Computational study of Cu2+, Fe2+, Mn2+, Mn3+, Fe3+, CrO42-, Si4+, and Hg+ binding sites identification on cytokines to predict dental metal allergy: An in silico study.

Context: Metal allergy is a general term to describe allergic diseases due to the release of metal ion reactions in the body which are mediated by T cells and involve inflammatory cytokines that can cause morbidity and mortality. Molecular docking is an analysis that can be used to assess the interaction of ligand bonds with target proteins that are used to predict metal allergies caused by metal ions that stimulate cytokines. Aims: To analyze the binding sites of Cu2+, Fe2+, Mn2+, Mn3+, Fe3+, CrO42-, Si4+, and Hg+ ions on cytokines to predict dental metal allergy through a bioinformatics approach, in silico. Methods: Metal ion particles consisting of Cu2+, Fe2+, Mn2+, Mn3+, Fe3+, CrO42-, Si4+, and Hg+ were predicted to bind tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin (IL) IL-1b, IL-2, IL-4, IL-10, IL-13, IL-17, IL-23, and IL-33 act as target proteins were examined. Results: The blind docking simulation succeeded in identifying the comparison of the binding activity of metal ion particles on cytokines target proteins. The docking simulation results show that the metal ion with the most negative binding affinity value binds to the IL-17 protein. Conclusions: Metal ion particles consisting of Cu2+, Fe2+, Mn2+, Mn3+, Fe3+, CrO42-, Si4+, and Hg+ have the most negative binding affinity values for binding to IL-17 protein, which can cause allergic reactions predicted by molecular docking, in silico

Molecular docking of polyether ether ketone and nano-hydroxyapatite as biomaterial candidates for orthodontic mini-implant fabrication.

Context: Modified polyether ether ketone (PEEK) by adding nano-hydroxyapatite (HA) material on its fixture for mini-implant fabrication may increase resistance force through osseointegration. Aims: To analyze the binding molecular docking of PEEK incorporated with HA as a biomaterial candidate for orthodontic mini-implant fabrication through a bioinformatic approach, an in silico study. Methods: 3D ligand structure consisting of HA, PEEK and target proteins consisting of osteopontin, osteocalcin, osteonectin, bone morphogenetic protein 4 (BMP4), bone morphogenetic protein 2 (BMP2), bone morphogenetic protein 7 (BMP7), alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), Insulin growth factor-1 (IGF-1), osterix, tartrate-resistant acid phosphatase (TRAP), collagen alpha-1 (COL1A1) obtained from RCSB-PDB. It was analyzed the binding affinity of a single HA, PEEK, and HA + PEEK complex to twelve target proteins related to osseointegration. The types of chemical interactions produced by the ligands in the target protein domain consisted of Van der Waals, hydrogen, hydrophobic, pi, and alkyl. Results: The blind docking simulation succeeded in identifying the most negative binding affinity; it was found in the HA + PEEK molecular complex compared to HA and PEEK in the single condition. The type of chemical interaction formed consisted of hydrogen, van der Waals, pi, and alkyl. HA+PEEK showed the most negative binding affinity with ALP and IGF-1, as much as -8.7 binding affinity. Conclusions: The molecular docking of PEEK with HA exhibited a prominent binding affinity with osteogenic markers like ALP and IGF-1 in silico, allowing it to have a higher potential than nano-HA or PEEK as a single biomaterial for osseointegration as the fabrication of mini-implants that may support orthodontic treatment

An Insight of Proanthocyanidin and Polyamidoamine-Calcium Phosphate Nanoparticles as Biomaterial Candidate for Dentin regeneration in Dental Pulp Capping: A Narrative Review

Dental caries is the world's biggest dental problem with an incidence of 95%, causing tooth demineralization and complications including pulp perforation and premature tooth loss. A non-toxic biomaterial is required for increasing dentine regeneration in reversible dental caries. Proanthocyanidin (PA) is grape seed-derived flavonoid as antibacterial, anti-inflammatory, and antioxidant. However, PA provides low bioavailability so that it can be combined with polyamidoamine-calcium phosphate (PAMAM-CP) nanoparticles as drug delivery system. The investigation of PA and PAMAM-CP nanoparticles paste-based as innovation biomaterial for dental pulp capping may potential to induce dentine regeneration. The aim of this narrative review is to describe the combination of PA and PAMAM-CP nanoparticles as dental pulp capping biomaterial for dentin regeneration in dental caries. PA is able to express runt related transcription factor (Runx2), bone morphogenic protein-2 (BMP2), osteocalcin (OCN), and dentine sialophospoprotein (DSPP) which increase biomineralization and odontogenic differentiation. PAMAM is a macromolecule that provides attachment to dentine and induces remineralization. CP nanoparticles are calcium phosphate-based drug carriers that facilitate dentinal tubules penetration. PA loaded PAMAM-CP nanoparticles would be encapsulated releasing PA. PA suppresses Nuclear Factor-kB signaling pathway activation and decrease tumor necrosis factor-α so that inhibit dentinal matrix degradation. PA increases Runx2 and DSPP expression that manifest in dental pulp stem cells differentiation into odontoblasts. Combination of PA and PAMAM-CP nanoparticles may potential and beneficial as pulp capping biomaterial for dentin regeneration in dental caries

Basic Fibroblast Growth Factor Expression after Gingival Mesenchymal Stem Cell’s Metabolite Provision in Lipopolysaccharide induce inflammatory bone resorption in vivo

Normal bone is experience bone remodeling all the time where bone resorption and bone formation are balanced. Some chronic disease, such us periodontitis could affect the bone remodelling causing bone resorption is higher than bone formation. Basic Fibroblast Growth Factors (bFGF) has role on osteogenesis which can help in increasing bone formation. Gingival Mesenchymal Stem Cells’s Metabolite (GM SCM) is medical wasted products from Mesenchymal Stem Cells (MSC) which has various function. Aim of this study is to investigate the metabolites of GM SC effect on bFGF expression in inflammatory bone resorption caused by lipopolysaccharide. The 20 experimental animals were separated into four groups: control (C): 100 g PBS day 1-7, LPS group: 100 g LPS day 1-7, LPS+GM SCs' metabolite group: 100 g LPS + 100 g GM SCs' metabolite day 1-1-7, and GM SCs' metabolite group: 100 g M-GM SCs day 1-7. Escherichia Coli LPS was employed to trigger bone resorption on the calvaria of an animal model. The dose of GM SCs metabolite administered is 100 g once day through subcutaneous injection. Furthermore, on day 8, all samples were sacrificed by cervical dislocation. To count the number of bFGF positive expressions in osteoblast in the calvaria of animal models, bFGF monoclonal antibody and Diaminobenzidine (DAB) is added, resulting in a brown precipitate developing where the antibody has attached. The statistical analysis was performed to examine the significantly different between groups (p<0.05). The expression of bFGF was significantly decreased in LPS induced bone resorption group (LPS group), however, after GM SCs’ metabolite provision, bFGF expression was significantly elevated in GMSCs metabolite and LPS induced bone resorption (LPS+GM SCs’ metabolite group) with significantly different (p=0.0001; p<0.05). The positive expression of bFGF in osteoblast was elevated after GM SCs metabolite provision in LPS-induced calvaria bone resorption in wistar rats (R. novergicus) by means of immunohistochemistry examination

Gingival Mesenchymal Stem Cell Metabolite Decreasing TRAP, NFATc1, and Sclerotin Expression in LPS-Associated Inflammatory Osteolysis In Vivo

Objective Bone is a dynamic tissue that undergoes remodeling. During bone remodeling, there are transcription factors such as nuclear factor-activated T cells-1 (NFATc1), sclerostin, and tartrate-resistant acid phosphatase (TRAP) that are released for bone resorption. Metabolite from gingival mesenchymal stem cells (GMSCs) has the ability to activate proliferation, migration, immunomodulation, and tissue regeneration of bone cells and tissues. Furthermore, the aim of this study is to investigate the metabolite of GMSCs’ effect on expression of NFATc1, TRAP, and sclerostin in calvaria bone resorption of Wistar rats. Materials and Methods Twenty male healthy Wistar rats (Rattus norvegicus), 1 to 2 months old, 250 to 300 g body were divided into four groups, namely group 1 (G1): 100 µg phosphate-buffered saline day 1 to 7; group 2 (G2): 100 μg lipopolysaccharide (LPS) day 1 to 7; group 3 (G3): 100 μg LPS þ 100 μg GMSCs metabolite day 1 to 7; and group 4 (G4): 100 μg GMSCs metabolite day 1 to 7. Escherichia coli LPS was used to induce inflammatory osteolysis on the calvaria with subcutaneous injection. GMSCs metabolite was collected after passage 4 to 5, then injected subcutaneously on th

The Number of Osteoblast and Osteoclast during Orthodontic Tooth Movement after Preconditioned Gingiva Mesenchymal Stem Cell Allogeneic Transplantation in vivo

Malocclusion can affect the quality of life related to oral health. A novel technique to expedite orthodontic tooth movement (OTM) in order to minimize treatment length and the side effects. Under orthodontic fore, MSCs transplantation might hypothetically accelerate the bone remodeling process, resulting in OTM acceleration. To investigate the number of osteoclasts and osteoblasts in the tension side during OTM after transplantation of normoxic or hypoxic preconditioned allogeneic gingival mesenchymal stem cells in vivo. The OTM animal model was 48 male rabbits (Oryctolagus cuniculus) aged 6 months with body weight about 3-4 kg. There were 4 experimental groups in this study: control negative group (C-): injected with PBS without OTM, positive control group (C+): 50g OTM with 20µL PBS injection, treatment group 1 (T1): 50g OTM with 20µL GMSCs normoxia in PBS, treatment group 1 (T2): 50g OTM with 20µL GMSCs hypoxia in PBS. The injection was done in afflicted mandibular gingiva using µL small needle syringe with local infiltration technique. Every sample then was sacrificed after day 7, 14, and 28 respectively. The number of osteoblasts and osteoclasts in the alveolar bone during OTM was determined by hematoxylin and eosin staining. In T2 group, osteoblast was significantly enhanced on day 14 and 28 but not osteoclast number during OTM. There was significant different in osteoclast and osteoblast number between groups (p<0.05) GMSCs hypoxia preconditioned escalate osteoblast number but not decrease the osteoclast number in the tension side during orthodontic tooth movement in vivo