Alveolar Destruction Research Articles

Mechanism Underlying the Alveolar Bone Destruction by Prevotella intermedia: Systematic Review

Introduction: Periodontitis is an inflammatory disorder caused by oral microorganisms, including Prevotella intermedia, that destroy the periodontal ligament and alveolar bone. The detailed mechanism of P. intermedia-inducing bone damage is essential to establish a novel approach to controlling P. intermedia that prevents alveolar bone loss. Purpose: To elucidate the mechanism of P. intermedia's role in alveolar bone destruction by systematically reviewing various related publications. Methods: From September 2020 through February 2021, this systematic review was performed by selecting publications for relevant material from two electronic databases, PubMed and Scopus. The literature must be in English, published within the last ten years, be available in full-text form, and be a research article to meet the criteria for inclusion. Results: Three final articles passed the eligibility evaluation stage and met the inclusion requirements. They all discussed how P. intermedia lipopolysaccharide (LPS) affects target cells to destroy bone, including human dental follicle stem cells (hDFSCs), human periodontal ligament fibroblasts (hPDLs), and macrophages. Tumor necrosis factor (TNF), interleukin-6 (IL-6), IL-8, and prostaglandin E2 (PGE2) are a few of the inflammatory mediators that LPS P. intermedia cause a rise in target cells, leading to bone damage. These inflammatory mediators stimulate nuclear factor-kappa ligand receptor (RANKL) expression, resulting in osteoclast activation and differentiation, leading to bone loss. Conclusion: P. intermedia significantly contributes to alveolar bone degradation by enhancing inflammatory mediators. As observed in periodontitis, these mediators stimulate RANKL expression and osteoclast activation, resulting in alveolar bone damage.

Gut microbiota composition and metabolite profiling in smokers: a comparative study between emphysema and asymptomatic individuals with therapeutic implications

BackgroundDiet has a crucial role in the gut microbiota, and dysbiosis in the gut and lungs has been suggested to be associated with chronic obstructive pulmonary disease. We compared the...

Interactions of Fibroblast Subtypes Influence Osteoclastogenesis and Alveolar Bone Destruction in Periodontitis.

To analyze the fibroblasts subtypes in the gingival tissues of healthy controls, gingivitis and periodontitis patients, as well as the effects of interaction between subtypes on alveolar bone destruction. Gingival tissues were divided into three groups according to clinical and radiographic examination, and the immunostaining of EDA+FN was assessed. Fibroblasts from gingiva developed colony formation units (CFUs) and induced Trap+MNCs. The expression of osteoclastogenesis-related genes was assessed by real-time PCR. Variances in the gene profiles of CFUs were identified by principal component analysis, and cluster analysis divided CFUs into subtypes. The induction of Trap+MNCs and gene expression were compared among individual or cocultured subtypes. The fibroblast subtypes exerted critical effect on Trap+MNCs formation were selected and edited by CRISPR/Cas to investigate the influence on osteoclastogenesis in the periodontitis in mice. Most periodontitis samples exhibited intensive EDA+FN staining (P < 0.05), and these fibroblasts also induced most Trap+MNCs among three groups; consistently, fibroblasts from periodontitis highly expressed genes facilitating osteoclastogenesis. According to gene profiles and osteoclastogenic induction, four clusters of CFUs were identified. The proportion of clusters was significantly different (P < 0.05) among three groups, and their interaction influenced osteoclastogenic induction. Although Cluster 4 induced less osteoclasts, it enhanced the effects of Clusters 1 and 3 on Trap+MNCs formation (P < 0.05). EDA knockout in Cluster 4 abrogated this promotion (P < 0.05), and decreased osteoclasts and alveolar bone destruction in experimental periodontitis (P < 0.05). Heterogeneous fibroblast subtypes affect the switch or development of periodontitis. A subtype (Cluster 4) played important role during alveolar bone destruction, by regulating other subtypes via EDA+FN paracrine.

Critical roles of PU.1/cathepsin S activation in regulating inflammatory responses of macrophages in periodontitis.

To determine the critical roles of PU.1/cathepsin S activation in regulating inflammatory responses of macrophages during periodontitis. Cathepsin S (CatS) is a cysteine protease and exerts important roles in the immune response. Elevated CatS has been found in the gingival tissues of periodontitis patients and is involved in alveolar bone destruction. However, the underlying mechanism of CatS-driven IL-6 production in periodontitis remains unclear. Western blot was applied to measure mature cathepsin S(mCatS) and IL-6 expression in gingival tissues from periodontitis patients and RAW264.7 cells exposed to lipopolysaccharide from Porphyromonas gingivalis (P.g. LPS). Immunofluorescence was applied to confirm the localization of PU.1, and CatS in the gingival tissues of periodontitis patients. ELISA was performed to determine IL-6 production by the P.g. LPS-exposed RAW264.7 cells. Knockdown by shRNA was used to determine the effects of PU.1 on p38/ nuclear factor (NF)-κB activation, mCatS expression and IL-6 production in RAW264.7 cells. The expressions mCatS and IL-6 were significantly upregulated in gingival macrophages. In cultured RAW264.7 cells, increased mCatS and IL-6 protein paralleled the activation of p38 and NF-κB after exposure to P.g. LPS. CatS knockdown by shRNA significantly decreased P.g. LPS-induced IL-6 expression and p38/NF-κB activation. PU.1 was significantly increased in P.g. LPS-exposed RAW264.7 cells, and PU.1 knockdown dramatically abolished the P.g. LPS-induced upregulation of mCatS and IL-6 and the activation of p38 and NF-κB. Furthermore, PU.1 and CatS colocalized in macrophages within the gingival tissues of periodontitis patients. PU.1-dependent CatS drives IL-6 production in macrophages by activating p38 and NF-κB in periodontitis.

Nifedipine attenuates alveolar bone destruction and improves trabecular microarchitectures in mice with experimental periodontitis.

Studies have shown that nifedipine exerts anti-inflammatory and immunosuppressive actions in addition to being a calcium channel blocker. The present study was performed to explore the influence of nifedipine on alveolar bone destruction in mice with experimental periodontitis by evaluating morphological information acquired from micro-computed tomography analysis. BALB/c mice were randomly assigned into four groups: control (C) group; experimental periodontitis (E) group; experimental periodontitis + 10mg/kg dose of nifedipine (EN10) group; and experimental periodontitis + 50mg/kg dose of nifedipine (EN50) group. Periodontitis was induced by oral inoculation with Porphyromonas gingivalis over a 3-week time period. Nifedipine significantly mitigated the loss of alveolar bone height as well as increase of root surface exposure induced by experimental periodontitis. Additionally, the reduction in the bone volume fraction associated with P. gingivalis infection was significantly recovered upon nifedipine treatment. Further, nifedipine attenuated P. gingivalis-induced deteriorations in the trabeculae-associated parameters. Significant difference was evident between Groups EN10 and EN50 in both the extent of alveolar bone loss and microstructural parameters assessed, except trabecular separation and trabecular number. Nifedipine appeared to have good performance in ameliorating bone loss in mice with induced periodontitis. Nifedipine may be utilized in the clinical management of periodontitis, though further research is indicated to verify the therapeutic effect.

Intracellular Drug Delivery Process of Am80-Encapsulated Lipid Nanoparticles Aiming for Alveolar Regeneration.

Chronic obstructive pulmonary disease (COPD) results in obstructive ventilatory impairment caused by emphysema, and current treatment is limited to symptomatic therapy or lung transplantation. Therefore, the development of new treatments to repair alveolar destruction is especially urgent. Our previous study revealed that 1.0 mg/kg of synthetic retinoid Am80 had a repair effect on collapsed alveoli in a mouse model of elastase-induced emphysema. From these results, however, the clinical dose calculated in accordance with FDA guidance is estimated to be 5.0 mg/60 kg, and it is desirable to further reduce the dose to allow the formulation of a powder inhaler for clinical application. To efficiently deliver Am80 to the retinoic acid receptor in the cell nucleus, which is the site of action, we focused on SS-cleavable proton-activated lipid-like material O-Phentyl-P4C2COATSOME®SS-OP, hereinafter referred to as "SS-OP"). In this study, we investigated the cellular uptake and intracellular drug delivery process of Am80-encapsulated SS-OP nanoparticles to elucidate the mechanism of Am80 by nanoparticulation. Am80-encapsulated SS-OP nanoparticles were taken up into the cells via ApoE, and then Am80 was efficiently delivered into the nucleus via RARα. These results indicated the usefulness of SS-OP nanoparticles as drug delivery system carriers of Am80 for COPD treatment.

Magnolia kobus Extract Suppresses Porphyromonas gingivalis LPS-Induced Proinflammatory Cytokine and MMP Expression in HGF-1 Cells and Regulates Osteoclastogenesis in RANKL-Stimulated RAW264.7 Cells.

Clinical prevention is of utmost importance for the management of periodontal diseases. Periodontal disease starts with an inflammatory response in the gingival tissue, and results in alveolar bone destruction and subsequent tooth loss. This study aimed to confirm the anti-periodontitis effects of MKE. To confirm this, we studied its mechanism of action using qPCR and WB in LPS-treated HGF-1 cells and RANKL-induced osteoclasts. We found that MKE suppressed proinflammatory cytokine protein expression by inhibiting the TLR4/NF-κB pathway in LPS-PG-induced HGF-1 cells and blocking ECM degradation by regulating the expression of TIMPs and MMPs. We also confirmed that TRAP activity and multinucleated cell formation were reduced in RANKL-stimulated osteoclasts after exposure to MKE. These results were confirmed by inhibiting TRAF6/MAPK expression, which led to the suppression of NFATc1, CTSK, TRAP, and MMP expression at the gene and protein levels. Our results confirmed that MKE is a promising candidate for the management of periodontal disease based on its anti-inflammatory effects and inhibition of ECM degradation and osteoclastogenesis.

RGS10 Negatively Regulates Apical Periodontitis via TFEB-mediated Autophagy in BABL/c Mice Model and in vitro.

Apical periodontitis is a prevalent oral inflammatory disease that has recently been linked to transcription factor EB (TFEB)-mediated autophagy. Regulator of G-protein signaling 10 (RGS10) is reported to be an effective regulator of the immune system and inflammation. This study aimed to investigate the involvement of RGS10 during the development of apical periodontitis through the TFEB-mediated autophagy signaling pathway. Sixty BALB/c mice were randomly divided into four groups of fifteen mice for the in vivo experiment. Rgs10 was locally overexpressed through eight injections of an adeno-associated virus vector. The model of apical periodontitis was established 21 days following pulp exposure, and the mice were euthanized to obtain mandibles for analysis. Micro-computed tomography was employed to assess alveolar bone destruction, and the levels of Rgs10, TFEB-mediated autophagy signaling factors, and inflammatory factors were measured using quantitative reverse transcription polymerase chain reactions, western blotting, enzyme-linked immunosorbent assays, immunofluorescence, and immunohistochemistry. All experimental results were displayed as images or graphs. For the in vitro experiments, we employed small interfering RNA (siRNA) to silence Rgs10 expression in RAW 264.7 cells. The data were analyzed via one-way ANOVA or Mann-Whitney U test/ Kruskal-Wallis test of variance, where P < 0.05 or U > 1.96 was considered statistically significant. Local overexpression of Rgs10 reduced alveolar bone destruction within the apical periodontitis lesion and significantly decreased macrophage infiltration (P < 0.05). Meanwhile, the expression of TFEB-mediated autophagy signaling factors was upregulated, along with a decrease in inflammatory factor expression (P < 0.05). Lipopolysaccharide-stimulated RAW 264.7 cells exhibited decreased Rgs10 expression and TFEB-mediated autophagy signaling. siRNA-mediated silencing of Rgs10 further suppressed autophagy and concomitantly upregulated inflammatory factors (P < 0.05). Collectively, the findings revealed that RGS10 suppresses the inflammatory response and bone destruction through TFEB-mediated autophagy in apical periodontitis.

Knockdown of SIRT3 perturbs protective effects of irisin against bone loss in diabetes and periodontitis.

A well-recognized risk factor for periodontitis, diabetes mellitus (DM) aggravates periodontal disease with increasing alveolar bone loss. As a novel myokine, irisin is closely linked with bone metabolism. Nonetheless, the effects of irisin on periodontitis under diabetic conditions and the underlying mechanisms remain poorly understood. Here, we showed that local irisin treatment ameliorates alveolar bone loss and oxidative stress, increases SIRT3 expression within periodontal tissues of our experimentally-induced diabetes and periodontitis (DP) rat models. By culturing the periodontal ligament cells (PDLCs) in vitro, we found that irisin could partially rescue inhibited cell viability, mitigate accumulated intracellular oxidative stress, ameliorate mitochondrial dysfunctions, and restore disturbed osteogenic and osteoclastogenic capacities of PDLCs when exposed to high glucose and pro-inflammatory stimulation. Furthermore, lentivirus-mediated SIRT3 knockdown was employed to unravel the underlying mechanism by which SIRT3 mediated irisin's beneficial effects on PDLCs. Meanwhile, in SIRT3-deficient mice, irisin treatment did not protect against alveolar bone destruction and oxidative stress accumulation in DP models, which underlined the crucial role of SIRT3 in mediating the positive effects of irisin on DP. Our findings, for the first time, revealed that irisin attenuates alveolar bone loss and oxidative stress via activation of the SIRT3 signaling cascade, and highlighted its therapeutic potential for the treatment of DP.

Pulmonary Vascular Volume by Quantitative CT in Dyspneic Smokers with Minor Emphysema

Reduced lung diffusing capacity for carbon monoxide (DLCO) at rest and increased ventilation (⩒ E)-carbon dioxide output (⩒CO2) during exercise are frequent findings in dyspneic smokers with largely preserved FEV1. It remains unclear whether low DLCO and high ⩒ E-⩒CO2 are mere reflections of alveolar destruction (i.e. emphysema) or impaired pulmonary perfusion in non-emphysematous tissue contributes to these functional abnormalities. Sixty-four smokers (41 males, FEV1= 84 ± 13%predicted) underwent pulmonary function tests, an incremental exercise test, and quantitative chest computed tomography. Total pulmonary vascular volume (TPVV) was calculated for the entire segmented vascular tree (VIDA Vision™). Using the median % low attenuation area (-950 HU), participants were dichotomized into “Trace” or “Mild” emphysema (E), each group classified into preserved versus reduced DLCO. Within each emphysema subgroup, participants with abnormally low DLCO showed lower TPVV, higher ⩒ E-⩒CO2, and exertional dyspnea than those with preserved DLCO (p < 0.05). TPVV (r = 0.34; p = 0.01), but not emphysema (r = −0.05; p = 0.67), correlated with lower DLCO after adjusting for age and height. Despite lower emphysema burden, Trace-E participants with reduced DLCO had lower TPVV, higher dyspnea, and lower peak work rate than the Mild-E with preserved DLCO (p < 0.05). Interestingly, TPVV (but not emphysema) correlated inversely with both dyspnea-work rate (r = −0.36, p = 0.004) and dyspnea-⩒ E slopes (r = −0.40, p = 0.001). Reduced pulmonary vascular volume adjusted by emphysema extent is associated with low DLCO and heightened exertional ventilation in dyspneic smokers with minor emphysema. Impaired perfusion of non-emphysematous regions of the lungs has greater functional and clinical consequences than hitherto assumed in these subjects.

The role of MIF in periodontitis: A potential pathogenic driver, biomarker, and therapeutic target.

Periodontitis is an inflammatory disease that involves an imbalance in the oral microbiota, activation of inflammatory and immune responses, and alveolar bone destruction. Macrophage migration inhibitory factor (MIF) is a versatile cytokine involved in several pathological reactions, including inflammatory processes and bone destruction, both of which are characteristics of periodontitis. While the roles of MIF in cancer and other immune diseases have been extensively characterized, its role in periodontitis remains inconclusive. In this review, we describe a comprehensive analysis of the potential roles of MIF in periodontitis from the perspective of immune response and bone regulation at the cellular and molecular levels. Moreover, we discuss its potential reliability as a novel diagnostic and therapeutic target for periodontitis. This review can aid dental researchers and clinicians in understanding the current state of MIF-related pathogenesis, diagnosis, and treatment of periodontitis.

Recombinant Irisin Protects Against Alveolar Bone Destruction During Orthodontic Tooth Movement

Patients with periodontitis have higher risk of alveolar bone loss when seek for orthodontic therapy. Inflammation and osteogenesis are key factors in alveolar bone destruction in periodontitis and orthodontic tooth movement (OTM). Here we evaluated the effects of irisin on alveolar bone destruction in rats with periodontitis and OTM. We isolated and cultured human periodontal ligament stem cells (PDLSCs). Irisin was administrated to PDLSCs. Cell proliferations, osteogenic differentiation, expression of RUNX2 and ALP, and the expression of OPG and RANKL were measured. We induced periodontitis and OTM in rats and treated rats with irisin. The alveolar bone loss, inflammatory cytokine levels, and expression of OPG and RANKL in gingival tissues were measured. Irisin promoted the cell proliferation and osteogenic differentiation of PDLSCs. Irisin elevated the expression of RUNX2, ALP, and OPG while decreased the expression of RANKL in PDLSCs. Irisin ameliorated the alveolar bone loss, suppressed cytokine levels, and increased OPG/RANKL expression ratio in rat with periodontitis and orthodontic tooth movement. Irisin prevented alveolar bone destruction during OTM in rats with periodontitis.

Osteogenic mesenchymal stem cells/progenitors in the periodontium.

Periodontitis is the major cause of tooth loss in adults and is mainly characterized by alveolar bone destruction. Elucidating the mesenchymal stem cell (MSC)/progenitor populations of alveolar bone formation will provide valuable insights into regenerative approaches to clinical practice, such as endogenous regeneration and stem-cell-based tissue engineering therapies. Classically, MSCs residing in the bone marrow, periosteum, periodontal ligament (PDL), and even the gingiva are considered to be osteogenic progenitors. Furthermore, the contributions of MSCs expressing specific markers, including Gli1, Axin2, PTHrP, LepR, and α-SMA, to alveolar bone formation have been studied using cell lineage tracing and gene knockout models. In this review, we describe the MSCs/progenitors of alveolar bone and the biological properties of different subpopulations of MSCs involved in alveolar bone development, remodeling, injury repair, and regeneration.

Clindamycin phosphate and bone morphogenetic protein-7 loaded combined nanoparticle-graft and nanoparticle-film formulations for alveolar bone regeneration – An in vitro and in vivo evaluation

Commonly utilized techniques for healing alveolar bone destruction such as the use of growth factors, suffering from short half-life, application difficulties, and the ability to achieve bioactivity only in the presence of high doses of growth factor. The sustained release of growth factors through a scaffold-based delivery system offers a promising and innovative tool in dentistry. Furthermore, it is suggested to guide the host response by using antimicrobials together with growth factors to prevent recovery and achieve ideal regeneration. Herein, the aim was to prepare and an in vitro - in vivo evaluation of bone morphogenetic protein 7 (BMP-7) and clindamycin phosphate (CDP) loaded polymeric nanoparticles, and their loading into the alginate-chitosan polyelectrolyte complex film or alloplastic graft to accelerate hard tissue regeneration. PLGA nanoparticles containing CDP and BMP-7, separately or together, were prepared using the double emulsion solvent evaporation technique. Through in vitro assays, it was revealed that spherical particles were homogeneously distributed in the combination formulations, and sustained release could be achieved for >12 weeks with all formulations. Also, results from the micro-CT and histopathological analyses indicated that CDP and BMP-7 loaded nanoparticle-film formulations were more effective in treatment than the nanoparticle loaded grafts.

Silibinin alleviates inflammation-induced bone loss by modulating biological interaction between human gingival fibroblasts and monocytes.

Silibinin has shown various pharmacological effects that could be attributed to its antioxidant, anti-inflammatory, and immunoregulatory properties. However, the therapeutic potential of silibinin for periodontitis has not been investigated. The therapeutic effects of silibinin in ligation-induced experimental periodontitis were investigated using biochemical, histological, and immunohistochemical methods. The effects of silibinin on the osteoclastogenesis of RAW264.7 cells were investigated using TRAP staining, quantitative polymerase chain reaction (qPCR), pit formation, and immunoblotting. Moreover, its effects on inflammatory cytokine production, RANKL expression, and oxidative stress in lipopolysaccharide (LPS)-stimulated human gingival fibroblasts (HGFs) were evaluated using qPCR and flow cytometry. A coculture system was established to elucidate the effects of silibinin on the crosstalk between LPS-stimulated HGFs and undifferentiated monocytes. Silibinin significantly reduced the alveolar bone loss, decreased the gingival inflammation and RANKL expression, and decreased the RANKL/osteoprotegerin ratio in gingival tissues in experimental periodontitis. The in vitro results showed that silibinin inhibited RANKL-induced osteoclast differentiation and function of RAW264.7 cells and suppressed RANKL-induced nuclear factor of activated T cells 1 (NFATc1) induction and translocation through the nuclear factor-κB and mitogen-activated protein kinase signaling pathways. Silibinin decreased the inflammatory cytokine level and oxidative stress production in LPS-stimulated HGFs; significantly suppressed membrane-bound RANKL expression on LPS-stimulated HGFs; and significantly disrupted TRAP+ cell differentiation in the coculture system. Silibinin effectively inhibits inflammation-induced bone loss in experimental periodontitis based on the regulation of stimulated HGFs by inhibiting the expression of inflammatory and osteoclastogenic mediators. Collectively, targeting the inflamed HGF resolution that mediates osteogenesis may use silibinin as a potential drug-repurposing candidate for modulating alveolar bone destruction in periodontitis. Silibinin effectively inhibits inflammation-induced bone loss in experimental periodontitis based on the regulation of stimulated HGFs by inhibiting the expression of inflammatory and osteoclastogenic mediators.

Comparing gingival inflammation and salivary acidity to hormonal variation during menstruation

IntroductionHormonal changes are associated with healthy female in different stages of her life, such as menarche, pregnancy, and menopause. The main female hormones (i.e., Estrogen and progesterone) act as modulators and effectors during different phases of menstrual cycle. Additionally, these hormones were shown to affect the body inflammatory status. Few studies addressed gingivitis and female hormones. Although gingivitis main cause is dental biofilm, female hormones might modulate this inflammation. If no treatment provided, gingivitis might proceed to periodontitis and alveolar bone destruction may appear. The study aimwas to assess the changes in gingival inflammation, and salivary pH in relation to changes in hormonal levels during different menstrual phases in young females. Method25 healthy young females with regular menstrual cycles were included. The volunteers were invited to visit the clinic during their 2nd day of menstrual cycle (menses phase (MP)). During the visit, plaque index (PLI) and gingival index (GI) were scored. Additionally, salivary pH was calculated. Follow-up readings were taken on the 20th day of menstruation (pre-menstrual phase (PMP)). The difference in PLI, GI and salivary pH was analysed using t-test and chi-square test. ResultsThe study showed that PLI and GI increased statistically significantly with increasing levels of female hormones during PMP and decreased during MP (P-value = 0.012 for PLI and 0.0003 for GI). Salivary pH decreases slightly during PMP and saliva becomes more alkaline during MP (P-value = 0.015). ConclusionThe study showed increased gingival inflammation and plaque accumulation during the premenstrual period. It is recommended to raise awareness of gingival inflammation among adult females to prevent progressive changes of periodontitis. However, due to the limited sample size of this study, a comprehensive population-based study is needed to support the findings.

Chlorhexidine gel topical application ameliorates inflammatory bone loss in experimental periodontitis

This study aimed to evaluate the impact of chlorhexidine (CHX) gel on inflammation-induced periodontal tissue destruction, osteoclastogenesis, subgingival microbiota, and on the modulation of the RANKL/OPG as well as inflammatory mediators during bone remodeling invivo. Ligation- and LPS injection-induced experimental periodontitis were created to investigate the effect of topical application of CHX gel invivo. Alveolar bone loss, osteoclast number and gingival inflammation was evaluated by micro-CT, histological, immunohistochemistry and biochemical analysis. The composition of the subgingival microbiota was characterized by 16S rRNA gene sequencing. Data shows significant decreases in the alveolar bone destruction in rats from ligation-plus-CHX gel group compared to ligation group. In addition, significant decreases in the number of osteoclasts on bone surface and the protein level of receptor activator of nuclear factor κB ligand (RANKL) in gingival tissue were observed in rats from ligation-plus-CHX gel group. Moreover, data shows significantly decreased inflammatory cell infiltration and decreased expression of cyclooxygenase (COX-2) and inducible NO synthase (iNOS) in gingival tissue from ligation-plus-CHX gel group versus ligation group. Assessment of the subgingival microbiota revealed changes in rats with CHX gel application treatment. HX gel presents protective effect on gingival tissue inflammation, osteoclastogenesis, RANKL/OPG expression, inflammatory mediators, and alveolar bone loss invivo, which may have a translational impact on the adjunctive use in the management of inflammation-induced alveolar bone loss.

Aggressive pyogenic granuloma mimicking a malignant lesion: Case report and review.

A pyogenic granuloma is a reactive hyperplastic inflammatory lesion that arises as a result of various stimuli such as low-grade local irritation, trauma, hormones, and certain medications. In the oral cavity, it is a relatively common gingival soft tissue lesion, which originates as an expansile growth of the mucous membrane. It could exhibit aggressive behaviour mimicking that of malignant lesions with different presentations. This article aims to present the case of a patient who attended the dental clinic while complaining about a large and rapidly growing intraoral mass with aggressive behaviour, which had manifested as a fast-growing lesion causing rapid expansion of the buccal and palatal bone, bleeding, and alveolar bone destruction associated with mobile teeth. The article also aims to compare this case with current reported cases of aggressive pyogenic granuloma in the literature.

Role of cathepsin D induced by Porphyromonas gingivalis lipopolysaccharide in periodontitis.

Periodontitis is an inflammatory disease of tooth-supporting tissues caused by oral bacteria. Periodontal ligament loss and alveolar bone destruction occur in progressive periodontitis. Since gingival crevicular fluids (GCF) reflects the inflammatory environment of the periodontal pocket, it is a very important specimen for developing targets for periodontitis diagnosis. An antibody array was performed using GCF collected from healthy participants and patients with periodontitis to identify the proteolytic enzymes involved in periodontitis. Of 21 targets on the antibody array membrane, kallikrein 6 (KLK6), kallikrein 10 (KLK10), cathepsin A (CathA), and cathepsin D (CathD) showed higher levels in periodontitis GCF than in GCF from healthy participants. Lipopolysaccharide stimulation of Porphyromonas gingivalis (PG-LPS) in immortalized gingival fibroblasts only increased CathD protein levels among the four targets. The substrate cleavage activity of CathD was increased in PG-LPS-treated immortalized gingival fibroblast extract. The PG-LPS-induced substrate cleavage effect was abolished by the CathD inhibitor pepstatin A. Osteoclast formation was promoted by treatment with conditioned media from PG-LPS- treated immortalized gingival fibroblasts but inhibited by the CathD inhibitor pepstatin A. These results suggest that PG-LPS affected the osteoclast formation process by increasing CathD expression in cells around the alveolar bone, thereby participating in periodontitis progression.

Naringin protects mice from D-galactose-induced lung aging and mitochondrial dysfunction: Implication of SIRT1 pathways

AimAging is the leading risk factor for diminishing lung function, as well as injury and lung disorder. The target of our research was to examine the potential protective effect of naringin and the possible role of SIRT1 in mice with D-galactose-induced lung aging, by evaluating its effects on antioxidant systems, mitochondrial biogenesis, autophagy, and apoptosis, by referring to the potential involvement of Nrf2/NQO1, LKB1/AMPK/PGC-1α, FOXO1, and P53/caspase-3 signaling. Material and methodsThe mice were randomly sorted into 5 groups (10 each): 1st: normal group received subcutaneous normal saline and intragastric distilled water, 2nd: naringin 300 mg/kg orally, 3rd: D-galactose (200 mg/kg/day) was administered subcutaneously into mice for eight weeks, to accelerate aging, 4th & 5th: oral naringin (150, 300 mg/kg) was given daily concurrently with D-galactose injection for 8 weeks. Key findingIn silico investigation revealed that naringin substantially stimulates the SIRT1 and AMPK molecules. At the molecular level, our findings indicated that treatment with naringin stimulated the mitochondrial biogenesis pathway through regulation of the LKB1/AMPK/PGC-1α signals and upregulated FOXO1-mediated autophagy. Furthermore, naringin exhibited antioxidant properties by activating the Nrf2/NQO1 pathway and inhibiting MDA and AGEs levels. In addition, Naringin ameliorated alveolar spaces destruction and bronchial wall thickening, as well as alleviated P53/caspase-3 apoptosis signaling. SignificanceNaringin exerts protective effects against D-galactose-induced lung aging and enhances longevity by activating SIRT1. SIRT1 regulates various aging-related molecular pathways via restoring pro-oxidant/antioxidant homeostasis, activation of mitochondrial biogenesis, modulating of autophagy and inhibition of apoptosis.