Reactive oxygen species are frequently associated with various cancers including pancreatic ductal adenocarcinomas (PDACs). Superoxide dismutase 2 (SOD2) is an enzyme that plays an important role in reactive oxygen species (ROS) signaling. Investigating the molecular function and biological functions of SOD2 can help us develop new therapeutic options and uncover new biomarkers for PDAC diagnosis and prognosis. Here, we show that nimbolide (NB), a triterpene limonoid, effectively blocks the growth and metastasis of PDACs by suppressing the expression and activity of SOD2. To identify the role of SOD2 in NB-induced anticancer activity, we used RNA interference to silence and plasmid transfection to overexpress it. Silencing SOD2 significantly reduced the growth and metastatic characteristics like epithelial-to-mesenchymal transition, invasion, migration, and colony-forming capabilities of PDACs, and NB treatment further reduced these characteristics. Conversely, the overexpression of SOD2 enhanced these metastatic characteristics. ROS signaling has a strong feedback mechanism with the PI3K/Akt signaling pathway, which could be mediated through SOD2. Finally, NB treatment to SOD2-overexpressing PDAC xenografts resulted in significant inhibition of tumor growth and metastasis. Overall, this work suggests that NB, a natural and safe phytochemical that silences SOD2 to induce high levels of ROS generation, results in increased apoptosis and reduced growth and progression of PDACs. The role of SOD2 in regulating NB-induced ROS generation presents itself as a therapeutic option for PDACs.

We sought to evaluate the effect of endodontic-causative microorganisms of primary infections on mononuclear cells such as CD14⁺, CD4⁺, CD8⁺, CD19⁺ and Tregs Foxp3⁺. Facultative anaerobic microorganisms were isolated from radicular conducts and peripheral blood samples, which were taken from patients with primary infections. Cellular cultures were performed with peripheral blood mononuclear cells (PBMC) with and without Actinomyces spp. and Streptococcus spp. during 48, 72, and 96 h of contact in culture (concentration 5 × 10⁵ cells/well) in a round plate bound with 48 wells. Later, PBMC was collected for analysis by flow cytometry, with the monoclonal antibodies αCD14, αCD4, αCD8, αCD19 and αFoxp3, and acquired using an FACSCanto II cytometer. The supernatant of cellular cultures was analyzed for the quantification of inflammatory cytokines. Data analysis was performed in FlowJo v10.8.2 and FCAPArray software, and statistical analysis was performed using GraphPad v5.0. software. We observed an increase in the percentage of CD14⁺ cells in patients at different hours of cellular culture in the presence of both Actinomyces spp. and Streptococcus spp. microorganisms, compared to healthy controls. This study demonstrates the role played by the innate immune system in the pathogeny of endodontic primary infections, explaining the effects that generate the more common microorganisms in this oral pathology.

Periapical lesions are common pathologies affecting the alveolar bone, often initiated by intraradicular lesions resulting from microbial exposure to dental pulp. These microorganisms trigger inflammatory and immune responses. When endodontic treatment fails to eliminate the infection, periapical lesions persist, leading to bone loss. The RANK/RANKL/OPG pathway plays a crucial role in both the formation and the destruction of the bone. In this study, the objective was to inhibit the RANK/RANKL pathway in vitro within exposed Thp-1 macrophages to endodontic microorganisms, specifically Enterococcus faecalis, which was isolated from root canals of 20 patients with endodontic secondary/persistent infection, symptomatic and asymptomatic, and utilizing an α-IRAK-4 inhibitor, we introduced endodontic microorganisms and/or lipoteichoic acid from Streptococcus spp. to cellular cultures in a culture plate, containing thp-1 cells and/or PBMC from patients with apical periodontitis. Subsequently, we assessed the percentages of RANK+, RANKL+, and OPG+ cells through flow cytometry and measured the levels of several inflammatory cytokines (IL-1β, TNF-α, IL-6, IL-8, IL-10, and IL-12p70) in the cellular culture supernatant through a CBA kit and performed analysis by flow cytometry. A significant difference was observed in the percentages of RANK+RANKL+, OPG+ RANKL+ cells in thp-1 cells and PBMCs from patients with apical periodontitis. The findings revealed significant differences in the percentages of the evaluated cells, highlighting the novel role of the IRAK-4 inhibitor in addressing this oral pathology, apical periodontitis, where bone destruction is observed.

Breast cancer rarely metastasizes to the parotid gland. Early recognition in patients with a history of malignancy is critical for timely diagnosis and treatment. We report the case of a 60-year-old female who presented with a two-month history of a left periauricular mass, 18 months after completing treatment for breast carcinoma. Despite the patient’s oncologic history, initial evaluation by our maxillofacial surgery service showed no evidence of distant metastasis, and we initially ruled out metastatic disease. Clinical evaluation, contrast-enhanced computed tomography (CT), fine-needle aspiration cytology (FNAC), PET-CT, and histopathological analysis were performed. Given the persistent and progressive nature of the mass, surgical excision was undertaken to obtain a definitive diagnosis and provide local control. Immunohistochemical analysis of the resected mass and adjacent node confirmed metastatic breast carcinoma infiltrating the parotid parenchyma and an intra-parotid lymph node, with strong positivity for progesterone receptor (PR) and carcinoembryonic antigen (CEA). Unfortunately, several months later, the patient developed pulmonary metastases and subsequently died.