, but according to the study has been published, the precise role of H 2 S in inflammation remains in doubt. The main reason for the lack of research is that H 2 S is an endogenous gasotransmitter, difficult to discern through testing. So, we synthesized a novel fluorescence probe which can detect H 2 S in vitro. By using the novel H 2 S fluorescence probe, we found that H 2 S changes in osteoblasts mainly by cystathionine-γ-lyase, and H 2 S increases under LPS stimulation. H 2 S could be a potential marker for diagnosis of inflammatory diseases of bone, and might help deepen studies of the changes of H 2 S level and promote the progression on the researches about pathogenesis of periodontitis., (© 2021. The Author(s).)

Diabetes and periodontitis are two of the most prevalent diseases worldwide that negatively impact the quality of life of the individual suffering from them. They are part of the chronic inflammatory disease group or, as recently mentioned, non-communicable diseases, with inflammation being the meeting point among them. Inflammation hitherto includes vascular and tissue changes, but new technologies provide data at the intracellular level that could explain how the cells respond to the aggression more clearly. This review aims to emphasize the molecular pathophysiological mechanisms in patients with type 2 diabetes mellitus and periodontitis, which are marked by different impaired central regulators including mitochondrial dysfunction, impaired immune system and autophagy pathways, oxidative stress, and the crosstalk between adenosine monophosphate-activated protein kinase (AMPK) and the renin-angiotensin system (RAS). All of them are the shared background behind both diseases that could explain its relationship. These should be taken in consideration if we would like to improve the treatment outcomes. Currently, the main treatment strategies in diabetes try to reduce glycemia index as the most important aspect, and in periodontitis try to reduce the presence of oral bacteria. We propose to add to the therapeutic guidelines the handling of all the intracellular disorders to try to obtain better treatment success.

Recent studies have supported the relationship between periodontitis and carotid artery calcification (CAC), but still uncertain. This systematic review is aimed at evaluating the association between periodontitis and CAC. The search was conducted in four electronic databases: PubMed, EMBASE, Web of Science, and The Cochrane Library, supplemented by checking references of included articles and related review articles. Eligibility assessment and data extraction were conducted independently. The quality assessment and publication bias analysis were performed. The association between periodontitis and CAC was presented in odd ratio (OR) with 95% confidence interval (CI). Additional outcomes included the percentage of alveolar bone loss in CAC versus non-CAC. Twelve studies were included, and 10 were performed quantity analysis. Periodontitis with secure definition (OR = 2.02, 95%CI = 1.18 - 3.45) and insecure definition (OR = 10.78, 95%CI = 4.41 - 26.34) was associated with CAC. And a higher average percentage of alveolar bone loss (weighted mean difference = 10.84%; 95%CI = 6.40 - 15.48) was also observed in CAC patients compared to non-CAC patients. No significant publication bias was found. The results of this systematic review and meta-analysis revealed a significant relationship between periodontitis and CAC., Competing Interests: The authors report no conflicts of interest related to this study., (Copyright © 2021 Wenxuan Wang et al.)

Purpose: Emerging evidence has indicated that oxidative stress (OS) contributes to periodontitis. Periodontal ligament cells (PDLCs) are important for the regeneration of periodontal tissue. Quercetin, which is extracted from fruits and vegetables, has strong antioxidant capabilities. However, whether and how quercetin affects oxidative damage in PDLCs during periodontitis remains unknown. The aim of this study was to assess the effects of quercetin on oxidative damage in PDLCs and alveolar bone loss in periodontitis and underlying mechanisms., Materials and Methods: The tissue block culture method was used to extract human PDLCs (hPDLCs). First, a cell counting kit 8 (CCK-8) assay was used to identify the optimal concentrations of hydrogen peroxide (H 2 O 2 ) and quercetin. Subsequently, a 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA) probe, RT-qPCR, Western blotting and other methods were used to explore the effects of quercetin on OS in hPDLCs and the underlying mechanism. Finally, quercetin was administered to mice with periodontitis through gavage, and the effect of quercetin on the level of OS and alveolar bone resorption in these mice was observed by immunofluorescence, microcomputed tomography (micro-CT), hematoxylin and eosin staining (H&E) staining and so on., Results: Quercetin at 5 μM strongly activated NF-E2-related factor 2 (NRF2) signaling, alleviated oxidative damage and enhanced the antioxidant capacity of hPDLCs. In addition, quercetin reduced cellular senescence and protected the osteogenic ability of hPDLCs. Finally, quercetin activated NRF2 signaling in the periodontal ligaments, reduced the OS level of mice with periodontitis, and slowed the absorption of alveolar bone in vivo., Conclusion: Quercetin can increase the antioxidant capacity of PDLCs and reduce OS damage by activating the NRF2 signaling pathway, which alleviates alveolar bone loss in periodontitis., Competing Interests: The authors have no conflicts of interest to declare., (© 2021 Wei et al.)

OBJECTIVE: Inflammation, oxidative stress, and endothelial dysfunction are known to contribute to ischemia-reperfusion injury. Remote ischemic preconditioning (RIPC) protects from endothelial dysfunction and the damage induced by ischemiareperfusion. Using intensive periodontal treatment (IPT), an established human model of acute systemic inflammation, we investigated whether RIPC prevents endothelial dysfunction and modulates systemic levels of inflammation and oxidative stress. APPROACH AND RESULTS: Forty-nine participants with periodontitis were randomly allocated to receive either 3 cycles of ischemia-reperfusion on the upper limb (N=24, RIPC) or a sham procedure (N=25, control) before IPT. Endothelial function assessed by flow-mediated dilatation of the brachial artery, inflammatory cytokines, markers of vascular injury, and oxidative stress were evaluated at baseline, day 1, and day 7 after IPT. Twenty-four hours post-IPT, the RIPC group had lower levels of IL-10 (interleukin-10) and IL-12 (interleukin-12) compared with the control group (P<0.05). RIPC attenuated the IPTinduced increase in IL-1β (interleukin-1β), E-selectin, sICAM-3 (soluble intercellular adhesion molecule 3), and sTM (soluble thrombomodulin) levels between the baseline and day 1 (P for interaction <0.1). Conversely, oxidative stress was differentially increased at day1 in the RIPC group compared with the control group (P for interaction <0.1). This was accompanied by a better flow-mediated dilatation (mean difference 1.75% [95% CI, 0.428–3.07], P=0.011). After 7 days from IPT, most of the inflammatory markers, endothelial-dependent and -independent vasodilation, were similar between groups. CONCLUSIONS: RIPC prevented acute endothelial dysfunction by modulation of inflammation and oxidation processes in patients with periodontitis following exposure to an acute inflammatory stimulus. REGISTRATION: URL: https://clinicaltrials.gov/ct2/show/NCT03072342; Unique identifier: NCT03072342.

Here, we assess the association between homocysteine (Hcy) serum levels and periodontal status in a large representative sample of the National Health and Nutrition Examination Survey (NHANES). Using the 2001-2002 and 2003-2004 NHANES databases, participants with a periodontal examination, medical self-reported data, blood pressure (BP) and blood samples to determine complete blood count, C-reactive protein (CRP) and Hcy levels. We then calculated the periodontal inflamed surface area (PISA) and the periodontal epithelial surface area (PESA). Multivariable regression analysis explored the association between Hcy, periodontal measures and BP. Mediation analysis was performed to understand the effect of PISA and PESA in the link between Hcy and BP. 4021 participants fulfilled the inclusion criteria. Hcy levels showed significant correlations with systolic BP, diastolic BP, PISA, PESA and age. PESA showed to be significantly associated with Hcy both for the crude and adjusted models ( p < 0.01), but not PISA ( p > 0.05). In the association of Hcy with systolic BP, PISA significantly mediated 17.4% and PESA 0.9%. In the association of Hcy with diastolic BP, PISA significantly mediated 16.3% and PESA 47.2%. In conclusion, Hcy and periodontitis are associated. Further, both PISA and PESA significantly mediated the association of Hcy with systolic BP and diastolic BP. Future studies shall deepen the mechanisms by which Hcy levels increase in a clinical situation of periodontitis.

[Figure: see text].

Associations of numbers of teeth present and of missing teeth with Alzheimer's disease were cross-sectionally analyzed using the National Database of Health Insurance Claims and Specific Health Checkups of Japan. Dental care claims data of patients aged 60 years or older diagnosed with periodontitis (n = 4,009,345) or missing teeth (n = 662,182) were used to obtain information about the numbers of teeth present and of missing teeth, respectively, and they were combined with medical care claims data including the diagnosis of Alzheimer's disease. Numbers of teeth present and of missing teeth excluding third molars were calculated using the dental formula in the claims for periodontitis and missing teeth, respectively, and categorized into three groups each. Percentages of subjects treated for Alzheimer's disease with 20-28, 10-19, and 1-9 teeth present were 1.95%, 3.87%, and 6.86%, respectively, in patients diagnosed as having periodontitis, and those treated for Alzheimer's disease with 1-13, 14-27, and 28 missing teeth were 2.67%, 5.51%, and 8.70%, respectively, in patients diagnosed as having missing teeth. Logistic regression models using treatment for Alzheimer's disease as an outcome variable and adjusting for age and sex showed that odds ratios (95% confidence intervals) for patients with 10-19 and 1-9 teeth (reference: 20-28 teeth) were 1.11 (1.10-1.13) and 1.34 (1.32-1.37), respectively, (p<0.001), in patients diagnosed as having periodontitis, and odds ratios (95% confidence intervals) for patients with 14-27 missing teeth and 28 missing teeth (reference: 1-13 missing teeth) were 1.40 (1.36-1.44) and 1.81 (1.74-1.89), respectively, (p<0.001), in patients diagnosed as having missing teeth. In conclusion, the results of the present study using Japanese dental claims data showed that older people visiting dental offices with fewer teeth present and a greater number of missing teeth are more likely to have Alzheimer's disease., Competing Interests: The authors have declared that no competing interests exist.

It is estimated that 560 million people carry an East Asian-specific ALDH2*2 dominant-negative mutation which leads to enzyme inactivation. This common ALDH2 polymorphism has a significant association with osteoporosis. We hypothesized that the ALDH2*2 mutation in conjunction with periodontal Porphyromonas gingivalis bacterial infection and alcohol drinking had an inhibitory effect on osteoblasts and bone regeneration. We examined the prospective association of ALDH2 activity with the proliferation and mineralization potential of human osteoblasts in vitro. The ALDH2 knockdown experiments showed that the ALDH2 knockdown osteoblasts lost their proliferation and mineralization capability. To mimic dental bacterial infection, we compared the dental bony defects in wild-type mice and ALDH2*2 knockin mice after injection with purified lipopolysaccharides (LPS), derived from P. gingivalis which is a bacterial species known to cause periodontitis. Micro-computed tomography (micro-CT) scan results indicated that bone regeneration was significantly affected in the ALDH2*2 knockin mice with about 20% more dental bony defects after LPS injection than the wild-type mice. Moreover, the ALDH2*2 knockin mutant mice had decreased osteoblast growth and more dental bone loss in the upper left jaw region after LPS injection. In conclusion, these results indicated that the ALDH2*2 mutation with alcohol drinking and chronic exposure to dental bacterial-derived toxin increased the risk of dental bone loss.

Periodontitis is an inflammatory disease that affects tooth-supporting tissues. Chronic inflammation can progress to periodontitis, which results in loss of alveolar bone. Asarylaldehyde is a potential substance for bone metabolism present in natural compounds. Here, we propose the application of asarylaldehyde in the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) to prevent bone loss. We investigated the effect of asarylaldehyde on hPDLSCs together with bone differentiation media in vitro. The osteogenic differentiation effect was observed after treatment of hPDLSCs with several concentrations of asarylaldehyde. After 21 days, osteogenic cells were identified by mineralization. We also observed that asarylaldehyde increased the mRNA expression of osteoblast-specific markers in hPDLSCs. Interestingly, asarylaldehyde regulated the levels of alkaline phosphatase (ALP) transcriptional activity through the p38/extracellular-signal-regulated kinase (ERK) signaling pathway. Notably, asarylaldehyde induced hPDLSCs to promote osteogenic differentiation. These results suggest that asarylaldehyde plays a key role in the osteogenic differentiation of hPDLSCs. Asarylaldehyde may be a good candidate for the application of natural compounds in future in periodontal regeneration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The aim of this study was to investigate the effects of exposure to continuous (CH) and intermittent (IH) hypoxia on biomechanical properties of the mandible and periodontal tissue of animals submitted to experimental periodontitis (EP) when applying loads in a hypoxic environment., Methods: Adult female Wistar rats were exposed during 90 days to IH or CH (simulated high altitude of 4200 m above sea level). Fourteen days prior to the euthanasia, EP was induced to half of the animals of each group., Results: Only in the rats with EP, IH decreased the maximum capacity of the mandible to withstand load and the limit of elastic load. Indicators of intrinsic properties of the bone material were significantly reduced by both types of hypoxia in rats with EP. Hypoxia enhanced the alveolar bone loss induced by EP in the buccal side of the mandible, without showing additional effects in lingual or interradicular bone. Hypoxia increased prostaglandin E 2 content in gingival tissue of healthy animals and further elevated the E 2 levels increased by EP., Conclusions: When periodontitis is present, hypoxic stress induces a decrease in mineral properties that ultimately affects the ability of the mandible to resist load, mainly during intermittent exposure to hypoxia. These effects on bone may be related to the higher levels of prostaglandin E 2 reached in the surrounding gingival tissue. The findings of this study may stimulate strategies to prevent unwanted effects of hypoxia on periodontal tissues.

Background: Few studies have been conducted on the relationship between chronic periodontitis and postoperative pneumonia (POP) in patients with lung and esophageal cancer. Furthermore, it remains controversial as to whether improving the periodontal condition of patients with lung and esophageal cancer before surgery reduces the incidence of POP. This retrospective study was conducted to assess the effects of periodontal therapy in patients with lung and esophageal cancer to prevent POP., Methods: A total of 265 patients with lung or esophageal cancer complicated with chronic periodontitis who underwent open thoracotomy between July 2015 and June 2019 were selected and given the choice of being in the experimental or control group. A total of 141 participants in the experimental group received periodontal therapy, and 124 participants in the control group did not receive periodontal therapy. All clinical data of participants in both groups were retrospectively studied to determine the incidence of POP on the 30th day after discharge from hospital., Results: Eight patients in the experimental and six in the control group, respectively, were excluded from the study. It was found that four of the 133 patients suffered from POP in the experimental group (incidence: 3.01%). A total of 18 of 118 patients in the control group had a pulmonary infection (incidence: 15.25%). POP incidence in the experimental group was significantly lower than that in the control group, and in the level analysis of different types of periodontitis, surgical methods, and diseases (p < 0.05)., Conclusions: Periodontal treatment is associated with a lower incidence of POP following lung and esophageal cancer surgery. Improving the periodontal condition of patients helps prevent POP. The presence of periodontitis is an important predisposing factor for POP in patients after open thoracotomy. Periodontal examination and therapy are recommended before the surgical treatment of lung or esophageal cancer., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Periodontitis is a chronic infection initiated by oral bacterial and their virulence factors, yet the severity of periodontitis is largely determined by the dysregulated host immuno-inflammatory response. Baicalein is a flavonoid extracted from Scutellaria baicalensis with promising anti-inflammatory properties. This study aims to clarify the anti-inflammatory and osteogenic effects of baicalein in periodontal ligament cells (PDLCs) treated with lipopolysaccharides (LPS)., Methods: Human PDLCs were incubated with baicalein (0-100 μM) for 2 h prior to LPS challenge for 24 h. MTT analysis was adopted to assess the cytoxicity of baicalein. The mRNA and protein expression of inflammatory and osteogenic markers were measured by real-time polymerase chain reaction (PCR), western blot and enzyme-linked immunosorbent assay (ELISA) as appropriate. Alkaline phosphatase (ALP) and Alizarin red S (ARS) staining were performed to evaluate the osteogenic differentiation of PDLCs. The expression of Wnt/β-catenin and mitogen-activated protein kinase (MAPK) signaling related proteins was assessed by western blot., Results: MTT results showed that baicalein up to 100 μM had no cytotoxicity on PDLCs. Baicalein significantly attenuated the inflammatory factors induced by LPS, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), matrix metalloprotein-1 (MMP-1), MMP-2 and monocyte chemoattractant protein 1 (MCP-1) at both mRNA and protein level. Moreover, MAPK signaling (ERK, JNK and p38) was significantly inhibited by baicalein, which may account for the mitigated inflammatory response. Next, we found that baicalein effectively restored the osteogenic differentiation of LPS-treated PDLCs, as shown by the increased ALP and ARS staining. Accordingly, the protein and gene expression of osteogenic markers, namely runt-related transcription factor 2 (RUNX2), collagen-I, and osterix were markedly upregulated. Importantly, baicalein could function as the Wnt/β-catenin signaling activator, which may lead to the increased osteoblastic differentiation of PDLCs., Conclusions: With the limitation of the study, we provide in vitro evidence that baicalein ameliorates inflammatory response and restores osteogenesis in PDLCs challenged with LPS, indicating its potential use as the host response modulator for the management of periodontitis.

Aim: To assess the effect of periodontal treatment (PT) on glomerular filtration rate (GFR), systemic inflammation, or mortality in patients with chronic kidney disease (CKD)., Methods: A literature search was performed on PubMed and Web of Science databases on articles published until December 2019. The PRISMA guidelines were used throughout the manuscript., Results: Of the total studies found, only 18 met the inclusion criteria; four retrospective and 14 prospective studies (including 3 randomized controlled trials-RCT). After PT, 3 studies investigated GFR, 2 found significant improvement; 11 (including 2 RCTs) investigated C-reactive protein levels, 9 found a significant improvement (including the 2 RCTs); 5 (including 3 RCTs) investigated Interleukine-6 level, 4 found a significant improvement (including 2 RCTs) and 2 studies evaluated mortality, one (retrospective study) found a significant difference., Conclusions: Within the limitations of the present study, PT seems to improve CKD status, especially by reducing the systemic inflammation. Further RCTs are needed to confirm the results and specifically assess the influence of different types of PT in CKD patients. Taking into consideration the ability of PT to prevent further tooth loss and denutrition, early management of periodontitis is extremely important in patients with impaired renal function., Competing Interests: The authors have declared that no competing interests exist.

Aims: It has been shown that periodontitis, can be modified by systemic changes, including behavioral factors, such as diet. Caloric restriction is one of the dietary therapeutic strategies indicated for obesity. It is associated with several benefits, among them, modulation of the inflammatory response. The aim of this study was to verify whether caloric restriction in obese rats changes the progression of experimental ligature-induced periodontitis., Materials and Methods: Forty-eight Wistar rats were used for 24 weeks and initially fed with cafeteria diet during 12 weeks. The animals were divided into four groups according to the caloric restriction and experimental periodontitis. The cotton thread was placed around the mandibular first molars, for 15 days, before the end of the experiment. Rats submitted to caloric restriction received, from the 13th week of the experimental protocol, 70% of the food intake compared to the ad libitum animals of other study of the our research group. Alveolar bone loss was assessed using macroscopic morphometric analysis. Analyzes of clinical periodontal measures, biometrics, serum biomarkers and biochemical parameters were performed., Key Findings: Caloric restriction decreased the alveolar bone loss in the periodontitis group when compared to the group that received a cafeteria diet with periodontitis. Moreover, the results demonstrate the improvement in the glycemic profile, without prejudice to bone tissue biomarkers., Significance: Based on the results, caloric restriction reduces the progression of alveolar bone loss in rats with experimental periodontitis, in addition to presenting benefits in biometric data, decreasing both glycemic profile and clinical periodontal measures., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Periodontitis is a chronic inflammatory disease that results in the destruction of periodontal soft tissue and the resorption of alveolar bone. Evidence indicates that in diabetic patients, hyperglycemia suppresses periodontal ligament stem cell (PDLSC) functions and leads to difficulties in periodontal repair. The present study aimed to explore the mechanisms by which high-glucose concentrations aggravate cell viability reduction in human CD146-positive PDLCs (CD146 + PDLCs) under tumor necrosis factor-alpha (TNF-alpha) induction. CD146 + PDLCs were isolated from periodontal ligament tissues and treated in the absence or presence of 10 ng/ml of TNF-alpha and 30 mM glucose. Cell viability was detected using Cell Counting Kit-8 assays and Luminescent Cell Viability Assays. Western blotting and real-time polymerase chain reaction were performed to determine tumor necrosis factor-alpha receptor-1 (TNFR-1) protein and messenger RNA expression. Bisulfite and MassArray methylation analyses were used to analyze the methylation status of the TNFR-1 gene. Our results indicated that cell viability was reduced after treatment with a combination of both high-glucose concentration and TNF-alpha. Treatment with 30 mM glucose suppressed DNA methyltransferase (DNMT) activities and DNMT1 protein expression, and this was accompanied by the upregulation of TNFR-1. Additionally, we found that the CpG island located within the TNFR-1 gene was hypomethylated under 30 mM glucose conditions. S-adenosylmethionine, an established methyl donor, reversed TNFR-1 upregulation and restored cell viability against high-glucose concentration and TNF-alpha. In conclusion, the present findings suggest that high-glucose-induced CpG island hypomethylation within the TNFR-1 gene plays an essential role in TNFR-1 upregulation, and this further enhances the cell viability reduction of CD146 + PDLCs caused by TNF-alpha., (© 2020 International Federation for Cell Biology.)

Aims: Oral cavity pathogens play an important systemic role, modulating the development of several diseases. Periodontitis is a very common oral disease associated with dental biofilm. It is characterized by gum inflammation, periodontal ligament degeneration, dental cementum and alveolar bone loss. Studies point to the association between maternal periodontitis and adverse outcomes during pregnancy. However, they did not evaluate the impact of maternal periodontitis in the offspring. Thus, our objective was to investigate the effects of maternal periodontitis in the immune system of offspring., Material and Methods: For this evaluation we induced acute lung injury in rat pups. Pregnant rats were submitted or not to periodontitis by ligature technique. Thirty days after the birth, offspring was submitted to acute lung inflammation by administration of lipopolysaccharide (LPS, Salmonella abortus equi, 5 mg/kg, ip)., Key Findings: Our results showed that maternal periodontitis increased myeloperoxidase activity, the levels of TNF-alpha and IL-17A in the bronchoalveolar fluid, the gene expression of TNF-alpha, IL-17A, and cyclooxygenases 1 and 2. In addition, maternal periodontitis did not alter the number of leukocytes migrated into the lung, tracheal responsiveness, expression of TLR4 and NF-KB translocation., Significance: This study showed prenatal programming of the immune response induced by maternal periodontitis, and reinforces the importance of oral health care during pregnancy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Periodontitis is a multifactorial inflammatory disease that can cause tooth loss and contribute to systemic inflammation. It is suggested that periodontitis may be associated with the development of glaucoma. Based on data from Taiwan's National Health Insurance Research Database, a retrospective cohort study was conducted to investigate the risk of developing glaucoma in patients with periodontitis. The periodontitis cohort consisted of newly diagnosed adult patients (n = 194,090, minimum age = 20 years) between 2000 and 2012. The comparison group included age-, gender-, and diagnosis date-matched people without periodontitis (n = 194,090, minimum age = 20 years). Incident glaucoma was monitored until the end of 2013. Hazard ratios (HRs) with confidence intervals (CIs) were established based on the Cox proportional hazard models. The risk of developing glaucoma was higher in patients with periodontitis than those without periodontitis (31.2 vs. 23.3 patients per 10,000 person-years, with an adjusted HR of 1.26 [95% CI 1.21-1.32]). A high risk was evident even after stratifying by age (adjusted HRs = 1.34 [1.26-1.44] for ages 20-49, 1.24 [1.13-1.36] for ages ≥ 65, and 1.20 [1.12-1.29] for ages 50-64 years), sex (adjusted HRs = 1.33 [1.24-1.41] and 1.21 [1.14-1.28] for men and women, respectively), presence of comorbidity (adjusted HRs = 1.38 [1.29-1.47] and 1.18 [1.12-1.25] for without and with comorbidity, respectively), and corticosteroid use (adjusted HRs = 1.27 [1.21-1.33] and 1.21 [1.08-1.35] for without and with corticosteroid use, respectively). Specifically, patients with periodontitis exhibited a significantly high risk of primary open-angle glaucoma (adjusted HR = 1.31 [1.21-1.32]) but not for primary closed-angle glaucoma (adjusted HR = 1.05 [0.94-1.17]). People with periodontitis are at a greater risk of glaucoma than individuals without periodontitis. Ocular health should be emphasized for such patients, and the underlying mechanisms need further investigation.

Background and objectives: People with Parkinson's disease (PD) may be at risk of having bad periodontal status. A consistent periodontal examination is critical to investigate how it impacts on PD quality of life. We aimed to assess the periodontal status of people with PD, and its association with quality of life and self-perceived xerostomia. Materials and Methods: To this end, from February to March 2020, we consecutively enrolled 28 PD individuals, and motor and non-motor symptoms of PD were assessed using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). We performed full-mouth periodontal examination and gathered information on self-perceived quality of life in PD, oral health impact profile (OHIP-14) and xerostomia. Results: The prevalence of periodontitis was 75.0% and most cases were identified as severe (46.4%). Upper extremity rigidity, hand posture and kinetic tremors were significantly correlated with worse periodontal status. PDQ-8 showed to be correlated with self-perceived oral health-related quality of life and xerostomia levels. Conclusions: This group of people with PD had a high prevalence of periodontitis. Deteriorated levels of the upper extremities in advanced stages of PD were associated with worse periodontal status and hygiene habits. Quality of life in PD appears to be associated with self-perceived OHRQoL and xerostomia.

Background: The relationship between poor oral health conditions and cognitive decline is unclear., Objective: To examine the association between oral health and cognition in humans and rats., Methods: In humans: a cross-sectional study was conducted. Cognitive levels were evaluated by the Mini Mental State Examination (MMSE); oral conditions were reflected by the number of missing index teeth, bleeding on probing, and probing pocket depth (PD). In rats: a ligature-induced (Lig) periodontitis model and Aβ25-35-induced model of Alzheimer's disease (AD) were established; tumor necrosis factor-α (TNF-α), interleukin 1 (IL-1), interleukin 6 (IL-6), and C-reactive protein levels in the hippocampus and cerebral cortex were detected., Results: MMSE scores for the number of missing index teeth ≥ 7 group were significantly lower than those in the ≤ 6 group. A negative relationship (correlation coefficient ρ = -0.310, P = 0.002) was observed between MMSE scores and number of missing index teeth. More missing index teeth and lower education levels were independent risk factors for cognitive decline. A negative relationship (correlation coefficient ρ = -0.214, P = 0.031) was observed between MMSE scores and average PD. TNF-α and IL-6 levels in the hippocampus of the Lig+AD group were significantly higher than those of the AD group. IL-1 and IL-6 levels in the cerebral cortex of the Lig+AD group were significantly higher than those of the AD group., Conclusion: Poor oral health conditions including more missing index teeth and higher average PD may be risk factors for cognitive decline. Periodontitis may increase inflammatory cytokines in rat models of AD., Competing Interests: The authors have declared that no competing interests exist.

Objective: Smoking causes pathological changes in all tissues, including gingiva and alveolar bone. The aim of present study was to evaluate apoptotic tissue alterations and tissue destruction in smoker and non-smoker periodontitis patients and healthy individuals., Methods: Gingival biopsy samples from 15 systemically and orally healthy individuals (Group 1), 15 systemically healthy periodontitis patients (Group 2), 15 systemically and orally healthy smokers (Group 3), and 15 systemically healthy smoker periodontitis patients (Group 4) were enrolled in the present study. Clinical periodontal measurements as plaque index (PI), gingival index (GI), and clinical attachment levels (CAL) were recorded, and gingival biopsies were obtained. Biopsy samples were fixed in formalin solution and embedded in paraffin. Fibroblast and inflammatory cell counts were determined via histomorphometrically. Hypoxia-inducible factor alpha (HIF-1α), vascular endothelial growth factor(VEGF), tissue inhibitor of matrix metalloproteinase-1(TIMP-1), matrix metalloproteinases-8(MMP-8) expressions, Bax, Bcl-2, and caspase-3 expressions were evaluated via immunohistochemistry., Results: Demographic data of the study groups were similar. Smoking levels of the smokers were also similar. The highest fibroblast cell counts were observed in healthy controls and the counts were similar in other groups. The highest inflammatory cell counts were found in smoker periodontitis group, and the lowest counts were found in healthy control groups. The differences were statistically significant. HIF-1α and Bax expressions were elevated and Bcl-2 decreased in smoker periodontitis patients compared with healthy individuals. However, there were no differences in VEGF, MMP-8, and TIMP-1 expressions., Conclusion: Within limits of present study, it can be suggested that both smoking and periodontitis caused similar decrease in fibroblast counts while causing a dramatic increase in inflammatory cell counts. Increased apoptosis and hypoxia also accompanied to the increased inflammation., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and objectives: Periodontitis is a multifactorial chronic inflammatory infectious disease in which an infection is necessary, but not sufficient, for development of the condition. Individual susceptibility strictly linked to the immune and inflammatory response of the organism must also be present. Low-grade inflammation (LGI) is a systemic status of chronic sub-clinical production of inflammatory factors. This condition represents a risk factor for many chronic diseases including diabetes, cardiovascular disease, cerebrovascular disease, neurodegenerative disease and cancer. This scoping review aims to clarify, summarize and disseminate current knowledge on the possible link between periodontitis, LGI and systemic health. Materials and Methods: PRISMA Extension for Scoping Reviews guidelines were followed. An ad-hoc created keyword string was used to search the electronic databases of PubMed/Medline, Embase, The Cochrane Library and ClinicalTrials.gov. A hand search of specialized journals and their reference lists was also performed. Results: 14 studies that respected eligibility criteria were selected and analyzed. There is emerging evidence of strong links between periodontitis, LGI and systemic health. On the one hand, periodontitis influences the systemic status of LGI and on the other hand, the systemic production of inflammatory factors affects periodontitis with a bidirectional connection. Conclusions: LGI and the subsequent onset of a systemic inflammatory phenotype can be considered the common substrate of many chronic inflammatory diseases including periodontitis, with multiple mutual connections between them. Understanding of the biological principles and mechanisms underlying such a complex interrelationship could lead to significant improvements in the field of personalized diagnostics and therapeutic protocols., Competing Interests: The authors declare no conflict of interest.

A morphological and immunohistochemical study of periodontal tissues was performed in patients with chronic generalized periodontitis who underwent dental implantation. We studied 44 biopsy specimens from 21 patients (13 women and 8 men) aged 35-60 years with a diagnosis of periimplantation mucositis (7 patients), periimplantitis (8 patients), and severe chronic generalized periodontitis (6 patients). It was established that periimplantitis differs from periimplantation mucositis by a more pronounced inflammatory reaction with a clear predominance of plasma cells in the infiltrate, which captures the fibrous capsule around the implant, destroys it and further spreads to the bone tissue. Based on the immunohistochemical differences in SMA, VEGF, and Ki-67, it is concluded that periimplantation mucositis and periimplantitis are successive stages of progression of the same process. When comparing chronic generalized periodontitis and periimplantitis, the latter shows much more pronounced inflammatory and destructive processes in the area of the implant, due to the addition of immune inflammation, impaired regeneration processes, and destruction of bone tissue.

The present study examined the hemodynamics [arterial pressure (AP), AP variability (APV), heart rate (HR), and heart rate variability (HRV)], cardiac function (echocardiographycally), and myocardial inflammation in Balb/c mice submitted to Periodontitis, through the ligation of the left first molar, or Sham surgical procedure. The first protocol indicated that the AP was similar (136 ± 2 vs. 132 ± 3 mmHg in Sham), while the HR was higher in mice with Periodontitis (475 ± 20 vs. 412 ± 18 bpm in Sham), compared to their Sham counterparts. The APV was higher in mice with Periodontitis when evaluated in the time domain (4.5 ± 0.3 vs. 3.4 ± 0.2 mmHg in Sham), frequency domain (power of the LF band of systolic AP), or through symbolic analysis (patterns 0V + 1V), indicating a sympathetic overactivity. The HRV was similar in the mice with Periodontitis, as compared to their Sham counterparts. In the second protocol, the mice with Periodontitis showed decreased cardiac output (10 ± 0.8 vs. 15 ± 1.4 mL/min in Sham) and ejection fraction (37 ± 3 vs. 47 ± 2% in Sham) associated with increased myocardial cytokines (Interleukin-17, Interleukin-6, and Interleukin-4). This study shows that experimental Periodontitis caused cardiac dysfunction, increased heart cytokines, and sympathetic overactivity, in line with epidemiological studies indicating an increased risk of cardiovascular events in clinical Periodontitis.

Gingivitis and periodontitis are associated with a negative impact on Oral Health Related Quality of Life (OHRQoL), exerting a significant influence on aspects related to the patients' function and esthetics. Periodontitis has been associated with several systemic conditions, including adverse pregnancy outcomes, cardiovascular diseases, type 2 diabetes mellitus (DM), respiratory disorders, fatal pneumonia in hemodialysis patients, chronic renal disease and metabolic syndrome. The aim of this paper was to review the results of different periodontal treatments and their impacts on patients' OHRQoL and systemic health. Non-surgical and surgical periodontal treatments are predictable procedures in terms of controlling infection, reducing probing pocket depth and gaining clinical attachment. In addition, the treatment of periodontitis may significantly improve OHRQoL and promote a reduction in the levels of systemic markers of inflammation, including some cytokines associated with cardiovascular diseases. Studies have also suggested that periodontal treatment may improve glycemic control in patients with DM. Strategies and actions for preventing the onset and recurrence of periodontitis, and the challenges facing the field of periodontology in the XXI century are presented in this review.

Objectives: To assess and compare dietpractices, body mass index (BMI), and oral health-related quality of life (OHRQoL) in adults with and without periodontitis., Methods: Demographics, health-related behaviors, BMI, dental and periodontal parameters, diet practices, and Oral Health Impact Profile-14 (OHIP-14) were collected from 62periodontitis patients and 100 controls without periodontitis., Results: Havingperiodontitis was positively associated with male sex ( p =0.004), older age ( p <0.001), smoking pack-years ( p = 0.006), weight ( p = 0.008), BMI ( p = 0.003), number of meals per day ( p <0.001) and had a negative associationwithdecayed teeth ( p = 0.013), alcohol ( p = 0.006), and sweets ( p = 0.007) consumption.Periodontitis patients were more likely to avoid carbonated beverages ( p = 0.028), hot ( p = 0.003), and cold drinks ( p = 0.013), cold ( p = 0.028), hardtextured ( p = 0.002), and fibrous foods ( p = 0.02) thanthe controls, and exhibited higher global OHIP-14 ( p <0.001) andmost domain scores. Age ( p <0.001), BMI ( p =0.045), number of meals per day ( p = 0.024), and global OHIP-14 score ( p <0.001) remained positivelyassociated with periodontitis in the multivariate analysis., Conclusions: Periodontitis patients exhibitedhigher BMI and altered dietpracticesand OHRQoL as compared to controls. Assessment of diet practices, BMI,and OHRQoLshould bepart of periodontal work-up. Dentists and dietitians shouldcollaborate to design strategies to addressthese challenges., Competing Interests: The authors declare no conflict of interest.

Introduction: Excessive weight is associated with periodontitis because of inflammatory mediators secreted by the adipose tissue. Periodontal impairments can occur during pregnancy due to association between high hormonal levels and inadequate oral hygiene. Moreover, periodontitis and excessive weight during pregnancy can negatively affect an infant's weight at birth., Objective: This observational, cross-sectional study aimed to evaluate the association between pre-pregnancy overweight/obesity, periodontitis during the third trimester of pregnancy, and the infants' birth weight., Methodology: The sample set was divided into 2 groups according to the preconception body mass index: obesity/overweight (G1=50) and normal weight (G2=50). Educational level, monthly household income, and systemic impairments during pregnancy were assessed. Pocket probing depth (PPD) and clinical attachment level (CAL) were obtained to analyze periodontitis. The children's birth weight was classified as low (<2.5 kg), insufficient (2.5-2.999 kg), normal (3-3.999 kg), or excessive (≥4 kg). Bivariate analysis (Mann-Whitney U test, t-test, chi-squared test) and logistic regression (stepwise backward likelihood ratio) were performed (p<0.05)., Results: G1 showed lower socioeconomic levels and higher prevalence of arterial hypertension and gestational diabetes mellitus during pregnancy than G2 (p=0.002). G1 showed higher means of PPD and CAL (p=0.041 and p=0.039, respectively) and therefore a higher prevalence of periodontitis than G2 (p=0.0003). G1 showed lower infants' birth weight than G2 (p=0.0004). Excessive maternal weight and educational levels were independent variables associated with periodontitis during the third trimester of pregnancy (X2[2]=23.21; p<0.0001). Maternal overweight/obesity was also associated with low/insufficient birth weight (X2[1]=7.01; p=0.008)., Conclusion: The present findings suggest an association between excessive pre-pregnancy weight, maternal periodontitis, and low/insufficient birth weight.

The aim of the study was to describe the oral health and orofacial function of Mexican patients with rheumatoid arthritis (RA) and their association with clinical and radiological aspects of the disease. Patients with RA received a complete odontological exam, which also included a clinical and radiographic assessment of the temporomandibular joint (TMJ). The rheumatologic assessment included detailed profiling of the disease and serological and radiographic parameters. The study included 62 RA patients; the median (min-max) age was 51 (18-72) years old and 8.5 (1-39) years of disease duration. The 63.6% of the patients had DAS28 ≥ 3.2, and a median (min-max) of Sharp/van der Heijde score (SvdHS) of 41 (0-214). 98.3% of the patients presented caries, which were severe in 53.3% of the cases. The 73.8% of the patients were missing teeth due to caries, with a median (min-max) of 4 (0-32) teeth missing per patient. Oral hygiene was classified as bad in 49.1% of patients and only 15.3% of them had a healthy periodontium. The TMJ function was abnormal in 98.4% of the patients and 62.9% of them presented moderate or severe TMJ disorder (TMD). The radiographic damage of the TMJ correlated positively with the SvdHS. No correlations were found between disease activity or structural progression and orofacial variables, including periodontitis. There are severe oral and orofacial health problems in RA patients despite having medical attention for their disease. Multidisciplinary management remains an area of opportunity for both the medical specialists and the health system in our country.

The aim of this prospective cohort study was to investigate the association between intrauterine fetal growth patterns and periodontal status in pregnant women. Fifty-three pregnant women were recruited. Periodontitis was diagnosed based on probing pocket depth and clinical attachment level. Maternal urinary 8-hydroxy-2'-deoxyguanosine levels and body mass index were recorded. Ultrasonographic measurements of the biparietal diameter (BPD), abdominal circumference (AC), and femur length (FL) were recorded, and estimated fetal weight (EFW) was calculated. In addition, approximation spline curves of BPD, AC, FL, and EFW were obtained throughout the gestation period. Recorded delivery outcomes were gestational age (GA), birth weight and length, sex, placental weight, and umbilical cord length. Forty-four participants (34.1 ± 4.9 years) were analyzed. Mean neonatal birth weight was 2906.0 ± 544.4 g. On multiple regression analysis, birth weight was related with periodontitis (standardized β = -0.21, P = 0.001). For EFW and BPD, the curves of the periodontitis group were located lower than those of the non-periodontitis group, with significant differences after 32 weeks and 20 weeks of GA, respectively. In conclusion, periodontal treatment before conception may be recommended and a good periodontal condition in the early stage of pregnancy at the latest is desirable for infant growth.

The main advantages of studying the pathophysiology of periodontal disease utilizing murine models are the reduced cost of animals, array of genetically modified strains, the vast number of analyses that can be performed on harvested soft and hard tissues. However, many of these systems are subject to procedural criticisms. As an alternative, the ligature-induced model of periodontal disease, driven by the localized development and retention of a dysbiotic oral microbiome, can be employed, which is rapidly induced and relatively reliable. Unfortunately, the variants of ligature-induced murine periodontitis protocol are isolated to focal regions of the periodontium and subject to premature avulsion of the installed ligature. This minimizes the amount of tissue available for subsequent analyses and increases the number of animals required for study. This protocol describes the precise manipulations required to place extended molar ligatures with improved retention and usage of a novel rinse technique to recover oral neutrophils in mice with an alternative approach that mitigates the aforementioned technical challenges.

Objective: The evidence is inconclusive regarding the effect of periodontal treatment on glycemic control and systemic inflammation in patients with type 2 diabetes (T2D) and periodontitis. To evaluate the effect of scaling and root planing (SRP) on the metabolic control and systemic inflammation of patients with type 2 diabetes (T2D)., Methodology: A literature search was conducted using the MEDLINE database via PubMed and the Cochrane Central Register of Controlled Trials, from their oldest records up to July 2018. Only randomized clinical trials (RCT) were considered eligible for evaluating the effect of periodontal treatment on markers of metabolic control [glycated hemoglobin (HbA1C)] and systemic inflammation [C-reactive protein (CRP)] in patients with T2D. The quality of the studies was evaluated using the Cochrane Collaboration risk assessment tool. Meta-analyses were performed for HbA1c and CRP using random effects models. The size of the overall intervention effect was estimated by calculating the weighted average of the differences in means (DM) between the groups in each study. Heterogeneity was assessed using the Q-statistic method (x2 and I²). The level of significance was established at p<0.05., Results: Nine RCT were included. SRP was effective in reducing HbA1c [DM=0.56 (0.36-0.75); p<0.01] and CRP [DM=1.89 (1.70-2.08); p<0.01]. No heterogeneity was detected (I2=0%, p>0.05)., Conclusions: SRP has an impact on metabolic control and reduction of systemic inflammation of patients with T2D.

This study evaluated the effects of replacing a saturated fat diet by n-3 polyunsaturated fatty acids (n-3PUFA), on alveolar bone loss in hypercholesterolemic rats with experimental periodontitis (PD)., Methods: Eight week old Wistar rats were assigned according to dietary intake. Control group (C, n = 15) fed a commercial diet throughout the experiment. Atherogenic group (AT, n = 30) fed AT diet for 3 weeks; thereafter, AT was randomized to receive either a n-3PUFA (n = 15) or to continue with AT (n = 15) diet. Subsequently, PD was induced in all groups by unilateral ligature (L) of the first molar (M1) of the left mandible, non-ligated contralateral molars served as controls. After every week of PD induction, 5 rats per group were euthanized. Serum was collected for lipids assays and hemi-mandibles were subjected to histomorphometric (% upper and lower interradicular bone volume and periodontal ligament height, hPDL) and radiographic analyses (periodontal bone support, PBS, in ligated teeth, between M1-M2)., Results: Rats fed n-3PUFA diet rapidly induced a significant reduction in the serum lipids (p < 0.001). In all rats the ligated teeth showed a greater bone loss as compared with the unligated molars. At the end of the experiment the AT + L was the worst in % lower bone volume (p < 0.01), hPDL and PBS (p < 0.05). In contrast, rats fed n-3PUFA + L was similar to those rats fed C diet (p > 0.05)., Conclusion: Alveolar bone and dyslipidemia improved by substituting saturated fat intake for a n-3PUFA rich diet, in hypercholesterolemic rats with PD., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Periodontitis is an inflammatory disease caused by pathogenic oral microorganisms that induce the destruction of periodontal tissue. We sought to identify the relevant differentially expressed genes (DEGs) and clarify the mechanism underlying the rapid alveolar bone loss by using ligature-induced periodontitis in mice. A silk ligature was tied around the maxillary left second molar in 9-week-old C57BL/6 J male mice. In-vivo micro-CT analysis revealed that ligation induced severe bone loss. RNA-sequencing analysis, to examine host responses at 3 days post-ligation, detected 12,853 genes with fragments per kilobase of exon per million mapped reads ≥ 1, and 78 DEGs. Gene ontology term enrichment analysis revealed the expression profiles related to neutrophil chemotaxis and inflammatory responses were significantly enriched in the ligated gingiva. The expression levels of innate immune response-related genes, including S100a8 and S100a9, were significantly higher in the ligated side. S100A8 was strongly detected by immunohistochemistry at the attached epithelium in ligated sites. Inhibition of S100A8 and S100A9 expression revealed that they regulated IL1B and CTSK expression in Ca9-22 cells. Thus, innate immune response-related molecules might be associated with the burst-destruction of periodontal tissue in ligature-induced periodontitis. Especially, S100A8 and S100A9 may play an important role in alveolar bone resorption.

The ligand of the receptor activator of NF- κ B (RANKL) is a key molecule in the formation of osteoclasts, the key cells that cause the disease-associated alveolar bone resorption in periodontitis. We hypothesized that polymorphonuclear leukocytes (PMNs), found as the most prominent cells of inflamed periodontal tissues, could play an important role in providing signals to trigger osteoclastogenesis and thus activating pathological bone resorption in periodontitis. RANKL expression was investigated on circulatory PMNs (cPMNs) and oral PMNs (oPMNs) taken from both controls and periodontitis patients. On average, 2.3% and 2.4% RANKL expression was detected on the cPMNs and oPMNs from periodontitis patients, which did not differ significantly from healthy controls. Since cPMNs may acquire a more osteoclastogenesis-facilitating phenotype while migrating into the inflamed periodontium, we next investigated whether stimulated (with LPS, TNF- α , or IL-6) cPMNs have the capacity to contribute to osteoclastogenesis. Enduring surface expression of RANKL for short-lived cells as cPMNs was achieved by fixating stimulated cPMNs. RANKL expression on stimulated cPMNs, as assessed by flow cytometry and immunohistochemistry, was limited (6.48 ± 0.72%, mean expression ± SEM) after 24 and 48 hours of stimulation with LPS. Likewise, stimulation with TNF- α and IL-6 resulted in limited RANKL expression levels. These limited levels of expression did not induce osteoclastogenesis when cocultured with preosteoclasts for 10 days. We report that, under the aforementioned experimental conditions, neither cPMNs nor oPMNs directly induced osteoclastogenesis. Further elucidation of the key cellular players and immune mediators that stimulate alveolar bone resorption in periodontitis will help to unravel its pathogenesis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 Carolyn G. J. Moonen et al.)

This study investigated whether periodontitis affects systemic bone status and whether FRAX® is a screening tool for periodontal disease in elderly women. The findings showed that bone density was not influenced by periodontitis and highlighted that women with FRAX® score above the intervention threshold had greater chance to present severe periodontitis., Purpose: This study investigated whether periodontal disease is a predictor for systemic bone loss among elderly women. The utilization of FRAX® as a screening tool for severe periodontitis was also evaluated in this population., Methods: Current bone mineral density (BMD) for lumbar spine and proximal femur was used as an indicator of "bone status." Number of interdental sites with severe clinical attachment loss, frequency of bleeding on probing, and percentage of tooth loss due to periodontitis represented "periodontal disease" that was tested as a predictor of bone loss in a structural equation modeling analysis involving 110 participants. The intake of antiosteoporosis medication was considered in the analysis. Four other different criteria for periodontitis classification were also tested. FRAX® for major fracture was calculated without BMD, and with intervention threshold set by age. Longitudinally, BMD changes up to 10 years were also obtained and checked for possible association with periodontitis., Results: Periodontal disease was not a predictor for worse systemic bone status according to the different periodontal disease classifications, and was not associated with BMD changes. Antiosteoporosis medication directly predicted periodontal disease and systemic bone status. Women with FRAX® score above the intervention threshold had higher chance for periodontitis in more advanced stages: III/IV (OR = 1.13, 95% CI [1.04 to 1.22], p = 0.03)., Conclusion: Periodontal disease did not constitute a predictor for reduced systemic bone density in the studied population of elderly women. On the other hand, FRAX® demonstrated to be a useful tool to suggest periodontal evaluation. Antiresorptive medication showed benefits on periodontal and bone status.

Periodontitis is a common intraoral infection and is inextricably linked to systemic diseases. Recently, the regulation between host immunologic response and periodontal pathogens has become a hotspot to explain the mechanism of periodontitis and related systemic diseases. Since Porphyromonas gingivalis ( P. gingivalis ) was proved as critical periodontal pathogen above all, researches focusing on the mechanism of its virulence factors have received extensive attention. Studies have shown that in the development of periodontitis, in addition to the direct release of virulent factors by periodontal pathogens to destroy periodontal tissues, over-low or over-high intrinsic immune and inflammatory response mediated by Toll-like receptors (TLRs) can lead to more lasting destruction of periodontal tissues. It is very necessary to sort out how various cytopathic factors of P. gingivalis mediate inflammation and immune responses between the host through TLRs so as to help precisely prevent, diagnose, and treat periodontitis in clinic. This review summarizes the role of three most widely studied pathogenic factors produced by P. gingivalis (lipopolysaccharide, gingipains, pili) and their interactions with TLRs at the cellular and molecular level in the progress of periodontitis.

Growing evidence suggests close associations between periodontitis and atherosclerosis. To further understand the pathological relationships of these associations, we developed periodontitis with ligature placement around maxillary molars or ligature placement in conjunction with Porphyromonas gingivalis lipopolysaccharide injection at the ligature sites (ligature/P.g. LPS) in Apolipoprotein E knock out mice and studied the atherogenesis process in these animals. The mice were fed with high fat diet for 11 weeks and sacrificed for analyzing periodontitis, systemic inflammation, and atherosclerosis. Controls did not develop periodontitis or systemic inflammation and had minimal lipid deposition in the aortas, but mice receiving ligature or ligature/P.g. LPS showed severe periodontitis, systemic inflammation, and aortic plaque formation. The aortic plaque contained abundant macrophages and cells expressing both endothelial and mesenchymal cell markers. The severity of periodontitis was slightly higher in mice receiving ligature/P.g. LPS than ligature alone, and the magnitude of systemic inflammation and aortic plaque formation were also notably greater in the mice with ligature/P.g. LPS. These observations indicate that the development of atherosclerosis is due to systemic inflammation caused by severe periodontitis. In vitro, P.g. LPS enhanced the secretion of pro-inflammatory cytokines from macrophages and increased the adhesion of monocytes to endothelial cells by upregulating the expression of adhesion molecules from endothelial cells. Moreover, secretory proteins, such as TNF-α, from macrophages induced endothelial-mesenchymal transitions of the endothelial cells. Taken together, systemic inflammation induced by severe periodontitis might exacerbate atherosclerosis via, in part, causing aberrant functions of vascular endothelial cells and the activation of macrophages in mice.

Periodontal ligament stem cells (PDLSCs) can repair alveolar bone defects in periodontitis in a microenvironment context-dependent manner. This study aimed to determine whether different extracellular matrices (ECMs) exert diverse effects on osteogenic differentiation of PDLSCs and accurately control alveolar bone defect repair. Methods : The characteristics of PDLSCs and bone marrow mesenchymal stem cells (BMSCs) with respect to surface markers and multi-differentiation ability were determined. Then, we prepared periodontal ligament cells (PDLCs)-derived and bone marrow cells (BMCs)-derived ECMs (P-ECM and B-ECM) and the related decellularized ECMs (dECMs). Transmission electron microscopy (TEM), scanning electron microscopy (SEM), atomic force microscopy (AFM), and protein mass spectrometry were used to distinguish the ECMs. The expression of Type IV collagen A2 (COL4A2) in the ECMs was inhibited by siRNA or activated by lentiviral transduction of relevant cells. The stemness, proliferation, and differentiation of PDLSCs were determined in vitro in different dECMs. For the in vivo analysis, different dECMs under the regulation of COL4A2 mixed with PDLSCs and Bio-Oss bone powder were subcutaneously implanted into immunocompromised mice or in defects in rat alveolar bone. The repair effects were identified by histological or immunohistochemical staining and micro-CT. Results : B-dECM exhibited more compact fibers than P-dECM, as revealed by TEM, SEM, and AFM. Protein mass spectrometry showed that COL4A2 was significantly increased in B-dECM compared with P-dECM. PDLSCs displayed stronger proliferation, stemness, and osteogenic differentiation ability when cultured on B-dECM than P-dECM. Interestingly, B-dECM enhanced the osteogenic differentiation of PDLSCs to a greater extent than P-dECM both in vitro and in vivo, whereas downregulation of COL4A2 in B-dECM showed the opposite results. Furthermore, the classical Wnt/β-catenin pathway was found to play an important role in the negative regulation of osteogenesis through COL4A2, confirmed by experiments with the Wnt inhibitor DKK-1 and the Wnt activator Wnt3a. Conclusion : These findings indicate that COL4A2 in the ECM promotes osteogenic differentiation of PDLSCs through negative regulation of the Wnt/β-catenin pathway, which can be used as a potential therapeutic strategy to repair bone defects., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

This investigation compared the microbiomes colonizing teeth during the initiation, progression, and resolution of periodontitis in nonhuman primates ( Macaca mulatta ) at different ages. Subgingival plaque samples were collected at baseline; 0.5, 1, and 3 months following ligature-induced periodontitis; and following naturally occurring disease resolution at 5 months. Samples were analyzed using 16S amplicon sequencing to identify bacterial profiles across age groups: young (<3 years of age), adolescent (3 to 7 years), adult (12 to 15 years), and aged (17 to 23 years). α-Diversity of the microbiomes was greater in the adult/aged samples than in the young/adolescent samples. β-Diversity of the samples demonstrated clear age group differences, albeit individual variation in microbiomes between animals within the age categories was noted. Phylum distributions differed between the young/adolescent animals and the adult/aged animals at each of the time points, showing an enrichment of the phyla Spirochetes , Fusobacteria , and Bacteroidetes associated with periodontitis. Major differences in the top 50 operational taxonomic units (OTUs) were noted in the young and adolescent microbiomes during initiation and progression postligation compared to the adult and aged animals. The proportions of a large number of species in the top 50 OTUs were lower at baseline and in resolved disease microbiomes in the young samples, while profiles in adolescent animals were more consistent with the disease microbiomes. Microbiome profiles for resolution for adults and aged animals appeared more resilient and generally maintained a pattern similar to that of disease. Use of the model can expand our understanding of the crucial interactions of the oral microbiome and host responses in periodontitis., (Copyright © 2019 American Society for Microbiology.)

Objective: To evaluate the effect of periodontitis (PD) on glucoregulatory hormones in obesity, never explored so far, a cross-sectional study was conducted in 110 severely obese, non-diabetic individuals., Methods: We collected clinical periodontal parameters, including probing pocket depth (PPD), bleeding on probing (BOP), clinical attachment level (CAL). Insulin, glucagon, GLP-1 and GIP were measured after 3 days of standardized diet., Results: Forty-seven subjects had periodontitis (PD+) and 63 did not (PD-). PD+ showed 30.3% of gingival sites with PPD > 4 mm, 55.2% of BOP sites and a mean CAL loss of 4.1 mm. Compared with PD-, PD+ had higher glucagon (26.60 [25.22] vs 3.93 [7.50] ng/l, p < 0.0001) and GIP levels (10.56 [13.30] vs 6.43 [8.43] pmol/l, p < 0.001), while GLP-1 was reduced (11.78 [10.07] vs 23.34 [16.80] pmol/l, p < 0.0001). Insulin did not differ. In PD+, after adjustment for confounders, PPD was positively related to glucagon (β = 0.424, p = 0.002) and inversely to GLP-1 (β = -0.159, p = 0.044)., Conclusions: We describe for the first time an impaired incretin axis coupled with a relative hyperglucagonemia in obese non-diabetic individuals with PD, that might contribute to deteriorate their glucose tolerance and partially explain the higher risk of diabetes observed in these patients.

Smoking is a leading cause of preventable death. The effect of tobacco is even more contundent in people with mental illness and, in general, cigarette smoking addiction is influenced by genetic factors. The opioid system is involved in the mesolimbic reward system, which is of great importance in addictive behaviors, such as smoking and is influenced by genes such as the OPRM1. The aim of this study was to evaluate if selecting a comparison group that include light smokers versus people that never smoked impacts the results of genetic association studies. In addition, to evaluate the genetic association in different groups of smokers by analyzing independent covariates such as mental illness and clinical dental data. All subjects were participants of the Dental Registry and DNA Repository project. Genotyping was carried out using TaqMan chemistry for two markers in OPRM1 (rs553202 and rs7755635). Logistic regression analyses were performed as implemented in PLINK. The established value for alpha was 5%, and the Hardy-Weinberg equilibrium was evaluated by the chi-square test with one degree of freedom for each marker. 1,897 patients were included, which were allocated to eight distinct groups, according to the frequency and quantity of cigarettes smoked and mental illness status. There was no significant association between the two markers in OPRM1 and smoking. When mental illness and dental clinical data (tooth loss, dental caries, and periodontitis) were used as covariates, there were associations between heavy smoking and OPRM1, when non-smokers were used as comparison. We did not have diet or microbiome data to consider for these dental analyses and suggest that these kinds of data should be always incorporated in the future. Significant results were found only when the covariables mental illness and oral clinical data were added to the analysis., Competing Interests: The authors have declared that no competing interests exist.

Objective: To describe the methodological aspects of a Prospective Cohort Study of adult oral health in Piracicaba, Brazil., Results: This Prospective Cohort Study evaluated adults (20-64 years old) between the years of 2011 and 2015, in Piracicaba, São Paulo, Brazil. The main objective was to evaluate the risk factors for tooth loss in adults. Data were collected at households and selected via probabilistic sampling, through clinical examination of caries, considering as variables the decayed, missing and filled permanent teeth index, need for caries treatment, periodontal disease (Community Periodontal Index and Periodontal Attachment Loss), use and need for dental prosthesis, and presence of visible biofilm. A questionnaire about demographic, socioeconomic and health habits, use of dental services, self-perceived quality of life (Oral Health Impact Profile-14) and health literacy (14-item Health Literacy Scale) was also employed. In 2011, 248 adults participated, and in 2015, 143 (follow-up rate = 57.7%). Despite the follow-up sample loss, most sociodemographic characteristics remained in the participant sample: for example, women (72.0%) (p = 0.534), family income between R$545,00 and R$1090,00 (63.9%) (p = 0.920), above 11 years of education (53.1%) (p = 0.200) and belonging to middle class (67.1%) (p = 0.909).

Both periodontitis and chronic obstructive pulmonary disease (COPD) are among the most common diseases associated with smoking. These conditions frequently present alongside comorbidities including diabetes, coronary heart disease, duodenal ulcer, deep vein thrombosis, pulmonary embolism, osteoporosis and muscle atrophy. Chronic inflammation contributes to the pathology of both periodontitis and COPD, and in patients suffering from both conditions treatment of periodontitis may lead to relief from COPD symptoms as well. Smoking contributes to the underlying pathophysiology by causing local inflammation, increasing the production of proinflammatory cytokines and most importantly, by locally increasing the activity of proteolytic enzymes which degrade the extracellular matrix in both periodontal and lung interstitial tissue. The increase in protease activity and extracellular matrix degradation may explain why periodontitis and COPD comorbidity is so common, a finding which also indicates that therapeutic interventions targeting protease activity and the inflammatory response may be beneficial for both conditions.