Abstract
Bioactive molecule library screening may empirically identify effective combination therapies, but molecular mechanisms underlying favorable drug–drug interactions often remain unclear, ...precluding further rational design. In the absence of an accepted systems theory to interrogate synergistic responses, we introduce Omics-Based Interaction Framework (OBIF) to reveal molecular drivers of synergy through integration of statistical and biological interactions in synergistic biological responses. OBIF performs full factorial analysis of feature expression data from single versus dual exposures to identify molecular clusters that reveal synergy-mediating pathways, functions and regulators. As a practical demonstration, OBIF analyzed transcriptomic and proteomic data of a dyad of immunostimulatory molecules that induces synergistic protection against influenza A and revealed unanticipated NF-κB/AP-1 cooperation that is required for antiviral protection. To demonstrate generalizability, OBIF analyzed data from a diverse array of Omics platforms and experimental conditions, successfully identifying the molecular clusters driving their synergistic responses. Hence, unlike existing synergy quantification and prediction methods, OBIF is a phenotype-driven systems model that supports multiplatform interrogation of synergy mechanisms.
Obesity has been known to be a major risk factor for various types of cancers for several decades. More recently, the relationship between dysregulated adipokines and cancer development has been the ...focus of much research. Adipose tissue is an important endocrine organ that secretes adipokines that affect both autocrine and paracrine signaling. These adipokines modulate inflammation, induce insulin resistance, and regulate their own behavior and production.
Adipokine-production dysregulation is due to physiological changes in adipose tissue that prompt molecular modifications, including low-grade inflammation and the stimulatory production of reactive oxygen species. Additionally, studies have linked DNA damage response, genomic instability, and the innate immune response to tumorigenesis. Further investigation of adipokines and their role in the promotion of genomic instability may clarify the link between obesity and cancer, as well as elucidate potential pharmaceutical targets. In this review, we discuss the progress of recent literature, focusing on the impact of adipokines, genomic instability, and the innate immune response on increasing the risk of cancer.
Abstract
We present an interesting case of a young male with incidental finding of a mandibular ossifying fibroma. The patient sustained direct trauma to the mandible which prompted a computer ...tomography (CT) scan evaluation of the facial bones. The CT scan showed bilateral mandibular fractures with one of the fractures extending through an incidental finding of a 2.3 cm mandibular parasymphyseal lesion. The patient was previously asymptomatic without dental pain, jaw pain or swelling. This case is unique in the fact that the patient has an inherently rare tumor, was asymptomatic prior to his injury, demographically young for the presentation of this size tumor, and highlights the importance of a through trauma workup.
PDF
