Xenogeneic Collagen Matrix Versus Free Gingival Graft for Augmenting Peri-Implant Keratinized Mucosa Around Dental Implants: A Systematic Review and Meta-Analysis.

OBJECTIVES: There is a growing evidence to suggest augmenting peri-implant keratinized mucosa in the presence of ≤ 2 mm of keratinized mucosa. However, the most appropriate surgical technique and augmentation materials have yet to be defined. The aim of this systematic review and meta-analyses was to evaluate the clinical and patient-reported outcomes of augmenting keratinized mucosa around implants using free gingival graft (FGG) versus xenogeneic collagen matrix (XCM) before commencing prosthetic implant treatment. MATERIAL AND METHODS: Electronic databases were searched to identify observational studies comparing implant sites augmented with FGG to those augmented with XCM. The risk of bias was assessed using the Cochrane Collaboration's Risk of Bias tool. RESULTS: Six studies with 174 participants were included in the present review. Of these, 87 participants had FGG, whereas the remaining participants had XCM. At 6 months, sites augmented with FGG were associated with less changes in the gained width of peri-implant keratinized mucosa compared to those augmented with XCM (mean difference 1.06; 95% confidence interval -0.01 to 2.13; p = 0.05). The difference, however, was marginally significant. The difference between the two groups in changes in thickness of peri-implant keratinized mucosa at 6 months was statistically significantly in favor of FGG. On the other hand, XCM had significantly shorter surgical time, lower postoperative pain score, and higher color match compared to FGG. CONCLUSIONS: Within the limitation of this review, the augmentation of keratinized mucosa using FGG before the placement of the final prosthesis may have short-term positive effects on soft tissue thickness. XCM might be considered in aesthetically demanding implant sites and where patient comfort or shorter surgical time is a priority. The evidence support, however, is of low to moderate certainty; therefore, further studies are needed to support the findings of the present review.

Galectin-3 inhibition alleviated LPS-induced periodontal inflammation in gingival fibroblasts and experimental periodontitis mice.

OBJECTIVES: Clinical studies have confirmed that galectin-3 (Gal-3) levels are significantly elevated in periodontitis patients. The present study aimed to explore the effects of Gal-3 inhibition on periodontal inflammation in vitro and in vivo. METHODS: Human gingival fibroblasts (HGFs) with or without Gal-3 knockdown were stimulated by lipopolysaccharide (LPS), and a ligation-induced mouse periodontitis model treated with a Gal-3 inhibitor was established. Hematoxylin-eosin (H&E) and immunohistochemistry (IHC) staining were used to evaluate Gal-3 levels in gingival tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect Gal-3, interleukin (IL)-6, IL-8, and C-C motif ligand 2 (CCL2) expression. Immunofluorescence and western blotting were used to detect NF-κB and ERK signaling pathway activation. Micro-computed tomography was used to analyse the degree of bone loss. RESULTS: Gal-3 was significantly up-regulated in inflamed gingival tissues and LPS-induced HGFs. Gal-3 knockdown markedly decreased LPS-induced IL-6, IL-8, and CCL2 expression and blocked NF-κB and ERK signaling pathway activation in HGFs. In the mouse periodontitis model, Gal-3 inhibition significantly alleviated IL-1ß and IL-6 infiltration in gingival tissue and mitigated periodontal bone loss. CONCLUSIONS: Gal-3 inhibition notably alleviated periodontal inflammation partly through blocking NF-κB and ERK signaling pathway activation.

Prevalence of Histopathologic Types of Gingival Lesions in the Iranian Population: A 22-Year Retrospective Study.

OBJECTIVES: Gingiva is one of the supporting tissues around the teeth that can be affected by various neoplastic or nonneoplastic lesions. Previous studies have examined several types of gingival lesions, but the lack of a standardized classification system has hindered meaningful comparisons. Additionally, many studies focused primarily on reactive lesions. Our study aims to contribute to the understanding of gingival lesions by investigating their prevalence across age groups, genders, sites, and by their clinical presentation. This research could lead to improved diagnostic accuracy and treatment strategies. MATERIALS AND METHODS: This retrospective study explores the prevalence of gingival lesions based on biopsies during a 22-year span. The patient's demographic details, including age, gender, and lesion's clinical presentation were systematically collected. These lesions were categorized into six groups. Descriptive statistics, χ2 test of independence, and one-way ANOVA were used for data analysis. RESULTS: Among the 7668 biopsied lesions, 684 (8.9%) lesions were located in the gingiva, with a greater occurrence in women (63.5%). Soft tissue tumors represented the most prevalent group in the gingival lesions (72.1%), and peripheral giant cell granuloma (PGCG) was the most frequent lesion (21.2%), followed by, pyogenic granuloma (19.3%), peripheral ossifying fibroma (17.8%) and focal fibrous hyperplasia (7.6%); all of which predominantly affected women, with mean ages falling in the fourth decade of life. Squamous cell carcinoma was recognized as the most common malignancy. CONCLUSION: In this study, PGCG was found to be the most common lesion in the gingiva in Iranian population. Further analysis using a unanimous categorization is required to confirm these results.

Effects of toothpaste containing inactivated Lacticaseibacillus paracasei Probio-01 on plaque-induced gingivitis and dental plaque microbiota.

Plaque-induced gingivitis is an inflammatory response in gingival tissues resulting from bacterial plaque accumulation at the gingival margin. Postbiotics can promote the proliferation of beneficial bacteria and optimise the state of microbiota in the oral cavity. In this study, we investigated the effect of inactivated Lacticaseibacillus paracasei Probio-01 on plaque-induced gingivitis and the dental plaque microbiota. A total of 32 healthy gingival participants (Group N, using blank toothpaste for 3 months) and 60 patients with plaque-induced gingivitis (30 in Group F, using inactivated Probio-01 toothpaste for 3 months, and 30 in Group B, using blank toothpaste for 3 months, respectively) were recruited. Clinical indices, which included bleeding on probing (BOP), gingival index (GI), and plaque index (PI), were used to assess the severity of gingivitis. Furthermore, 16SrDNA amplicon sequencing was used to explore changes in the gingival state and dental plaque microbiota in patients with plaque-induced gingivitis. The results showed that inactivated Probio-01 significantly reduced clinical indices of gingivitis, including BOP, GI, and PI, in participants with plaque-induced gingivitis and effectively relieved gingival inflammation, compared with that observed in the control group (group B). Inactivated Probio-01 did not significantly influence the diversity of dental plaque microbiota, but increased the relative abundance of dental plaque core bacteria, such as Leptotrichia and Fusobacterium (P < 0.05). Strong correlations were observed between the indices and abundance of dental plaque microbiota. Overall, the inactivated Probio-01 significantly reduced the clinical indices of gingivitis and effectively improved gingival inflammation in patients with plaque-induced gingivitis. The activity of inactivated Probio-01 against plaque-induced gingivitis was possibly mediated by its ability to regulate the dental plaque microbiota, as indicated by the close correlation between the plaque microbiota and clinical indices of gingivitis.

Ceramic soft tissue trimming bur gingival depigmentation: clinical performance and patient experience. A split mouth randomized controlled trial.

BACKGROUND: The ceramic soft tissue trimming bur (CeraTip™) was initially introduced for use in gingivoplasty but has recently been used for gingival depigmentation. The aim of this study is to compare the efficacy of depigmentation between the novel CeraTip™ and the gold-standard surgical scalpel technique. METHODS: Eight healthy, nonsmokers with moderate to severe gingival hyperpigmentation in both arches were randomly assigned for CeraTip™ depigmentation in one arch as the test group (TG) and scalpel depigmentation in the opposite arch as the control group (CG). Pigmentation indices were used to assess clinical performance. Treatment time, pain level, and esthetic satisfaction were the parameters of patient experience. The assessments were performed at baseline, one week, one month, and three months. RESULTS: At all assessment visits, pigmentation intensity represented by the Dummet oral pigmentation index (DOPI), and pigmentation distribution represented by the Hedin melanin index (MI), were significantly lower than those at baseline (p < 0.001) in both groups. When comparing the two groups, Scalpel depigmentation had better initial clinical outcomes, while CeraTip™ had less visible repigmentation, pain scores, treatment time, and greater esthetic satisfaction. However, none of the differences were statistically significant. CONCLUSION: Both techniques successfully removed gingival hyperpigmentation with comparable clinical performance. The patients preferred CeraTip™ depigmentation. TRIAL REGISTRATION: The study protocol was registered on 11/09/2023 on the www. CLINICALTRIALS: gov database (NCT06031116) after the approval of the Ethics Committee, Faculty of Dentistry, Ain Shams University (FDASU-Rec012124).

Gingiva squamous-cell carcinoma in a non-smoking patient with occupational exposure to solvent siphoning using mouth: case report and literature review.

Background: While overall head and neck cancer incidence decreases due to reduced tobacco and alcohol consumption, the incidence of HPV negative oral cavity squamous cell carcinoma (SCC) is raising in several industrialized countries, especially in non-smoking and non-drinking patients. Case presentation: We document a case of gingiva SCC in a 56 years old never-smoker patient reporting low alcohol consumption and unusual occupational solvent exposure. The HPV-negative lesion was surgically removed in 2018, and the patient remains in complete remission 4 years after recurrent surgery in 2019. In 2021, the patient was referred to the occupational cancer consultation. The patient worked as screen printer for 18 years. He reported mouth siphoning every 2-3 days to transfer organic solvents (mainly aromatic hydrocarbons and ketones) from containers into smaller recipients, with regular passage of solvents into his mouth. Conclusion: According to the literature, the frequency of solvent siphoning using mouth is likely to be underestimated. While our review did not find studies reporting longterm consequences to the oral cavity of mouth siphoning, current evidence supports a positive association of upper aero digestive tract SCC with occupational exposures to organic solvents and printing processes. In absence of major extraprofessional factors, the HPV-negative gingiva SCC of this patient might be attributable to the regular occupational oral solvent exposure. While the available evidence remains limited to formally establish a causal relationship, clinicians should investigate this hazardous work practice in patients with OSCC and history of solvent exposures.

[Dental gel Cholisal at the stage of conservative treatment of inflammatory periodontal diseases]. / Klinicheskaya effektivnost' konservativnogo lecheniya patsientov s khronicheskim generalizovannym parodontitom s primeneniem gelya Kholisal.

PURPOSE OF THE STUDY: To study the effectiveness of the drug Cholisal as part of the conservative treatment of chronic periodontitis. MATERIAL AND METHODS: We selected 100 patients aged 35 to 65 years of both sexes with a diagnosis of moderate chronic periodontitis in the acute stage with a periodontal pocket depth of 3.5-5 mm. Depending on the tactics of conservative treatment of periodontitis, patients were divided into two groups of 50 people. In the main group, Cholisal dental gel was used as part of complex conservative treatment, and in the control group, Metrogil-denta gel was used. To assess the effectiveness of treatment, a dental examination of patients was carried out with an index assessment of the condition of periodontal tissues and a biochemical analysis of the content of arachidonic acid and prostaglandin E2 in gingival blood, comparing the indicators before treatment and 14 days after the start of treatment. RESULTS: When the drug Cholisal was included in complex treatment, 14 days from the start of treatment, patients experienced a statistically significant decrease in the depth of periodontal pockets from 4.7±0.32 mm to 3.6±0.19, and the Green-Vermillion hygiene index by 60.7%, Silness-Loe plaque index by 73.1%, PMA index by 68.8%, Muhlemann-Cowell bleeding index by 68.0% (p<0.001 compared to baseline). When Metrogil-denta gel was used in complex therapy, the effectiveness of treatment was lower: the depth of periodontal pockets did not change significantly (from 4.5±0.22 mm to 4.2±0.17 mm, p>0.05), reduction in the hygiene index Green-Vermillion was 51.9%, Silness-Loe plaque index - 64.0%, PMA index - 43.7%, Muhlemann-Cowell bleeding index - 45.8% (p<0.001 compared to baseline, p<0.001 compared to the main group). A laboratory study showed that in patients of the main group, after completing a course of conservative treatment, the content of biomarkers of inflammation significantly decreased compared to the initial level (p<0.05), while in patients of the control group the content of arachidonic acid and prostaglandin E2 in the gingival blood during the study period did not change significantly (p>0.05 compared to the initial level). CONCLUSIONS: The use of the drug Cholisal in the conservative treatment of chronic periodontitis has demonstrated more pronounced positive dynamics of clinical and biochemical parameters compared to traditional therapy, which suggests its high effectiveness.

Th17-to-Tfh plasticity during periodontitis limits disease pathology.

Th17 cell plasticity is crucial for development of autoinflammatory disease pathology. Periodontitis is a prevalent inflammatory disease where Th17 cells mediate key pathological roles, yet whether they exhibit any functional plasticity remains unexplored. We found that during periodontitis, gingival IL-17 fate-mapped T cells still predominantly produce IL-17A, with little diversification of cytokine production. However, plasticity of IL-17 fate-mapped cells did occur during periodontitis, but in the gingiva draining lymph node. Here, some Th17 cells acquired features of Tfh cells, a functional plasticity that was dependent on IL-6. Notably, Th17-to-Tfh diversification was important to limit periodontitis pathology. Preventing Th17-to-Tfh plasticity resulted in elevated periodontal bone loss that was not simply due to increased proportions of conventional Th17 cells. Instead, loss of Th17-to-Tfh cells resulted in reduced IgG levels within the oral cavity and a failure to restrict the biomass of the oral commensal community. Thus, our data identify a novel protective function for a subset of otherwise pathogenic Th17 cells during periodontitis.

Idiopathic gingival fibromatosis and primary analysis of dominant bacteria in subgingival biofilm: a case report.

Idiopathic gingival fibromatosis (IGF), a rare fibroproliferative disease of unknown etiology, affects gingival tissue and has substantial adverse effects on patients. Therefore, the pathogenesis of IGF requires more extensive and in-depth research. In this case, a patient with confirmed IGF underwent initial nonsurgical periodontal therapy and gingivectomy, and the prognosis was good. The patient had no loss of periodontal attachment but had a history of swelling and bleeding of the gingiva prior to fibrous enlargement, which prompted further investigation. We explored the patient's subgingival microbiome and found a high abundance of periodontal pathogens. Gingival tissue biopsy revealed abundant fibrous tissue containing multiple inflammatory cell infiltrates. These results suggest that gingival inflammation secondary to periodontal pathogens can contribute to IGF onset.

Analysis of inflammation and bone remodeling of atmospheric plasma therapy in experimental periodontitis.

BACKGROUND AND OBJECTIVE: The biological effects of atmospheric plasma (cold plasma) show its applicability for controlling the etiological factors that involve tissue repair. Thus, the study evaluated the effect of atmospheric plasma therapy in the control of tissue inflammation and bone remodeling in experimental periodontitis. METHODS: Fifty-six rats were subjected to ligation in the cervical region of the first maxillary molars (8 weeks). The animals were divided into two groups (n = 28): periodontitis without treatment group (P group), and periodontitis with atmospheric plasma treatment group (P + AP group). Tissue samples were collected at 2 and 4 weeks after treatment to analyze the inflammation and bone remodeling by biochemical, histomorphometric, and immunohistochemical analyses. RESULTS: Inflammatory infiltration in the gingival and periodontal ligament was lower in the P + AP group than in the P group (p < .05). The MPO and NAG levels were higher in the P + AP group compared to P group (p < .05). At 4 weeks, the TNF-α level was lower and the IL-10 level was higher in the P + AP group compared to P group (p < .05). In the P + AP group, the IL-1ß level increased in the second week and decreased in the fourth week (p < .05), the number of blood vessels was high in the gingival and periodontal ligament in the second and fourth week (p < .05); and the number of fibroblasts in the gingival tissue was low in the fourth week, and higher in the periodontal tissue in both period (p < .05). Regarding bone remodeling, the RANK and RANKL levels decreased in the P + AP group (p < .05). The OPG level did not differ between the P and P + AP groups (p > .05), but decreased from the second to the fourth experimental week in P + AP group (p < .05). CONCLUSIONS: The treatment of experimental periodontitis with atmospheric plasma for 4 weeks modulated the inflammatory response to favor the repair process and decreased the bone resorption biomarkers, indicating a better control of bone remodeling in periodontal disease.

Combined use of hydrogen-rich water and enzyme-digested edible bird's nest improves PMA/LPS-impaired wound healing in human inflammatory gingival tissue equivalents.

Gingival wound healing plays a critical role in maintaining oral health. However, this process can be delayed by oxidative stress and excessive inflammatory responses. In this study, we established a human inflammatory gingival tissue equivalent (iGTE) to investigate the inhibitory effects of hydrogen-rich water (HW), enzyme-digested edible bird's nest (EBND) and sialic acid (SA) on PMA (an inducer of oxidative free radicals)- and LPS (an inflammatory stimulus)-impaired wound healing. The iGTE was constructed by human gingival fibroblasts (hGFs), keratinocytes and macrophages under three-dimensional conditions. Wounds in the iGTE and hGF/keratinocyte monolayers were created by mechanical injury. Tissues and cells were pretreated with HW, EBND, and SA, and then exposed to the inflammatory and oxidative environment induced by PMA (10 ng/mL) and LPS (250 ng/mL). The inflammatory cytokines IL-6 and IL-8 were quantitatively analyzed by ELISA. Histopathological image analysis was performed by HE and immunofluorescence staining. In the iGTE, PMA/LPS significantly reduced the epithelial thickness while causing a decrease in K8/18, E-cadherin, laminin and elastin expression and an increase in COX-2 expression along with ulcer-like lesions. In mechanically scratched hGFs and keratinocyte monolayers, PMA/LPS significantly impaired wound healing, and promoted the secretion of IL-6 and IL-8. Pretreatment of HW, EBND, and SA significantly suppressed PMA/LPS-induced wound healing delay and inflammatory responses in cell monolayers, as well as in the iGTE. Remarkably, the combined use of HW and EBND exhibited particularly robust results. Combined use of HW and EBND may be applied for the prevention and treatment of wound healing delay.

PGRN is involved in macrophage M2 polarization regulation through TNFR2 in periodontitis.

BACKGROUND AND OBJECTIVE: Progranulin (PGRN), a multifunctional growth factor, plays indispensable roles in the regulation of cancer, inflammation, metabolic diseases, and neurodegenerative diseases. Nevertheless, its immune regulatory role in periodontitis is insufficiently understood. This study attempts to explore the regulatory effects of PGRN on macrophage polarization in periodontitis microenvironment. METHODS: Immunohistochemical (IHC) and multiplex immunohistochemical (mIHC) stainings were performed to evaluate the expression of macrophage-related markers and PGRN in gingival samples from periodontally healthy subjects and periodontitis subjects. RAW264.7 cells and bone marrow-derived macrophages (BMDMs) were polarized towards M1 or M2 macrophages by the addition of LPS or IL-4, respectively, and were treated with or without PGRN. Real-time fluorescence quantitative PCR (qRT-PCR), immunofluorescence staining (IF), enzyme-linked immunosorbent assay (ELISA), and flow cytometry were used to determine the expressions of M1 and M2 macrophage-related markers. Co-immunoprecipitation was performed to detect the interaction between PGRN and tumor necrosis factor receptor 2 (TNFR2). Neutralizing antibody was used to block TNFR2 to confirm the role of TNFR2 in PGRN-mediated macrophage polarization. RESULTS: The IHC and mIHC staining of human gingival slices showed a significant accumulation of macrophages in the microenvironment of periodontitis, with increased expressions of both M1 and M2 macrophage markers. Meanwhile, PGRN was widely expressed in the gingival tissue of periodontitis and co-expressed mainly with M2 macrophages. In vitro experiments showed that in RAW264.7 cells and BMDMs, M1 markers (CD86, TNF-α, iNOS, and IL-6) substantially decreased and M2 markers (CD206, IL-10, and Arg-1) significantly increased when PGRN was applied to LPS-stimulated macrophages relatively to LPS stimulation alone. Besides, PGRN synergistically promoted IL-4-induced M2 markers expression, such as CD206, IL-10, and Arg1. In addition, the co-immunoprecipitation result showed the direct interaction of PGRN with TNFR2. mIHC staining further revealed the co-localization of PGRN and TNFR2 on M2 macrophages (CD206+). Blocking TNFR2 inhibited the regulation role of PGRN on macrophage M2 polarization. CONCLUSIONS: In summary, PGRN promotes macrophage M2 polarization through binding to TNFR2 in both pro- and anti-inflammatory periodontal microenvironments.

Gingival proteomics reveals the role of TGF beta and YAP/TAZ signaling in Raine syndrome fibrosis.

Raine syndrome (RNS) is a rare autosomal recessive osteosclerotic dysplasia. RNS is caused by loss-of-function disease-causative variants of the FAM20C gene that encodes a kinase that phosphorylates most of the secreted proteins found in the body fluids and extracellular matrix. The most common RNS clinical features are generalized osteosclerosis, facial dysmorphism, intracerebral calcifications and respiratory defects. In non-lethal RNS forms, oral traits include a well-studied hypoplastic amelogenesis imperfecta (AI) and a much less characterized gingival phenotype. We used immunomorphological, biochemical, and siRNA approaches to analyze gingival tissues and primary cultures of gingival fibroblasts of two unrelated, previously reported RNS patients. We showed that fibrosis, pathological gingival calcifications and increased expression of various profibrotic and pro-osteogenic proteins such as POSTN, SPARC and VIM were common findings. Proteomic analysis of differentially expressed proteins demonstrated that proteins involved in extracellular matrix (ECM) regulation and related to the TGFß/SMAD signaling pathway were increased. Functional analyses confirmed the upregulation of TGFß/SMAD signaling and subsequently uncovered the involvement of two closely related transcription cofactors important in fibrogenesis, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). Knocking down of FAM20C confirmed the TGFß-YAP/TAZ interplay indicating that a profibrotic loop enabled gingival fibrosis in RNS patients. In summary, our in vivo and in vitro data provide a detailed description of the RNS gingival phenotype. They show that gingival fibrosis and calcifications are associated with, and most likely caused by excessed ECM production and disorganization. They furthermore uncover the contribution of increased TGFß-YAP/TAZ signaling in the pathogenesis of the gingival fibrosis.

[A preliminary in vivo and in vitro study of endothelial cell pyroptosis in the periodontal inflammatory environment].

Objective: To observe whether endothelial cells undergo pyroptosis in the inflammatory periodontal environment by using a model in vivo and in vitro, providing an experimental basis for indepth understanding of the underlying pathogenesis of periodontitis. Methods: According to the classification of periodontal diseases of 2018, gingival tissues were collected from periodontally healthy subjects and patients with stage Ⅲ-Ⅳ, grade C periodontitis, who presented Department of Oral and Maxillofacial Surgery and Department of Periodontology, School of Stomatology, The Fourth Military Medical University from April to May 2022. Immunohistochemical staining was performed to detect the expression level and distribution of gasdermin D (GSDMD), a hallmark protein of cell pyroptosis, in gingival tissues. Periodontitis models were established in each group by ligating the maxillary second molar teeth of three mice for 2 weeks (ligation group). The alveolar bone resorption was determined by micro-CT (mice without ligation treatment were used as the control group), and the colocalization of GSDMD and CD31 were quantitatively analyzed by immunofluorescence staining in gingival tissues of healthy and inflammatory mice. Human umbilical vein endothelial cells (HUVECs) were cultured in vitro and treated with lipopolysaccharide (LPS) of Porphyromonas gingivalis (Pg) combined with adenosine triphosphate (ATP) at various concentrations of 0.5, 1.0, 2.5, 5.0, and 10.0 mg/L, respectively, and the 0 mg/L group was set as the control group at the same time. Scanning electron microscopy was used to observe the morphology of HUVECs. Western blotting was used to detect the expression of gasdermin D-N terminal domains (GSDMD-N) protein and immunofluorescence cell staining was used to detect the expression and distribution of GSDMD. Cell counting kit-8 (CCK-8) was used to detect the proliferative ability of HUVECs, and propidium iodide (PI) staining was used to detect the integrity of cell membrane of HUVECs. Results: Immunohistochemistry showed that GSDMD in gingival tissues of periodontitis was mainly distributed around blood vessels and its expression level was higher than that in healthy tissues. Micro-CT showed that alveolar bone resorption around the maxillary second molar significantly increased in ligation group mice compared with control subjects (t=8.88, P<0.001). Immunofluorescence staining showed significant colocalization of GSDMD with CD31 in the gingival vascular endothelial cells in mice of ligation group. The results of scanning electron microscopy showed that there were pores of different sizes, the typical morphology of pyroptosis, on HUVECs cell membranes in the inflammatory environment simulated by ATP combined with different concentrations of LPS, and 2.5 mg/L group showed the most dilated and fused pores on cell membranes, with the cells tended to lyse and die. Western blotting showed that the expression of GSDMD-N, the hallmark protein of cell pyroptosis, was significantly higher in 2.5 and 5.0 mg/L groups than that in the control group (F=3.86, P<0.01). Immunofluorescence cell staining showed that the average fluorescence intensity of GSDMD in 2.5 mg/L group elevated the most significantly in comparison with that in the control group (F=35.25, P<0.001). The CCK-8 proliferation assay showed that compared to the control group (1.00±0.02), 0.5 mg/L (0.52±0.07), 1.0 mg/L (0.57±0.10), 2.5 mg/L (0.58±0.04), 5.0 mg/L (0.55±0.04), 10.0 mg/L (0.61±0.03) groups inhibited cell proliferation (F=39.95, P<0.001). PI staining showed that the proportion of positive stained cells was highest [(56.07±3.22)%] in 2.5 mg/L group (F=88.24, P<0.001). Conclusions: Endothelial cells undergo significant pyroptosis in both in vivo and in vitro periodontal inflammatory environments, suggesting that endothelial cell pyroptosis may be an important pathogenic factor contributing to the pathogenesis of periodontitis.

miRNA-148a-containing GMSC-derived EVs modulate Treg/Th17 balance via IKKB/NF-κB pathway and treat a rheumatoid arthritis model.

Mesenchymal stem cells (MSCs) have demonstrated potent immunomodulatory properties that have shown promise in the treatment of autoimmune diseases, including rheumatoid arthritis (RA). However, the inherent heterogeneity of MSCs triggered conflicting therapeutic outcomes, raising safety concerns and limiting their clinical application. This study aimed to investigate the potential of extracellular vesicles derived from human gingival mesenchymal stem cells (GMSC-EVs) as a therapeutic strategy for RA. Through in vivo experiments using an experimental RA model, our results demonstrate that GMSC-EVs selectively homed to inflamed joints and recovered Treg and Th17 cell balance, resulting in the reduction of arthritis progression. Our investigations also uncovered miR-148a-3p as a critical contributor to the Treg/Th17 balance modulation via IKKB/NF-κB signaling orchestrated by GMSC-EVs, which was subsequently validated in a model of human xenograft versus host disease (xGvHD). Furthermore, we successfully developed a humanized animal model by utilizing synovial fibroblasts obtained from patients with RA (RASFs). We found that GMSC-EVs impeded the invasiveness of RASFs and minimized cartilage destruction, indicating their potential therapeutic efficacy in the context of patients with RA. Overall, the unique characteristics - including reduced immunogenicity, simplified administration, and inherent ability to target inflamed tissues - position GMSC-EVs as a viable alternative for RA and other autoimmune diseases.

Regulatory role of PDK1 via integrated gene analysis of mitochondria-immune response in periodontitis.

AIMS: To investigate the association between mitochondrial events and immune response in periodontitis and related regulatory genes. MAIN METHODS: Gene expression profiles in gingival tissues were retrieved from the Gene Expression Omnibus. Mitochondria-immune response-related differentially expressed genes (MIR-DEGs) between the healthy and periodontitis samples were determined. WGCNA, GO, and KEGG were used to investigate the function and the enriched pathways of MIR-DEGs. The correlation between MIR-DEGs expression and clinical probing pocket depth was analyzed. The MIR-DEGs were further identified and verified in animal samples. A periodontitis model was established in C57BL/6 mice with silk ligation. Micro-computed tomography was used to assess alveolar bone loss. Western blot, quantitative real-time polymerase chain reaction, and immunohistochemical analyses further validated the differential expression of the MIR-DEGs. KEY FINDINGS: A total of ten MIR-DEGs (CYP24A1, PRDX4, GLDC, PDK1, BCL2A1, CBR3, ARMCX3, BNIP3, IFI27, and UNG) were identified, the expression of which could effectively distinguish patients with periodontitis from the healthy controls. Enhanced immune response was detected in the periodontitis group with that in the healthy controls, especially in B cells. PDK1 was a critical MIR-DEG correlated with B cell immune response and clinical periodontal probing pocket depth. Both animal and clinical periodontal samples presented higher gene and protein expression of PDK1 than the control samples. Additionally, PDK1 colocalized with B cells in both animal and clinical periodontal tissues. SIGNIFICANCE: Mitochondria participate in the regulation of the immune response in periodontitis. PDK1 may be the key mitochondria-related gene regulating B-cell immune response in periodontitis.

Multivariate analysis of the effect of keratinized mucosa on peri-implant tissues with platform switching: A retrospective study.

BACKGROUND: In recent years, platform switching implant treatment has been increasing, which is believed to minimize bone loss around the implant after placement. However, there have been no reports on the relationship between keratinized mucosa width (KMW) and bone loss and soft tissue recession in platform switching implants. OBJECTIVE: We evaluated the effect of the KMW on the amount of bone loss and soft tissue recession around a platform switching implant retrospectively using multivariate analysis. MATERIALS AND METHODS: This one-year retrospective study included 91 implants in 48 patients. Age, sex, a history of periodontitis, implant location, oral hygiene status, and the KMW were included as explanatory variables to evaluate bone loss (BL) and buccal gingival height (GH). Generalized estimating equations (GEEs) were used to evaluate the effect of the KMW on platform switching peri-implant tissues. RESULTS: The mean bone loss on the mesial (ΔBLm), distal (ΔBLd), and buccal (ΔBLb) sides of the implant were 0.16 ± 0.27 mm, 0.19 ± 0.34 mm, and 0.24 ± 0.50 mm, respectively, at 1 year after superstructure placement. The mean amount of change of GH (ΔGH) on the buccal side was 0.30 ± 0.47 mm. After correcting for confounders using GEEs, the results suggested that KMW <1.5 mm was a significant factor (P < 0.001) for bone loss over time in ΔBLm, ΔBLd, and ΔBLb. In addition, for soft tissues on the buccal side, KMW <1.5 mm was a significant factor for ΔGH reduction over time (P < 0.001). CONCLUSIONS: Keratinized mucosa width ≥1.5 mm was associated with a higher probability less hard and soft tissue recession around the platform switching implant after 1 year from superstructure placement.

Giant cell angiofibroma of gingiva in tuberous sclerosis complex: a case report and literature review.

BACKGROUND: Tuberous sclerosis complex (TSC) is a rare, complex genetic disorder characterized by hamartomas and neoplastic lesions in various organ systems. With the development of radiology and gene testing, the diagnostic criteria for TSC were updated in 2012 at the International Consensus Conference. Intraoral fibromas have long been associated with TSC. However, the incidence of giant cell angiofibroma (GCA) in TSC patients is extremely rare. Here, we report the first case of GCA in the gingival tissue of a patient with TSC. CASE PRESENTATION: A 41-year-old woman first visited the Department of Oral and Maxillofacial Surgery, Chonnam National University Dental Hospital, complaining of gingival enlargement. Clinical examination revealed several manifestations associated with TSC, including intraoral fibromas, facial angiofibromas, dental enamel pits, ungual fibromas, "confetti" skin lesions, hypomelanotic macules, and a shagreen patch. Intraoral examination revealed a 6.0 × 5.0 cm gingival overgrowth on the left mandible. Surgical excision was performed, and subsequent histopathological examination confirmed the diagnosis of GCA. There was no evidence of recurrence within the 24- months of surgery. CONCLUSIONS: We report the first case of GCA in the gingival tissue of a patient with TSC. This report would contribute to an improved understanding of this rare disease. However, further case reports are necessary to clarify the relationship between GCA and TSC.

Metastatic Maxillary Gingival Angiosarcoma with Aggressive Growth: A Case Report.

Angiosarcoma is a rare malignant tumor of endothelial origin. It is an aggressive neoplasm with early metastasis and poor prognosis and accounts for approximately 2% of all soft tissue sarcomas. Primary tumors arising in the oral cavity account for only 1% of all angiosarcomas. Here, we report a rare case of metastatic angiosarcoma of the gingiva originating from a primary mediastinal lesion. The patient was an 83-year-old man who presented with a maxillary interincisor tumor; it was a painless mass with rounded superficial necrosis measuring 23 mm× 17 mm on the labial side and 20 mm× 17 mm on the palatal side. The histopathological diagnosis was of an epithelioid angiosarcoma. Imaging revealed lesions in the mediastinum, lungs, liver, and skin. The primary lesion was considered a mediastinal lesion. As the tumor had spread throughout the body, palliative therapy was administered. However, the patient's general condition deteriorated rapidly, and he died 3 weeks after the first visit. Identifying oral metastatic malignancies may result in detection of malignant tumors at other sites; thus, oral and maxillofacial surgeons must maintain a heightened awareness of angiosarcoma.