Reactive Oxygen Species-Responsive Pillararene-Embedded Covalent Organic Frameworks with Amplified Antimicrobial Photodynamic Therapy for the Targeted Elimination of Periodontitis Pathogens.

Reactive oxygen species (ROS)-responsive drug delivery systems possess immense potential for targeted delivery and controlled release of therapeutics. However, the rapid responsiveness to ROS and sustained release of antibacterial drugs are often limited by the challenging microenvironment of periodontitis. Integrating ROS-responsive drug delivery systems with photocatalytic technologies presents a strategic approach to overcome these limitations. Herein, a pillararene-embedded covalent organic framework (PCOF) incorporating the antibacterial prodrug thioacetal (TA) has been developed to treat periodontitis. This drug-loaded nanoplatform, namely TA-loaded PCOF, utilizes the self-amplifying ROS property to enhance therapeutic efficacy. PCOFs demonstrate exceptional photosensitivity and ROS generation capabilities when employed as drug carriers. When exposed to ROS, TA within the nanoplatform was activated and cleaved into cinnamaldehyde (CA), a highly potent antibacterial compound. By leveraging visible light to activate the site-specific infection targeting, TA-loaded PCOF effectively alleviated periodontitis, thereby advancing the field of antibacterial drug delivery systems.

Dual-Polymer Functionalized Melanin-AgNPs Nanocomposite with Hydroxyapatite Binding Ability to Penetrate and Retain in Biofilm Sequentially Treating Periodontitis.

Periodontitis is the leading cause of adult tooth missing. Thorny bacterial biofilm and high reactive oxygen species (ROS) levels in tissue are key elements for the periodontitis process. It is meaningful to develop an advanced therapeutic system with sequential antibacterial/ antioxidant ability to meet the overall goals of periodontitis therapy. Herein, a dual-polymer functionalized melanin-AgNPs (P/D-MNP-Ag) with biofilm penetration, hydroxyapatite binding, and sequentially treatment ability are fabricated. Polymer enriched with 2-(Dimethylamino)ethyl methacrylate (D), can be protonated in an acid environment with enhanced positive charge, promoting penetration in biofilm. The other polymer is rich in phosphate group (P) and can chelate Ca2+, promoting the polymer to adhere to the hydroxyapatite surface. Melanin has good ROS scavenging and photothermal abilities, after in situ reduction Ag, melanin-AgNPs composite has sequentially transitioned between antibacterial and antioxidative ability due to heat and acid accelerated Ag+ release. The released Ag+ and heat have synergistic antibacterial effects for bacterial killing. With Ag+ consumption, the antioxidant ability of MNP recovers to scavenge ROS in the inflammatory area. When applied in the periodontitis model, P/D-MNP-Ag has good therapeutical effects to ablate biofilm, relieve inflammation state, and reduce alveolar bone loss. P/D-MNP-Ag with sequential treatment ability provides a reference for developing advanced oral biofilm eradication systems.

C3-targeted therapy in periodontal disease: moving closer to the clinic.

Complement plays a key role in immunosurveillance and homeostasis. When dysregulated or overactivated, complement can become a pathological effector, as seen in several inflammatory disorders, including periodontal disease. Recently, clinical correlative studies and preclinical mechanistic investigations have collectively demonstrated that complement is hyperactivated during periodontitis and that targeting its central component (C3) provides therapeutic benefit in nonhuman primates (NHPs). The preclinical efficacy of a C3-targeted drug candidate combined with excellent safety and pharmacokinetic profiles supported its use in a recent Phase IIa clinical study in which C3 inhibition resolved gingival inflammation in patients with periodontal disease. We posit that C3-targeted intervention might represent a novel and transformative host-modulation therapy meriting further investigation in Phase III clinical trials for the treatment of periodontitis.

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.

The potential use of bacteriophages as antibacterial agents in dental infection.

Dental infections, such as apical Periodontitis, periodontitis, and peri-implantitis (PI), are closely associated with specific bacterial species, including Streptococcus mutans (S. mutans), Porphyromonas gingivalis (P. gingivalis), and Fusobacterium nucleatum (F. nucleatum), among others. Antibiotics are extensively utilized for prophylactic and therapeutic purposes in the treatment of dental infections and other dental-related issues. Unfortunately, the rapid emergence of antimicrobial resistance has accompanied the increased use of antibiotics in recent years. Specific bacterial pathogens have reached a critical stage of antibiotic resistance, characterized by the proliferation of pan-resistant strains and the scarcity of viable therapeutic alternatives. Therapeutic use of particular bacteriophage (phage) particles that target bacterial pathogens is one potential alternative to antibiotics that are now being seriously considered for treating bacterial illnesses. A kind of virus known as a phage is capable of infecting and eliminating bacteria. Because they can't infect cells in plants and animals, phages might be a harmless substitute for antibiotics. To control oral disorders including periodontitis and dental caries, several research have been conducted in this area to study and identify phages from human saliva and dental plaque. The capacity of these agents to disturb biofilms expands their effectiveness against dental plaque biofilms and oral pathogens in cases of periodontitis, PI, and apical periodontitis. This review summarizes the current antibacterial properties of phages used to treat a variety of dental infections, such as periodontitis, peri-implantitis, infected dentin, and apical periodontitis.

Ginsenoside Rb3 alleviates the formation of osteoclasts induced by periodontal ligament fibroblasts in the periodontitis microenvironment through the STAT3 pathway.

This study explores the potential role and mechanism of Ginsenoside Rb3 (Rb3) in modulating osteoclastogenesis induced by human periodontal ligament fibroblasts (hPLFs) within the periodontitis microenvironment. We investigated the anti-inflammatory effects of Rb3 on hPLFs stimulated with Porphyromonas gingivalis lipopolysaccharide (P.g-LPS) utilizing quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay techniques. Moreover, the functional role of Rb3 in hPLFs-induced osteoclast formation was assessed by treating human bone marrow-derived macrophages (hBMMs) with conditioned medium from hPLFs, followed by analyses through qPCR, western blot analysis, and staining for tartrate-resistant acid phosphatase (TRAP) and phalloidin. The impact of Rb3 on the activation of the STAT3 signaling pathway was determined via western blot analysis. Results indicated that Rb3 treatment significantly suppressed the upregulation of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6, MCP-1, and IL-18) at both gene and protein levels in hPLFs induced by P.g-LPS. Furthermore, conditioned medium from Rb3 plus P.g-LPS treated hPLFs notably decreased the number of TRAP-positive cells, actin ring formations, and the expression of osteoclast marker genes (including CTSK, NFATC1, and ACP5). Rb3 also inhibited the P.g-LPS-induced activation of the STAT3 pathway, with the activation of STAT3 partially reversing the effects of Rb3 on inflammation and osteoclast differentiation. Collectively, Rb3 ameliorates inflammation in P.g-LPS-stimulated hPLFs and reduces hPLFs-induced osteoclastogenesis by inhibiting the STAT3 signaling pathway, suggesting its potential as a therapeutic agent for periodontitis.

Streptococcus intermedius causing primary bacterial ventriculitis in a patient with severe periodontitis - a case report.

BACKGROUND: Streptococcus intermedius is a member of the S. anginosus group and is part of the normal oral microbiota. It can cause pyogenic infections in various organs, primarily in the head and neck area, including brain abscesses and meningitis. However, ventriculitis due to periodontitis has not been reported previously. CASE PRESENTATION: A 64-year-old male was admitted to the hospital with a headache, fever and later imbalance, blurred vision, and general slowness. Neurological examination revealed nuchal rigidity and general clumsiness. Meningitis was suspected, and the patient was treated with dexamethasone, ceftriaxone and acyclovir. A brain computer tomography (CT) scan was normal, and cerebrospinal fluid (CSF) Gram staining and bacterial cultures remained negative, so the antibacterial treatment was discontinued. Nine days after admission, the patient's condition deteriorated. The antibacterial treatment was restarted, and a brain magnetic resonance imaging revealed ventriculitis. A subsequent CT scan showed hydrocephalus, so a ventriculostomy was performed. In CSF Gram staining, chains of gram-positive cocci were observed. Bacterial cultures remained negative, but a bacterial PCR detected Streptococcus intermedius. An orthopantomography revealed advanced periodontal destruction in several teeth and periapical abscesses, which were subsequently operated on. The patient was discharged in good condition after one month. CONCLUSIONS: Poor dental health can lead to life-threatening infections in the central nervous system, even in a completely healthy individual. Primary bacterial ventriculitis is a diagnostic challenge, which may result in delayed treatment and increased mortality.

Gallic acid induces osteoblast differentiation and alleviates inflammatory response through GPR35/GSK3ß/ß-catenin signaling pathway in human periodontal ligament cells.

BACKGROUND AND OBJECTIVE: Gallic acid (GA) possesses various beneficial functions including antioxidant, anticancer, anti-inflammatory as well as inhibiting osteoclastogeneis. However, effects on osteogenic differentiation, especially in human ligament periodontal (hPDL) cells, remain unclear. Thus, the aim of this study was to evaluate the function of GA on osteogenesis and anti-inflammation in hPDL cells and to explore the involved underlying mechanism. METHODS: Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) treatment was used as a model for periodontitis. ROS production was determined by H2DCFDA staining. Trans-well and wound healing assays were performed for checking the migration effect of GA. Alizarin red and alkaline phosphatase activity (ALP) assays were performed to evaluate osteogenic differentiation. Osteogenesis and inflammatory-related genes and proteins were measured by real-time PCR and western blot. RESULTS: Our results showed that GA-treated hPDL cells had higher proliferation and migration effect. GA inhibited ROS production-induced by Pg-LPS. Besides, GA abolished Pg-LPS-induced inflammation cytokines (il-6, il-1ß) and inflammasome targets (Caspase-1, NLRP3). In addition, GA promoted ALP activity and mineralization in hPDL cells, lead to enhance osteoblast differentiation process. The effect of GA is related to G-protein-coupled receptor 35 (GPR35)/GSK3ß/ß-catenin signaling pathway. CONCLUSION: GA attenuated Pg-LPS-induced inflammatory responses and periodontitis in hPDL cells. Taken together, GA may be targeted for therapeutic interventions in periodontal diseases.

Interleukin-37 ameliorates periodontitis development by inhibiting NLRP3 inflammasome activation and modulating M1/M2 macrophage polarization.

OBJECTIVE: Our study was designed to explore the role of IL-37 in M1/M2 macrophage polarization imbalance in the pathogenesis of periodontitis. BACKGROUND: Periodontitis is a chronic progressive inflammatory disease featured by gingival inflammation and alveolar bone resorption. Recent research has revealed that regulating macrophage polarization is a viable method to ameliorate periodontal inflammation. IL-37 is an anti-inflammatory cytokine, which has been reported to inhibit innate and adaptive immunity. METHODS: For in vitro experiment, mouse macrophage RAW264.7 cells were pretreated with 0.1 ng/mL recombinant human IL-37. M1 and M2 polarizations of RAW264.7 cells were induced by 100 ng/mL LPS and 20 ng/mL IL-4, respectively. The expression of M1 (iNOS, TNF-α, and IL-6) and M2 (CD206, Arg1, and IL-10) phenotype markers in RAW264.7 cells was detected by RT-qPCR, western blotting, and immunofluorescence staining. For in vivo experiment, experimental periodontitis mouse models were established by sterile silk ligation (5-0) around the bilateral maxillary second molar of mice for 1 week. H&E staining of the maxillary alveolar bone was used to show the resorption of root cementum and dentin. Alveolar bone loss in mouse models was evaluated through micro-CT analysis. The expression of iNOS and CD206 in gingival tissues was assessed by immunohistochemistry staining. NLRP3 inflammasome activation was confirmed by western blotting. RESULTS: IL-37 pretreatment reduced iNOS, TNF-α, and IL-6 expression in LPS-treated RAW264.7 cells but increased CD206, Arg1, and IL-10 in IL-4-treated RAW264.7 cells. LPS-induced upregulation in NLRP3, GSDMD, cleaved-IL-1ß, and cleaved-caspase-1 expression was antagonized by IL-37 treatment. In addition, IL-37 administration ameliorated the resorption of root cementum and dentin in periodontitis mouse models. IL-37 prominently decreased iNOS+ cell population but increased CD206+ cell population in gingival tissues of periodontitis mice. The enhancement in NLRP3, GSDMD, cleaved-IL-1ß, and cleaved-caspase-1 expression in the gingival tissues of periodontitis mice was offset by IL-37 administration. CONCLUSION: IL-37 prevents the progression of periodontitis by suppressing NLRP3 inflammasome activation and mediating M1/M2 macrophage polarization.

Preventive effects of melatonin on periodontal tissue destruction due to psychological stress in rats with experimentally induced periodontitis.

OBJECTIVE AND BACKGROUND: Psychological stress is a potential modifiable environmental risk factor causally related to the exacerbation of periodontitis and other chronic inflammatory diseases. This animal study aimed to investigate comprehensively the preventive efficacy of systemic melatonin administration on the possible effects of restraint stress on the periodontal structures of rats with periodontitis. METHODS: Forty-eight male Sprague Dawley rats were randomly divided into six groups: control, restraint stress (S), S-melatonin (S-Mel), experimental periodontitis (Ep), S-Ep, and S-Ep-Mel. Periodontitis was induced by placing a 3.0 silk suture in a sub-paramarginal position around the cervix of the right and left lower first molars of the rats and keeping the suture in place for 5 weeks. Restraint stress was applied simultaneously by ligation. Melatonin and carriers were administered to the control, S, Ep, and S-Ep groups intraperitoneally (10 mg/body weight/day, 14 days) starting on day 21 following ligation and subjection to restraint stress. An open field test was performed on all groups on day 35 of the study. Periodontal bone loss was measured via histological sections. Histomorphometric and immunohistochemical (RANKL and OPG) evaluations were performed on right mandibular tissue samples and biochemical (TOS (total oxidant status), TAS (total antioxidant status), OSI (oxidative stress index), IL-1ß, IL-10, and IL-1ß/IL-10) evaluations were performed on left mandibular tissue samples. RESULTS: Melatonin significantly limited serum corticosterone elevation related to restraint stress (p < .05). Restraint stress aggravated alveolar bone loss in rats with periodontitis, while systemic melatonin administration significantly reduced stress-related periodontal bone loss. According to the biochemical analyses, melatonin significantly lowered IL-1ß/IL-10, OSI (TOS/TAS), and RANKL/OPG rates, which were significantly elevated in the S-Ep group. CONCLUSION: Melatonin can significantly prevent the limited destructive effects of stress on periodontal tissues by suppressing RANKL-related osteoclastogenesis and oxidative stress.

Effects of amoxicillin and metronidazole as an adjunct to scaling and root planing on glycemic control in patients with periodontitis and type 2 diabetes: A short-term randomized controlled trial.

OBJECTIVE: To assess the effects of amoxicillin and metronidazole with scaling and root planing (SRP) on periodontal parameters and glycemic control in patients with severe periodontitis and diabetes mellitus. BACKGROUND: Adjunctive antibiotics use is advantageous for treating periodontitis in patients with severe periodontitis and diabetes. However, the effects of adjunctive antibiotic use on hemoglobin A1c (HbA1c) levels remain unclear. METHODS: This short-term, randomized controlled trial enrolled patients with severe periodontitis and type 2 diabetes. The patients were randomly allocated to SPR only (i.e., control) or SPR + antibiotics (500 mg of amoxicillin and 200 mg of metronidazole, three times daily for 7 days) groups. Periodontal and hematological parameters were assessed at baseline and 3 months after treatment. Inter- and intra-group analyses were performed using Student's t-tests, Mann-Whitney U tests, and the binary logistic regression models. p-values of <.05 were considered statistically significant. RESULTS: This study enrolled 49 patients, with 23 and 26 patients in the SRP-only and SRP + antibiotics groups, respectively. The periodontal parameters improved significantly and similarly in both groups after treatment (p < .05). The SRP + antibiotics group had more sites of improvement than the SRP-only group when the initial probing depth was >6 mm. (698 [78.96%] vs. 545 [73.35%], p = .008). The HbA1c levels decreased in the SRP-only and SRP + antibiotics groups after treatment (0.39% and 0.53%, respectively). The multivariable binary logistic regression model demonstrated that antibiotics administration and a high baseline HbA1c level were associated with a greater reduction in the HbA1c level (odds ratio = 4.551, 95% confidence interval: 1.012-20.463; odds ratio = 7.162, 95% confidence interval: 1.359-37.753, respectively). CONCLUSIONS: SRP and SRP plus systemic antibiotics were beneficial for glycemic control. Adjunctive antibiotic use slightly improved the outcome for patients with severe periodontitis and poorly controlled diabetes.

Umbelliferone reduces inflammation and ligature-induced osteoclastic alveolar bone resorption in mice.

AIMS: This study aimed to investigate the effects of Umbelliferone (UMB) on the inflammation underlying alveolar bone resorption in mouse periodontitis. METHODS: Male Swiss mice subjected to a ligature of molars were grouped as non-treated (NT), received UMB (15, 45, or 135 mg/kg) or saline daily for 7 days, respectively, and were compared with naïve mice as control. Gingival tissues were evaluated by myeloperoxidase (MPO) activity and interleukin-1ß level by ELISA. The bone resorption was directly assessed on the region between the cement-enamel junction and the alveolar bone crest. Microscopically, histomorphometry of the furcation region, immunofluorescence for nuclear factor-kappa B (NF-ĸB), and immunohistochemistry for tartrate-resistant acid phosphatase (TRAP), and cathepsin K (CTSK) were performed. Systemically, body mass variation and leukogram were analyzed. RESULTS: Periodontitis significantly increased MPO activity, interleukin-1ß level, and NF-ĸB+ immunofluorescence, and induced severe alveolar bone and furcation resorptions, besides increased TRAP+ and CTSK+ cells compared with naïve. UMB significantly prevented the inflammation by reducing MPO activity, interleukin-1ß level, and NF-ĸB+ intensity, besides reduction of resorption of alveolar bone and furcation area, and TRAP+ and CTSK+ cells compared with the NT group. Periodontitis or UMB treatment did not affect the animals systemically. CONCLUSION: UMB improved periodontitis by reducing inflammation and bone markers.

BBR affects macrophage polarization via inhibition of NF-κB pathway to protect against T2DM-associated periodontitis.

BACKGROUND AND OBJECTIVE: Periodontitis is intimately associated with the development of various systemic diseases, among which type 2 diabetes mellitus (T2DM) has a bidirectional relationship with the pathogenesis of periodontitis. The objective of the present work was to investigate the role of berberine (BBR) in periodontitis with T2DM and related mechanisms. METHODS: The mRNA expression of macrophage polarization-related factors in the microenvironment of periodontal inflammation was detected using real-time quantitative PCR (RT-qPCR). The experimental periodontitis model was constructed in wild-type (WT) and T2DM (db/db) mice, which were administered BBR after 7 days of modeling. Alveolar bone loss (ABL) in each group of mice was measured utilizing micro-computed tomography images. RT-qPCR was performed to analyze the levels of macrophage polarization-related factors in mouse gingiva. Lastly, using western blotting and RT-qPCR, the signaling pathway of BBR affecting macrophage polarization in the microenvironment of periodontitis was explored. RESULTS: BBR inhibited M1 polarization and stimulated M2 polarization in the periodontitis microenvironment. BBR decreased ABL in the WT and T2DM periodontitis models. And BBR reduced the production of proinflammatory cytokines and increased anti-inflammatory cytokine expression in the gingiva of WT and T2DM model mice. Ultimately, BBR mediates its anti-inflammatory effects on periodontitis through inhibition of the NF-κB pathway. CONCLUSIONS: BBR had a therapeutic effect on T2DM-associated periodontitis via inhibiting the NF-κB pathway to affect macrophage polarization, which may have implications for the new pharmacological treatment of T2DM-associated periodontitis.

3-methyl-1H-indol-1-yl dimethylcarbamodithioate attenuates periodontitis through targeting MAPK signaling pathway-regulated mitochondrial function.

Periodontitis, the second most common oral disease, is primarily initiated by inflammatory responses and osteoclast differentiation, in which the MAPK signaling pathway and mitochondrial function play important roles. 3-methyl-1H-indol-1-yl dimethylcarbamodithioate (3o), a hybrid of indole and dithiocarbamate, was first synthesized by our group. It has shown anti-inflammatory activity against lipopolysaccharide-induced acute lung injury. However, it is not known if 3o can exert effects in periodontitis. In vitro study: LPS-induced macrophage inflammation initiation and a receptor activator of nuclear factor κB ligand-stimulated osteoclast differentiation model were established. Cell viability, inflammatory cytokines, osteoclast differentiation, the MAPK signaling pathway, and mitochondrial function before and after treatment with 3o were investigated. In vivo study: Alveolar bone resorption, inflammatory cytokine expression, osteoclast differentiation, and the underlying mechanisms were assessed in mice with periodontitis. Inflammatory cytokine expression and osteoclast differentiation appeared downregulated after 3o treatment. 3o inhibited the MAPK signaling pathway and restored mitochondrial function, including mitochondrial reactive oxygen species, mitochondrial membrane potential, and ATP production. Meanwhile, 3o reduced inflammation activation and bone resorption in mice with periodontitis, reflected by the decreased expression of inflammatory cytokines and osteoclasts, implying that 3o inhibited the MAPK signaling pathway and the mitochondrial oxidative DNA damage marker 8-OHdG. These results highlight the protective role of 3o in periodontitis in mice and reveal an important strategy for preventing periodontitis.

Phytocannabinoids and gingival inflammation: Preclinical findings and a placebo-controlled double-blind randomized clinical trial with cannabidiol.

OBJECTIVE: The aim of this study was to: (1) evaluate the anti-inflammatory effects of cannabidiol (CBD) on primary cultures of human gingival fibroblasts (HGFs) and (2) to clinically monitor the effect of CBD in subjects with periodontitis. BACKGROUND: The use of phytocannabinoids is a new approach in the treatment of widely prevalent periodontal disease. MATERIALS AND METHODS: Cannabinoid receptors were analyzed by western blot and interleukin production detected using enzyme immunoassay. Activation of the Nrf2 pathway was studied via monitoring the mRNA level of heme oxygenase-1. Antimicrobial effects were determined by standard microdilution and 16S rRNA screening. In the clinical part, a placebo-control double-blind randomized study was conducted (56 days) in three groups (n = 90) using dental gel without CBD (group A) and with 1% (w/w) CBD (group B) and corresponding toothpaste (group A - no CBD, group B - with CBD) for home use to maintain oral health. Group C used dental gel containing 1% chlorhexidine digluconate (active comparator) and toothpaste without CBD. RESULTS: Human gingival fibroblasts were confirmed to express the cannabinoid receptor CB2. Lipopolysaccharide-induced cells exhibited increased production of pro-inflammatory IL-6 and IL-8, with deceasing levels upon exposure to CBD. CBD also exhibited antimicrobial activities against Porphyromonas gingivalis, with an MIC of 1.5 µg/mL. Activation of the Nrf2 pathway was also demonstrated. In the clinical part, statistically significant improvement was found for the gingival, gingival bleeding, and modified gingival indices between placebo group A and CBD group B after 56 days. CONCLUSIONS: Cannabidiol reduced inflammation and the growth of selected periodontal pathogenic bacteria. The clinical trial demonstrated a statistically significant improvement after CBD application. No adverse effects of CBD were reported by patients or observed upon clinical examination during the study. The results are a promising basis for a more comprehensive investigation of the application of non-psychotropic cannabinoids in dentistry.

Does crocin create new hope for the treatment of oral problems? A focus on periodontitis.

According to the World Health Organization (WHO) reports, oral health has an indispensable role in the maintenance of human public health. However, oral problems, especially periodontitis, are known as bad players in this issue. Periodontitis, as the most prevalent oral disease, is a type of chronic illness mediated by bacterial pathogens and immune system reactions, which is linked with the destruction of tooth-protecting tissues, such as alveolar bone and periodontal ligament. Periodontitis has a high prevalence (over 40% in the United States) and can be associated with other systemic ailments, for instance, arthritis, osteoporosis, metabolic syndrome, cancer, respiratory diseases, chronic kidney disease, and Alzheimer's disease. The common treatments for periodontitis are classified into invasive (surgical) and noninvasive (antibiotic therapy, scaling, and root planning) methods; however, these therapies have not reflected enough effectiveness for related patients. New documents inform the beneficial effects of plant-based compounds in healing various disorders, like periodontitis. In conjunction with this subject, it has been revealed that crocin, as an active component of saffron, regulates the balance between osteoclasts and osteoblasts and has a stroking role in the accumulation of the most common collagen in teeth and bone (type 1 collagen). Besides, this carotenoid compound possesses anti-inflammatory and anti-oxidative effects, which can be associated with the therapeutic processes of crocin in this oral disease. Hence, this narrative review study was performed to reflect the reparative/regenerative aspects of crocin agonist periodontitis.

Expression of TNF-α, omentin-1, and IL-6 before and after adjunctive treatment with a bioactive antimicrobial peptide periodontal gel.

BACKGROUND: The objective of this study was to evaluate and compare the expression levels of TNF-α, omentin-1, and IL-6 in periodontitis patients before and after treatment with biological antimicrobial peptide (AMP) periodontal gel. METHODS: There involved 86 periodontitis patients admitted to our hospital from January 2020 to March 2021. They were equally and randomly distributed into the study group and the control group. The efficacy and adverse reactions were compared between the two groups after treatment, Additionally, the sulcus bleeding index (SBI), plaque index (PLI), gingival index (GI), periodontal probing depth (PD), and levels of TNF-α, omentin-1, and IL-6 were measured before and after treatment. RESULTS: After treatment, the total effective rate of the study group was significantly higher than that of the control group (p < 0.05), while the scores of four indicators (SBI, PLI, GI, and PD) and the levels of TNF-α, omentin-1, and IL-6 in the study group were evidently lower than the control group (p < 0.05). The study group had 1 case of mild irritant reaction, with an adverse reaction rate of 2.33% (1/43). And the control group had 1 case of nausea and 1 case of allergy, with an adverse reaction rate of 4.65% (2/43). The adverse reactions demonstrated no statistical difference between the two groups (χ2 = 0.345, p = 0.557). CONCLUSIONS: The levels of TNF-α and IL-6 were highly expressed before the auxiliary therapy of biological AMP periodontal gel for periodontitis, alongside low expression of omentin-1. Subsequently, the biological antibacterial polypeptide periodontal gel demonstrated efficacy in the treatment of periodontitis.

Synthesis of novel metal silica nanoparticles exhibiting antimicrobial potential and applications to combat periodontitis.

Periodontitis is a severe form of gum disease caused by bacterial plaque that affects millions of people and has substantial worldwide health and economic implications. However, current clinical antiseptic and antimicrobial drug therapies are insufficient because they frequently have numerous side effects and contribute to widespread bacterial resistance. Recently, nanotechnology has shown promise in the synthesis of novel periodontal therapeutic materials. Nanoparticles are quickly replacing antibiotics in the treatment of bacterial infections, and their potential application in dentistry is immense. The alarming increases in antimicrobial resistance further emphasize the importance of exploring and utilizing nanotechnology in the fight against tooth diseases particularly periodontitis. We developed 16 different combinations of mesoporous silica nanomaterials in this study by ageing, drying, and calcining them with 11 different metals including silver, zinc, copper, gold, palladium, ruthenium, platinum, nickel, cerium, aluminium, and zirconium. The antibacterial properties of metal-doped silica were evaluated using four distinct susceptibility tests. The agar well diffusion antibacterial activity test, which measured the susceptibility of the microbes being tested, as well as the antibacterial efficacy of mesoporous silica with different silica/metal ratios, were among these studies. The growth kinetics experiment was used to investigate the efficacy of various metal-doped silica nanoparticles on microbial growth. To detect growth inhibitory effects, the colony-forming unit assay was used. Finally, MIC and MBC tests were performed to observe the inhibition of microbial biofilm formation. Our findings show that silver- and zinc-doped silica nanoparticles synthesized using the sol-gel method can be effective antimicrobial agents against periodontitis-causing microbes. This study represents the pioneering work reporting the antimicrobial properties of metal-loaded TUD-1 mesoporous silica, which could be useful in the fight against other infectious diseases too.

Complement C3 as a potential drug target in periodontitis: Evidence from the cis-Mendelian randomization approach.

AIM: Evidence from a Phase IIa trial showed that a complement C3-targeted drug reduced gingival inflammation in patients with gingivitis. Using drug-target Mendelian randomization (MR), we investigated whether genetically proxied C3 inhibition alters the risk of periodontitis. MATERIALS AND METHODS: We used multiple 'cis' instruments from the vicinity of the encoding loci of C3. Instrument selection was restricted to the drug target encoding loci (chromosome 19; 6,677,715-6,730,573 (GRCh37/hg19)). We selected three uncorrelated single-nucleotide polymorphisms (rs141552034, rs145406915, rs11569479) that were associated with serum C3 levels (p value <1 × 10-4 ) from a genome-wide association study (GWAS) of 5368 European descent individuals. We extracted association statistics from a GWAS of 17,353 clinical periodontitis cases and 28,210 European controls. Wald ratios were combined using inverse-variance weighted meta-analysis to estimate the odds ratio (OR) of the genetically proxied inhibition of C3 in relation to periodontitis. RESULTS: MR analysis revealed that the inhibition of C3 reduces the odds of periodontitis (OR 0.91 per 1 standard deviation reduction in C3; 95% confidence interval 0.87-0.96, p value = .0003). CONCLUSIONS: Findings from our MR analysis suggest a potential protective effect of C3 blockade against periodontitis.

Interleukin-17 alleviates erastin-induced alveolar bone loss by suppressing ferroptosis via interaction between NRF2 and p-STAT3.

AIM: To investigate the relationship between interleukin-17 (IL-17), ferroptosis and osteogenic differentiation. MATERIALS AND METHODS: We first analysed the changes in ferroptosis-related molecules in experimental periodontitis models. The effects of erastin, a small-molecule ferroptosis inducer, and IL-17 on alveolar bone loss and repair in animal models were then investigated. Primary mouse mandibular osteoblasts were exposed to erastin and IL-17 in vitro. Ferroptosis- and osteogenesis-related genes and proteins were detected. Further, siRNA, immunofluorescence co-localization and immunoprecipitation were used to confirm the roles of the nuclear factor erythroid-2-related factor 2 (NRF2) and phosphorylated signal transducer and activator of transcription 3 (p-STAT3), as well as their interaction. RESULTS: The levels of NRF2, glutathione peroxidase 4 and solute carrier family 7 member 11 were lower in the ligated tissues than in normal periodontal tissues. Alveolar bone loss in an in vivo experimental periodontitis model was aggravated by erastin and alleviated by IL-17. In vitro, IL-17 ameliorated erastin-inhibited osteogenic differentiation by reversing ferroptosis. Altered NRF2 expression correlated with changes in ferroptosis-related molecules and osteogenesis. Furthermore, the physical interaction between NRF2 and p-STAT3 was confirmed in the nucleus. In IL-17 + erastin-stimulated osteoblasts, the p-STAT3-NRF2 complex might actively participate in the downstream transcription of ferroptosis- and osteogenesis-related genes. CONCLUSIONS: IL-17 administration conferred resistance to erastin-induced osteoblast ferroptosis and osteogenesis. The possible mechanism may involve p-STAT3 directly interacting with NRF2.