Background: Periodontitis is characterized by excessive osteoclastic activity, which is closely associated with inflammation. It is well established that MAPK/NF-kB axis is a key signaling pathway engaged in osteoclast differentiation. It is stated that that biphasic calcium phosphate (BCP) and platelet-rich fibrin (PRF) have significant antiostoeclastogenic effects in chronic periodontitis. Objective: We aimed to elucidate the synergetic effect of PRF/BCP involvement of the nuclear factor kappa–light–chain–enhancer of activated B cells (NF-kB) and the mitogen-activated protein kinase (MAPK) signaling pathway in osteoclast differentiation in chronic periodontitis. Methods: We induced osteoclast differentiation in vitro using peripheral blood mononuclear cells (PBMCs) derived from patients with chronic periodontitis. We assessed osteoclast generation by tartrate-resistant acid phosphatase (TRAP) activity, proinflammatory cytokines were investigated by ELISA and NF-κB, and IKB by immunoblot, respectively. MAPK proteins and osteoclast transcription factors were studied by Western blot analysis and osteoclast transcriptional genes were assessed by RT-PCR. Results: The results showed that the potent inhibitory effect of PRF/BCP on osteoclastogenesis was evidenced by decreased TRAP activity and the expression of transcription factors, NFATc1, c-Fos, and the osteoclast marker genes, TRAP, MMP-9, and cathepsin-K were found to be reduced. Further, the protective effect of PRF/BCP on inflammation-mediated osteoclastogenesis in chronic periodontitis was shown by decreased levels of proinflammatory cytokines, NF-kB, IKB, and MAPK proteins. Conclusions: PRF/BCP may promote a synergetic combination that could be used as a strong inhibitor of inflammation-induced osteoclastogenesis in chronic periodontitis.

Objectives: To qualitatively and quantitatively review the use of melatonin as a topical/systemic formulation for the management of periodontitis. Materials and methods: PubMed; Scopus; and Web of Science databases were searched using the MesH terms “melatonin” and “periodontitis”. Title and abstracts were screened to eliminate irrelevant and duplicate articles. The full text data of the screened articles were assessed using the selection criteria. Results: Of 176 identified articles (PubMed-66; Scopus-56; Web of Science-52; Cross-reference-2), only 12 studies qualified to be included in the systematic review. Four studies assessed the independent effect of 1% topical melatonin formulation while 8 articles assessed the adjunctive use of systemic melatonin formulation (1–10 mg) following scaling and root planing (SRP). All studies showed an improvement in periodontal parameters such as pocket depth, clinical attachment loss, periodontal disease index, community periodontal index, gingival bleeding scores, and prognostic marker levels in saliva and serum. A meta-analysis of data from 2 studies revealed that 1–2 mg (systemic) melatonin supplementation reduced pocket depth; although the difference was not statistically significant and hence cannot be interpreted or used for conclusive evidence. Risk of Bias Assessment tool (RoBANS) and Cochrane Collaboration RoB tool elicited a high risk of bias in the included studies. GRADE (recommendation assessment, development, and evaluation) inferred a weak recommendation for the use of melatonin in periodontitis management. Conclusions: Melatonin supplementation (topical and systemic) in periodontitis patients improved key periodontal parameters including pocket depth and clinical attachment loss. Clinical relevance: Melatonin could be a potential host modulatory agent for periodontitis management; although the data from the present review should be interpreted carefully due to the associated high risk of bias.

Mucormycosis is an infection caused by fungi belonging to the order Mucorales. Rhizopus oryzae is one of the most prevalent organisms identified in mucormycosis patients. Because it spreads quickly through the blood vessels, this opportunistic illness has an exceptionally high fatality rate, even when vigorous treatment is administered. Nonetheless, it has a high tolerance to antifungal medicines, limiting treatment options. As a result, improved methods for preventing and treating mucormycosis are desperately needed. Hence, this study was aimed at assessing the effect of lupeol, quercetin, and solasodine against mucormycosis based on computational approaches. The Rhizopus oryzae RNA-dependent RNA polymerase (RdRp) was the target for the design of drugs against the deadly mucormycosis. The three-dimensional structure of the RdRp was modelled with a Swiss model and validated using PROCHECK, VERIFY 3D, and QMEAN. Using the Schrodinger maestro module, a molecular docking study was performed between RdRp and the antimicrobial phytochemicals lupeol, quercetin, and solasodine. A molecular dynamics (MD) simulation study was used to assess the stability and interaction of the RdRp with these phytochemicals. The RdRp protein binds strongly to lupeol (-7.2 kcal/mol), quercetin (-9.1 kcal/mol), and solasodine (-9.6 kcal/mol), according to molecular docking assessment based on the lowest binding energy, confirmation, and bond interaction. Simulations suggest that lupeol, quercetin, and solasodine complexes with RdRp and showed stable confirmation with minimal fluctuation throughout the 200 nanoseconds based on the RMSD and RMSF trajectory assessments. The molecular docking and MD simulation investigation improved our understanding of phytochemical-RdRp interactions. Due to its high affinity for RdRp, solasodine may be a better treatment option for mucormycosis.

The secretome of the dental pulp mesenchymal stem cells (DPMSCS-S) have an array of regenerative potential and could aid in the rehabilitation of cancer patients post-therapeutic interventions, although caution is required as DPMSC-S have shown to augment prostate cancer cells. Thus, it is vital to assess if these pro-carcinogenic effects extend to other cancer types. To assess if DPMSC-S has any pro-carcinogenic effect on oral cancer, breast cancer, and melanoma cell lines. Conditioned media obtained from the isolated and characterized DPMSC (DPMSC-CM) were profiled using bead-based multiplex assay. AW13515 (oral cancer), MDA-MB-231 (breast cancer), and A-375 (melanoma) cell lines were exposed to 20%, 50%, and 100% DPMSC-CM for 24, 48, and 72 h. DPMSC-CM effect on the cancer cell properties and secretome were assessed. DPMSC-CM augmented invasion, adhesion, multi-drug resistance, DNA repair, and mitochondrial repair in AW13516 through upregulation of growth factors Ang-2, EGF, M−CSF, PDGF-AA, PDGF-BB, pro-inflammatory cytokines TNF-α, IL-2, downregulation of anti-inflammatory cytokine TGF-β1, and pro-inflammatory cytokine IL-4. In MDA-MB-231, invasion, and multi-drug resistance were augmented through upregulation of growth factors EGF, EPO, G-CSF, HGF, M−CSF, PDGF-AA, and pro-inflammatory cytokine TNF-α, CXCL10, IL-12p70. EMT, invasion, migration, and adhesion were augmented in A-375 through upregulation of growth factors Ang-2, EGF, PDGF-BB, TGF-α, pro-inflammatory cytokines TNF-α, and IL-17A. DPMSC-CM can augment the carcinogenic properties of oral cancer, breast cancer, and melanoma cells, further animal model studies are required to validate our in-vitro findings.

Periodontal disease is an infection-driven inflammatory disease characterized by the destruction of tooth-supporting tissues. The establishment of chronic inflammation will result in progressive destruction of bone and soft tissue changes. Severe periodontitis can lead to tooth loss. The disease has complex pathogenesis with an interplay between genetic, environmental, and host factors and pathogens. Effective management consists of plaque control and non-surgical interventions, along with adjuvant strategies to control inflammation and disrupt the pathogenic subgingival biofilms. Recent studies have examined novel approaches for managing periodontal diseases such as modulating microbial signaling mechanisms, tissue engineering, and molecular targeting of host inflammatory substances. Mounting evidence suggests the need to integrate omics-based approaches with traditional therapy to address the disease. This article discusses the various evolving and future drug targets, including proteomics, gene therapeutics, vaccines, and nanotechnology in personalized periodontal medicine for the effective management of periodontal diseases.