Dental pulp cells can differentiate toward an odontoblastic phenotype to produce reparative dentin beneath caries lesions. However, the mechanisms involved in pulp cell differentiation under pro-inflammatory stimuli have not been well-explored. Thus, we hypothesized that the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) could be a mediator involved in dental pulp cell differentiation toward an odontoblastic phenotype. We observed that TNF-α-challenged pulp cells exhibited increased mineralization and early and increased expression of dentin phosphoprotein (DPP), dentin sialoprotein (DSP), dentin matrix protein-1, and osteocalcin during a phase of reduced matrix metalloproteinase (MMP) expression. We investigated whether these events were related and found that p38, a mitogen-activated protein kinase, differentially regulated MMP-1 and DSP/DPP expression and mediated mineralization upon TNF-α treatment. These findings indicate that TNF-α stimulates differentiation of dental pulp cells toward an odontoblastic phenotype via p38, while negatively regulating MMP-1 expression.

Tityus serrulatus sting causes thousands of deaths annually worldwide. T. serrulatus-envenomed victims exhibit local or systemic reaction that culminates in pulmonary oedema, potentially leading to death. However, the molecular mechanisms underlying T. serrulatus venom (TsV) activity remain unknown. Here we show that TsV triggers NLRP3 inflammasome activation via K⁺ efflux. Mechanistically, TsV triggers lung-resident cells to release PGE₂, which induces IL-1β production via E prostanoid receptor 2/4-cAMP-PKA-NFκB-dependent mechanisms. IL-1β/IL-1R actions account for oedema and neutrophil recruitment to the lungs, leading to TsV-induced mortality. Inflammasome activation triggers LTB₄ production and further PGE₂ via IL-1β/IL-1R signalling. Activation of LTB₄-BLT1/2 pathway decreases cAMP generation, controlling TsV-induced inflammation. Exogenous administration confirms LTB₄ anti-inflammatory activity and abrogates TsV-induced mortality. These results suggest that the balance between LTB₄ and PGE₂ determines the amount of IL-1β inflammasome-dependent release and the outcome of envenomation. We suggest COX1/2 inhibition as an effective therapeutic intervention for scorpion envenomation.

OBJECTIVE: To review the prevalence of temporomandibular disorders (TMD) in children and adolescents, verifying the methodological variations. DATA SOURCES: Research conducted in Medline, PubMed, Lilacs and BBO databases, including manuscripts (except reviews and case reports) published from 1990 to 2012. The descriptors were "temporomandibular joint syndrome", "temporomandibular joint dysfunction syndrome", "temporomandibular joint disorders", "prevalence studies", and "cross-sectional studies"; the words "dysfunction", "disorder", "temporomandibular", "children", "adolescents", "prevalence", "frequency", and "transversal" were used. DATA SYNTHESIS: Seventeen articles were selected, and the TMD frequency varied from 16 to 68%. Regarding the methodological criteria, only three articles (18%) reported sample size determination, three (18%) clearly described the sample selection process by stratified selection technique, and nine studies (53%) carried out the calibration of the examiners. The diagnostic criteria used in the studies were: Helkimo index (n=2; 12%), Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) (n=4; 24%), the jaw index (n=1; 6%), clinical protocols (n=10; 59%), and anamnestic questionnaires (n=6; 35%). CONCLUSIONS: The TMD prevalence in children and adolescents varies in the literature. Appropriate and standardized methods are needed to identify, with greater validity, the presence of TMD in this population, allowing a better understanding of the pathological aspects in order to address more effective preventive and therapeutic procedures.