Inflammasome initiates inflammation via the maturation of interleukin-1 beta (IL-1β). Periodontitis is a prevalent, male-biased disease characterized by inflammation-driven bone loss, yet the mechanism(s) of this sex bias is unknown. This study explored whether enhanced inflammasome represents a causal mechanism for this bias. Analyses of three separate human studies (>6,200 samples) show that males have significantly higher IL-1β in the gingival crevicular fluid than females during health and periodontitis. This pattern is experimentally reproduced with different versions of the ligature-induced periodontitis mouse model where males show greater IL-1β secretion than females. The inflammasome drives bone resorption in males but not females as revealed by analyses of inflammasome gene-deletion mice. Pharmacologic treatment with a caspase-1/4 inhibitor reduces inflammatory cell infiltration, dampens osteoclastogenesis signaling (via the receptor activator of nuclear factor-kappa B pathway), and prevents bone resorption in males but not females during experimental periodontitis. While ovariectomized females show no change in their nonresponsiveness to caspase-1/4 inhibition, orchiectomized males no longer respond to the inhibition, suggesting the importance of an intact male reproductive system in the mediation of this inhibition. Thus, our study identifies inflammasome activation as causal for male-biased experimental periodontitis and supports sex-stratified studies to foster future advancement of inflammasome therapeutics in periodontics.

BACKGROUND:Peri-implantitis, an inflammatory condition occurring in the supportive tissues, is triggered by a dysbiotic biofilm that grows on implant and/or abutment surfaces. Consequently, the entire surface becomes a notorious culprit, fostering bacterial adhesion that might lead to progressive loss of supporting bone. To combat peri-implantitis, research groups worldwide have diligently pursued the development of new antimicrobial coatings. However, for the successful development of coating materials, it is crucial to clarify their intended function. In this review, we propose a clear classification of coating strategies aimed at either preventing or treating peri-implantitis. METHODS:We first delve deep within the concepts of prevention and treatment, as well as the physicochemical properties and biological requirements of each dental implant component for interacting with host tissue cells, to unravel and guide materials and technique complexity according to each purpose. RESULTS:From a preventive standpoint, the goal is to impede disease initiation. This requires coating materials that can withstand the hostile oral environment indefinitely. In the treatment category, where the disease is already established, the coating material should act directly at the infected site. Furthermore, the physicochemical properties of the new antimicrobial coating must respect the properties required by each part of the implant to not compromise the interaction of the bone-biomaterial and soft tissue-biomaterial interfaces. CONCLUSION:Despite considerable efforts in designing antimicrobial coatings, commercial success has remained elusive thus far. This underscores the need to consider essential components to facilitate the construction, validation, and eventual clinical potential of antimicrobial coatings for future marketing. PLAIN LANGUAGE SUMMARY:In this review, we have raised an essential point about the importance of considering both biological and chemical challenges in the development of antimicrobial coatings for preventing and treating peri-implantitis. From a preventive perspective, these coatings need to be designed to withstand the complex environment of the oral cavity while maintaining their integrity and functionality. This requires coatings that can resist changes in environmental factors. Conversely, in the treatment category, material coatings need to be responsive to either internal or external stimuli to activate the release of therapeutic agents. These coatings must be capable of switching on or off depending on the intensity of stimuli, allowing for targeted drug delivery to combat infection or inflammation.

BACKGROUND:Bisphosphonates (BPs) are effective in managing bone diseases due to their anti-resorptive properties but are linked to medication-related osteonecrosis of the jaw (MRONJ), particularly concerning dental implants. This study explored the combined impact of ligature-induced peri-implant inflammation and zoledronic acid (ZA), a BP, using a murine model. METHODS:Twenty-four mice underwent bilateral maxillary molar extractions and implant placements, with ZA or vehicle treatment and ligature placement on the left side. Two groups were defined: group 1 (vehicle-treated) with control (Veh-C) and ligature (Veh-L) implants, and group 2 (ZA-treated) with control (ZA-C) and ligature (ZA-L) implants. Clinical, micro-CT, histological, and immunohistochemical analyses were performed. We hypothesized that peri-implant inflammation elevates MRONJ risk with BP treatment. RESULTS:Ligature groups showed increased soft tissue edema compared to controls, without differences between vehicle and ZA treatments. The Veh-L group exhibited significantly greater bone loss than other groups. Histology showed higher inflammatory infiltrate in ligature groups. Osteocyte empty lacunae and osteonecrosis were significantly greater in ZA-L. Picrosirius red staining revealed disorganized collagen fibers and separation in ZA-L. Immunohistochemistry showed increased neutrophils (NIMP-R14+) and monocytes/macrophages (CD11b+) in the ligature groups, with no significant differences between Veh-C and ZA-C. CONCLUSION:Ligature treatment enhances peri-implant inflammation, with ZA heightening the risk of MRONJ. These findings highlight the critical importance of early detection and management of peri-implant inflammation in patients undergoing BP therapy, particularly those at high risk of MRONJ. Clinicians should emphasize preventive measures, such as regular monitoring of peri-implant health and reducing local inflammatory triggers, to mitigate the adverse effects of BPs on peri-implant bone health. PLAIN LANGUAGE SUMMARY:Dental implants are a reliable solution to replace missing teeth. However, like natural teeth, implants can develop inflammation around them-peri-implantitis. Our study found that, when this inflammation occurs in patients taking BPs (a medication commonly used to treat osteoporosis and other bone diseases), the risk of developing a serious jaw condition called osteonecrosis (ONJ) increases significantly. ONJ prevents the jawbone from healing properly, leading to pain, infection, and even exposed bone. These findings highlight the importance of preventing and managing inflammation around dental implants to reduce the risk of complications, especially in patients taking BPs. Our research suggests regular dental check-ups and proper oral hygiene can help maintain implant health and prevent severe bone-related conditions. Patients and healthcare providers can take proactive steps to improve long-term oral health outcomes by understanding these risks.

Peri-implantitis (PI) is an inflammatory disease that affects supportive tissues around dental implants, and its progression eventually leads to bone loss and implant failure. However, PI effects may be different based on the presence or absence of adjacent teeth. The objective was to investigate the differences in bone loss and inflammation between implants placed adjacent to a tooth or edentulous area in a ligature-induced PI model. Materials and methods include the following: Three-week-old C57BL/6J male mice underwent maxillary first (AT; n = 12) or first and second (AE; n = 8) left molar extractions. In both groups, implants were placed in the first molar region 8 weeks after tooth extraction. Each group was further divided into control (C) or ligature (PI) 4 weeks after osseointegration. The mice were euthanized 12-14 days after ligature placement. The samples were analyzed using micro-computed tomography and histology. Statistical analysis was performed using analysis of variance and Tukey multiple comparison test (P < .05). Radiographic linear analysis revealed no statistically significant differences in bone levels between the two C and PI groups. Linear bone loss was significantly greater in the PI group than in the C group. Volumetric analysis yielded similar results. Histologically, hematoxylin and eosin staining revealed no notable differences between the two C and PI groups. The PI groups showed increased levels of inflammatory infiltrates and bone resorption. Qualitative assessment of collagen through picrosirius red staining demonstrated increased collagen disorganization in the PI group compared with that in the C group. No notable differences were observed between the AT and AE groups. The presence or absence of an adjacent tooth does not influence PI-induced soft and hard tissue alterations.

The aim of this study was to investigate the effect of thermogenic supplementation on the bone tissue of rats subjected to orthodontic movement. A total of 38 male Wistar rats underwent orthodontic movement of the left permanent maxillary first molars for 21 days. The rats were assigned to three groups: Control group: water; Thermogenic 1: C4 Beta Pump thermogenic; or Thermogenic 2: PRE-HD/Pre-workout. Micro-computed tomography (micro-CT) was used to investigate the dynamic changes in the microstructure of alveolar bone during orthodontic tooth movement in rats. Histopathologic analysis was performed by hematoxylin and eosin (H&E) staining, whereas tartrate-resistant acid phosphatase (TRAP) was employed for osteoclast count. Maxillary tissue was collected and evaluated by immunohistochemistry for receptor activator of NF-kappa B (RANK), receptor activator of NF-kappa B ligand (RANKL), and osteoprotegerin (OPG). The Thermogenic 2 group exhibited a significantly lower percentage of bone volume fraction (BV/TV) (68.21% +/- 17.70%) compared to the control (86.84% + 12.91%) and Thermogenic 1 groups (86.84% + 15.94%) (p < 0.05). The control group had a significantly higher mean orthodontic movement in the mesial direction (0.2143 mm + 0.1513 mm) than the Thermogenic 2 group (0.0420 mm + 0.05215 mm) (p < 0.05). The Thermogenic 2 and Thermogenic 1 groups showed a stronger immunostaining for RANKL when compared to the control group (p < 0.05). The supplementation used in the Thermogenic 2 group (PRE-HD/Pre-workout) induced alveolar bone loss in rats subjected to orthodontic movement, which can be related to the regulation of the RANK/RANKL/OPG signaling pathway. This suggests the influence of thermogenic supplements on bone metabolism seems to depend on their composition.

IntroductionCaffeine is a widely consumed substance with several effects on bone metabolism. This study aimed to investigate the effect of caffeine on the bone tissue of rats submitted to orthodontic movement.MethodsTwenty-five male Wistar rats underwent orthodontic movement (21 days) of the first permanent maxillary molars on the left side. The experimental group (caffeine; n = 13) and control group (n = 12) received caffeine and water, respectively, by gavage. Microcomputed tomography was performed to analyze orthodontic movement. Histologic analysis of the inflammatory infiltrate and osteoclast count by tartrate-resistant acid phosphatase were conducted. Maxilla tissue was evaluated for receptor activator of nuclear factor ҡB (RANK), RANK ligand (RANKL), and osteoprotegerin by immunohistochemistry.ResultsCaffeine exhibited a lower bone volume/tissue volume ratio (78.09% ± 5.83%) than the control (86.84% ± 4.89%; P <0.05). Inflammatory infiltrate was increased in the caffeine group compared with the control group (P <0.05). A higher number of tartrate-resistant acid phosphatase-positive cells was observed in the caffeine (9.67 ± 1.73) than in the control group (2.66 ± 0.76; P <0.01). Immunoexpression of RANK and RANKL in the caffeine group was greater than the control (P <0.05).ConclusionsThe use of caffeine thermogenic induces alveolar bone loss in rats submitted to orthodontic movement via activation of RANK, RANKL, and osteoprotegerin signaling pathways.

This study aimed to analyze the physical features and effect of hydroxyapatite (HAp) and Niobium/HAp CaNb2O6/Ca-3(PO4)(2) composite on critical size defect in rat calvaria. Biomaterials were characterized by X-ray diffraction (XRD), X-ray fluorescence (XRF), Particle size distribution (PSD) and Scanning Electron Microscopy (SEM). Critical size (8 mm) calvarial defects were created in Wistar rats (n = 24) distributed in three groups (90 days): Control group (CG): critical defect no treatment; HAp group: Hydroxyapatite; CNb/CPO group: CaNb2O6/Ca3(PO4)2 composite. After 90 days, calvaria samples were subjected to histological, and immunohistochemical reactions for osteopontin and osteocalcin, and Micro-CT analyses. XRD analysis confirmed the formation of a crystalline structure of CNb/CPO. XRF measurements confirmed the presence of Nb added in the sample CNb/CPO. Fracture toughness from CNb/CPO composite was 0.82 MPa.m1/2. Micro- CT showed increased trabecular number (p<0.001), decreased porosities (%) (p <0.001) and decreased trabecular separation (mm) (p<0.001) in the CNb/CPO compared to CG group. In CNb/CPO group showed presence of new bone in which connective tissue differentiates to form or indicate a bone matrix score 3 (3- 3.75, p<0.05) and strong imm unoexpression of osteopontin (p<0.05). The findings indicate that CNb/CPO showed resistance to the propagation of cracks and stimulated bone formation in calvaria defects in rats.

BACKGROUND:Medication related osteonecrosis of the jaws (MRONJ), a rare side-effect of antiresorptive medications, is described as exposed bone in the oral cavity that lasts for at least 8 weeks. Most studies report a female predilection for MRONJ; these findings could be due to the increased use of antiresorptives in females, or due to inherent differences between male versus female patients. PURPOSE:The purpose of this study was to measure and compare the incidence and severity of osteonecrosis of the jaws (ONJ) between male and female mice. STUDY DESIGN, SETTING, SAMPLE:We designed a randomized in-vivo animal study utilizing male and female mice treated with zoledronic acid (ZA). Experimental periodontitis was induced in 24 male and 24 female mice using a silk ligature following administration of saline or a potent bisphosphonate. After 8 weeks, animals were evaluated radiographically and histologically. INDEPENDENT VARIABLE:The independent variables were sex (male vs female) and treatment group (ZA vs saline control). Treatment was randomly assigned with balanced distribution between male and female animals. MAIN OUTCOME VARIABLE:The main outcome variable was ONJ status coded as present or absent. ONJ was defined as present if there was histologic contact between the ligature and the alveolar bone. Secondary outcomes of interest were radiographic and histologic parameters. ANALYSIS:Statistical differences were analyzed using a two-way analysis of variance with Tukey's post hoc test using a P value of 0.05 for significance. RESULTS:The final sample was composed of 24 vehicle treated and 24 ZA treated animals. In vehicle treated animals, 8% of female and 8% of male animals developed ONJ. In ZA treated animals, 83% of female and 92% of male animals developed ONJ. Sex was not associated with the risk (measured as incidence of disease) for developing ONJ or in the radiographic or histologic parameters that were assessed (P values >.1). CONCLUSIONS:Sex does not appear to affect the incidence of MRONJ or the severity of the disease as assessed by the radiographic and histologic parameters.

AIM:To investigate the influence of diabetes mellitus (DM) in a murine model of peri-implantitis (PI). MATERIALS AND METHODS:Twenty-seven 4-week-old C57BL/6J male mice had their first and second maxillary left molars extracted. Eight weeks later, one machined implant was placed in each mouse. Four weeks after osseointegration, the mice were divided into three groups: (a) control (C), (b) PI and (c) DM + PI. DM was induced by streptozotocin (STZ) administration. After DM induction, PI was induced using ligatures for 2 weeks. The hemimaxillae were collected for micro-CT and histological analyses. The primary outcomes consisted of linear (mm) and volumetric (mm3) bone loss. Secondary outcomes were based on histological analysis and included inflammatory infiltrate, osteoclastic activity, matrix organization, composition and remodelling. Data are presented as means ± SEM. Statistical analyses were performed using one-way ANOVA, followed by Tukey's test. RESULTS:Gingival tissue oedema was detected in the PI and DM + PI groups. Micro-CT showed significantly increased linear and volumetric bone loss in the DM + PI group compared to the C and PI groups. H&E staining showed greater inflammatory response and bone resorption in the PI and DM + PI groups than in the C group. The DM + PI group had significantly higher osteoclast numbers than the C and PI groups. Picrosirius red stained less for types I and III collagen in the PI and DM + PI groups than in the C group. There was a significant increase in monocyte/macrophage (CD-11b) counts and matrix metalloproteinases (MMP-2 and MMP-8) marker levels and a significant decrease in the matrix metalloproteinases inhibition marker (TIMP-2) levels in the DM + PI group compared to the C and PI groups. CONCLUSIONS:DM exacerbates PI-induced soft-tissue inflammation, matrix degradation and bone loss.

Considering the lack of consensus related to the impact of selective IL-6 receptor inhibition on bone remodeling and the scarcity of reports, especially on large bone defects, this study proposed to evaluate the biological impact of the selective inhibitor of interleukin-6 receptor (tocilizumab) in an experimental model of critical calvarial defect in rats. In this preclinical and in vivo study, 24 male Wistar rats were randomly divided into two groups (n=12/group): defect treated with collagen sponge (CG) and defect treated with collagen sponge associated with 2 mg/kg tocilizumab (TCZ). The defect in the parietal bone was created using an 8-mm diameter trephine drill. After 90 days, the animals were euthanized, and tissue samples (skull caps) were evaluated through micro-CT, histological, immunohistochemistry, cytokines, and RT-qPCR analyses. Tocilizumab reduced mononuclear inflammatory infiltration (P<0.05) and tumor necrosis factor (TNF)-α levels (P<0.01) and down-regulated tissue gene expression of BMP-2 (P<0.001), RUNX-2 (P<0.05), and interleukin (IL)-6 (P<0.05). Moreover, it promoted a stronger immunostaining of cathepsin and RANKL (P<0.05). Micro-CT and histological analyses revealed no impact on general bone formation (P>0.05). The bone cells (osteoblasts, osteoclasts, and osteocytes) in the defect area were similar in both groups (P>0.05). Tocilizumab reduced inflammatory cytokines, decreased osteogenic protein, and increased proteases in a critical bone defect in rats. Ninety days after the local application of tocilizumab in the cranial defect, we did not find a significant formation of bone tissue compared with a collagen sponge.

Dental implants are increasing in prevalence as desirable options for replacing missing teeth. Unfortunately, implants come with complications, and animal models are crucial to studying the pathophysiology of complications. Current murine model experiments can be lengthy, with 8 weeks of extraction socket healing before implant placement. Therefore, we aimed to investigate the efficacy of decreasing extraction healing time from 8 to 4 weeks in a dental implant mouse model. Thirty-one 3-week-old C57BL/6J male mice underwent maxillary first and second molar extractions followed by 8 (control) or 4 (test) weeks of extraction socket healing before implant placement. Mice were euthanized after 4 weeks of implant osseointegration. Samples were analyzed via microcomputerized tomography and histology. When mice received implants 4 weeks after extractions, there was no statistical difference in initial bone crest remodeling or surrounding bone volume compared to those after 8 weeks of healing. Histologically, the hard and soft tissues surrounding both groups of implants displayed similar alveolar bone levels, inflammatory infiltrate, osteoclast count, and collagen organization. A 4-week extraction healing period can be utilized without concern for osseointegration in a murine implant model and is a viable experimental alternative to the previous eight weeks of healing. While small animal implant models are less directly applicable to humans, advancements in experimental methods will ultimately benefit patients receiving dental implants through improved prevention and treatment of complications. Subsequent research could investigate occlusal effects or whether healing time affects prognosis after induction of peri-implantitis.

Dental implants have a high success and survival rate. However, complications such as peri-implantitis (PI) are highly challenging to treat. PI is characterized by inflammation in the tissues around dental implants with progressive loss of supporting bone. To optimize dental implants' longevity in terms of health and functionality, it is crucial to understand the peri-implantitis pathophysiology. In this regard, using mouse models in research has proven clear benefits in recreating clinical circumstances. This study aimed to describe an experimental model of ligature-induced peri-implantitis in mice and determine whether there is effectiveness in inducing this disease, given the observed bone and tissue changes. The experimental peri-implantitis induction comprehends the following steps: teeth extraction, implant placement, and ligature-inducted PI. A sample of eighteen 3-week-old C57BL/6J male mice was divided into two groups, ligature (N=9) and control non-ligature (N=9). The evaluation of clinical, radiographical, and histological factors was performed. The ligature group showed significantly higher bone loss, increased soft tissue edema, and apical epithelial migration than the non-ligature group. It was concluded that this pre-clinical model can successfully induce peri-implantitis in mice.

Introduction: Periodontitis is a highly prevalent disorder that is increasingly recognized as a risk factor for cerebrovascular disease. In this study we examined the role of periodontitis in the development of cerebral microvascular disease. Methods: Hypertension was induced in aged (17 months old) male C57BL/6J mice via infusion of angiotensin II (ATII) at 1000 ng/kg/min via Alzet pump over 4 weeks. Periodontitis was induced by giving P. gingivalis -LPS (20 μg in 2 μL) injections between the first and second maxillary molars on both the right and left sides twice a week for six weeks. At end of six weeks, we collected mouse brains (N=5 each for Hypertension, Periodontitis, Hypertension + Periodontitis, and Control) and performed standard histology using Prussian blue staining to detect cerebral microhemorrhages (CMH) formation at 20x magnification. The average number, total area, and size of Prussian blue-positive deposits were quantified. Results: ATII-induced hypertension in animals (Systolic blood pressure: 113±2 mmHg to 156±3 mmHg, mean+SE, p<0.0001; Diastolic blood pressure: 82±2 mmHg to 119±3 mmHg, p<0.0001). Presence of hypertension produced significant increase in number of CMH compared to controls (1.97±0.29 per cm 2 vs. 1.24±0.20 per cm 2 , p<0.05). Presence of periodontitis did not alter the number of microhemorrhages (1.68±0.13 per cm 2 vs.1.97±0.29 per cm 2 ). However, size of microhemorrhages doubled in the presence of periodontitis with hypertension (10.58±2.55 μm 2 per cm 2 vs. 5.05±1.15 μm 2 per cm 2 , p<0.05). Conclusions: In this mouse model of ATII-induced hypertension, periodontitis appears to increase size of CMH rather than induce development of new lesions. These findings suggest a role for periodontitis in cerebrovascular disease by modifying and exacerbating pre-existing stroke risk factors rather than acting as an independent risk factor.

Periodontal diseases is a highly prevalent chronic condition regulated by the host immune response to pathogenic bacterial colonization on the teeth surfaces. Nutrition is a critical component in the modulation of the immune system, hence the importance of a balanced diet. With the understanding of how dietary intake composition affects various health outcomes, nutrient diversity has been reported as a modifiable risk factor for periodontal disease. Eating disorders and different dietary patterns can be associated with periodontal diseases. In this sense, balanced and healthy nutrition plays a major role in maintaining the symbiosis between oral microbiota and periodontal health. Therefore, this review seeks to report the associations found in the literature between high- or low-fat/sodium/sugar, eating disorders and periodontal diseases. It was found that some dietary patterns such as high carbohydrate/sugar, high fat, and low fiber intake may be associated with periodontal disease. In addition, the presence of eating disorders can negatively impact patients’ oral health and it is related to the development of several complications, including periodontal diseases. In both situations, nutritional and vitamin deficiencies can aggravate the periodontal condition. However, the relationship between periodontal disease, dietary patterns, and eating disorders still needs more scientific support to be well established, mainly in the sense of pointing out a protective relationship between both.

BackgroundThis study evaluated the antihyperglycemic, anti-bone-resorptive, and anti-inflammatory efficacy of the probiotic Lactobacillus rhamnosus EM1107 in an experimental model of ligature-induced periodontitis in diabetic rats treated with metformin (Met). MethodsA total of 114 male Wistar rats was randomly divided into six groups: (1) control, (2) experimental periodontitis (EP), (3) EP + diabetes mellitus (DM), (4) EP + probiotic (Prob), (5) EP + DM + Prob, and (6) EP + DM + Prob + Met. The animals received probiotic gavage during the 30 days of the experiment. DM was induced on the 14th day of the experiment with a single injection of streptozotocin into the penile vein, followed by ligature for EP induction and Met gavage on the 19th day and euthanasia on the 30th day. Heart blood, gingival and periodontal tissue, and hemimaxillae were collected. Biomolecular analysis, immunoenzymatic assays, histomorphology, and microtomographic analysis were performed. Data were statistically analyzed (p < 0.05). ResultsThere was a significant reduction in interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) in the Prob groups (p < 0.05) as well as in blood glucose levels in the Prob and Met groups (p < 0.001). In addition, histomorphological analysis revealed that the Prob groups had a reduction in inflammatory infiltrate. Tartrate-resistant acid phosphatase (TRAP) and microtomographic analyses showed that the EP/DM/Prob/Met group had significantly lower linear and volumetric bone loss than those who had no treatment (p < 0.01). SOD and GPx immunostaining decreased in all groups receiving probiotics. ConclusionThe findings suggest the immunoinflammatory efficacy of the probiotic L. rhamnosus EM1107 administered either alone or in association with Met in type 1 DM associated with periodontitis.

BACKGROUND To assess the sequelae of coronavirus disease 2019 (COVID-19) and associated factors, such as obesity and periodontitis in adults. METHODS The study included 128 individuals aged ≥35 years with a history of a diagnosis of COVID-19 through real-time polymerase chain reaction (RT-PCR), from Pelotas, Brazil. Self-report sequelae from COVID-19 were defined as the primary outcome. A questionnaire containing sociodemographic, medical, behavioral and self-report of sequelae of COVID-19 was applied. A complete periodontal clinical examination was performed. Weight and height were assessed. Uni-, bi- and multivariate analyses were performed using Poisson regression with robust variance. Additional analyses were performed considering obesity as a subgroup. RESULTS When considering the whole sample, no statistically significant associations between sequelae of COVID-19 with periodontitis (prevalence ratio [PR]:1.14;95% confidence interval [95%CI]: 0.80-1.61) and obesity (0.93 [0.68-1.26]) were identified. In the subgroup analysis, considering only individuals with obesity, those diagnosed with generalized periodontitis had 86% higher probability to have sequelae of COVID-19 when compared to individuals with periodontal health or localized periodontitis. However, when only those without obesity were considered, no significant association with periodontal status was detected (0.82 [0.55-1.23). No significant association with periodontal status were observed when the severity of sequelae (no sequelae, 1 sequela, and >1 sequela) were considered (p > 0.05). CONCLUSIONS Individuals diagnosed with obesity and periodontitis have a higher PR of reporting sequelae from COVID-19 compared to individuals with only obesity.

Cerebral small vessel disease (CSVD) is a term used to describe abnormalities in the intracranial microvasculature affecting small arteries, arterioles, capillaries, and venules. The etiology of these conditions is not fully understood but inflammation appears to play a significant role. Periodontal diseases have been associated with conditions such as stroke and dementia, which are clinical consequences of CSVD. Periodontitis is a highly prevalent chronic multifactorial inflammatory disease regulated by the host immune response against pathogenic bacterial colonization around the teeth. The inflammatory response and the microbial dysbiosis produce pro-inflammatory cytokines that can reach the brain and promote local changes. This review will explore the potential association between periodontitis and CSVD by assessing the impact of periodontitis-induced inflammation and periodontopathogenic bacteria on the underlying mechanisms leading to CSVD. Given the association of periodontitis with stroke and dementia, which are clinical features of CSVD, it may be possible to suggest a link with CSVD. Current evidence linking periodontitis with neuroimaging findings of CSVD enforces the possible link between these conditions.

The aim of the present study was to perform a systematic review of the literature regarding the effect of different mouthwashes on gingival healing after oral surgery in adults. Searches were conducted in seven databases (PubMed/MEDLINE, Cochrane Library, Clinical Trials Registry, Embase, LILACS, Web of Science, and Google Scholar) for relevant randomized controlled trials (RCTs) published up to April 2022. The selection of studies, data extraction, and risk of bias appraisal were performed independently by two reviewers, and a third researcher was consulted to resolve disagreements. Data syntheses were presented narratively for the different criteria of gingival wound healing. Among 4502 articles retrieved from the databases, 13 studies met the eligibility criteria and were included in the present review. Chlorhexidine was the most frequent mouthwash studied (eight studies) and was used in different concentrations and combinations. Cetylpyridinium chloride, H2 Ocean Sea Salt, Commiphora molmol 0.5%, chlorhexidine 0.12%, and essential oils reported better healing than a negative control. However, the uncertain risk of bias in most RCTs included in this review precludes definitive conclusions. Well-designed RCTs are therefore still needed in this area.

FBXO11 is the substrate-recognition component of a ubiquitin ligase complex called SKP1-cullin-F-boxes. The role of FBXO11 in bone development is unexplored. In this study, we reported a novel mechanism of how bone development is regulated by FBXO11. FBXO11 gene knockdown by lentiviral transduction in mouse pre-osteoblast MC3T3-E1 cells leads to reduced osteogenic differentiation, while overexpressing FBXO11 acceler-ates their osteogenic differentiation in vitro. Furthermore, we generated two osteoblastic-specific FBXO11 conditional knockout mouse models, Col1a1-ERT2-FBXO11KO and Bglap2-FBXO11KO mice. In both conditional FBXO11KO mouse models, we found FBXO11 deficiency inhibits normal bone growth, in which the osteogenic activity in FBXO11cKO mice is reduced, while osteoclastic activity is not significantly changed. Mechanistically, we found FBXO11 deficiency leads to Snail1 protein accumulation in osteoblasts, leading to suppression of osteogenic activity and inhibition of bone matrix mineralization. FBXO11 knockdown in MC3T3-E1 cells reduced Snail1 protein ubiquitination and increased Snail1 protein accumulation in the cells, which eventually inhibited osteogenic differentiation. In conclusion, FBXO11 deficiency in osteoblasts inhibits bone formation through Snail1 accumulation, inhibiting osteogenic activity and bone mineralization.