Saliva is a fluid that can be collected easily and noninvasively. Its functions in the oral cavity are well known. Advances in molecular biology and technology, as well as research conducted by the various disciplines of omics (genomics, transcriptomics, proteomics, metabolomics, and metagenomics) have contributed to the identification and characterization of salivary components, including DNA, RNA, proteins, metabolites, and microorganisms. These biomolecules enter the saliva through extracellular and intracellular routes, providing information from several organs and systems and raising the possibility of their use as disease biomarkers. In recent years, these factors have expanded the potential use of saliva as a diagnostic fluid for oral and systemic diseases. This review integrates information regarding salivary biomolecules studied through omics and explores their utility as biomarkers for the diagnosis of several infectious and noninfectious diseases, and the opportunity they represent for the development of point of care devices for clinical application. We also discuss the advantages, disadvantages, and challenges to be overcome in order to establish saliva as a useful fluid for the accurate diagnosis and monitoring of a wide range of diseases.

The class A scavenger receptor (SR-A) binds modified lipoproteins and has been implicated in cholesterol ester deposition in macrophages. The SR-A also contributes to cellular adhesion. Using SR-A ^+/+ andSR-A ^{− / −} murine macrophages, we found SR-A expression important for both divalent cation-dependent and -independent adhesion of macrophages to the human smooth muscle cell extracellular matrix. The SR-A mediated 65 and 85% of macrophage adhesion to the extracellular matrix in the presence and absence of serum, respectively. When EDTA was added to chelate divalent cations, the SR-A mediated 90 and 95% of the macrophage adhesion without and with serum, respectively. SR-A-mediated adhesion to the extracellular matrix was prevented by fucoidin, an SR-A antagonist. Biglycan and decorin, proteoglycans of the extracellular matrix, were identified as SR-A ligands. Compared with control cells, Chinese hamster ovary cells expressing the SR-A showed 5- and 6-fold greater cell association (binding and internalization) of¹²⁵I-decorin and -biglycan, respectively. In competition studies, unlabeled proteoglycan or fucoidin competed for binding of¹²⁵I-labeled decorin and -biglycan, and biglycan and decorin competed for the SR-A-mediated cell association and degradation of ¹²⁵I-labeled acetylated LDL, a well characterized ligand for the SR-A. These results suggest that the SR-A could contribute to the adhesion of macrophages to the extracellular matrix of atherosclerotic plaques.

Upon activation, platelets secrete a 120-kDa protein that competes for the binding and internalization of acetyl low density lipoproteins (AcLDL) by macrophages. From the amino-terminal amino acid sequence, amino acid composition, and immunoblot analysis, we identified the active factor in platelet secretion products as sAPP, an alpha-secretase cleavage product of the beta-amyloid precursor protein (APP), that contains a Kunitz-type protease inhibitor (KPI) domain. We showed that both sAPP751 (also called Nexin II) and sAPP695, which does not contain a KPI domain, are ligands for the class A scavenger receptor (SR-A). Chinese hamster ovary cells stably transfected to express the SR-A bound and internalized 4-fold more human platelet-derived sAPP than control cells. The binding and internalization of sAPP were inhibited by the SR-A antagonist fucoidin. In addition, sAPP competed as effectively as fucoidin for SR-A-mediated cell association and degradation of (125)I-AcLDL. To determine if the KPI domain is required for the binding of sAPP to the SR-A, APP751 and APP695 were expressed in Chinese hamster ovary cells, and sAPP751 and sAPP695 purified from the medium were tested for their binding to the SR-A. sAPP751 and sAPP695 were equally effective in competing for the cell association of (125)I-AcLDL by SR-A-expressing cells, demonstrating that the KPI domain is not essential for binding. We also found that sAPP751 is present in extracts of atherosclerotic lesions and that sAPP competes for the SR-A-mediated cell association of oxidized low density lipoprotein. Deletion mutagenesis indicated that a negatively charged region of APP (residues 191-264) contributes to binding to the SR-A. These results suggest that the SR-A contributes to the clearance of sAPP and that sAPP competes for the cell association of other SR-A ligands.

Neuroglobin (Ngb), a protein located in the mammal’s brain, is involved in oxygen transport and free radical scavenging inside the neurons. Ngb colocalizes with choline acetyltransferase in the laterodorsal tegmental nucleus and in the pontine tegmental nucleus, both involved in the sleep–wake cycle regulation. Some studies have shown that free radicals accumulated during prolonged wakefulness are removed during sleep. Therefore, Ngb could act as a regulator of free radicals generated during prolonged wakefulness in the brain. The aim of this study was to determine whether prolonged wakefulness affects Ngb immunoreactivity because of increases in the oxidative stress induced by continuous neuronal activity. For this purpose, male adult Wistar rats were implanted with electrodes for sleep recordings and were divided into control and sleep-deprived groups. Sleep deprivation was carried out for 24 h by gentle handling of the animals. Sleep-wake activity was determined during the deprivation period or 24 h of control conditions. Subsequently, both groups of animals were killed and their brains were obtained and processed for Ngb immunohistochemical analysis and detection of lipid peroxidation. Our data found no evidence of increased oxidative stress in the brains of sleep-deprived animals compared with the controls. The number of Ngb-positive cells was decreased in the sleep-deprived animals in all analyzed areas of the brain compared with the control group. Our results suggest that Ngb could be involved in sleep regulation, independent of its role in the control of oxidative stress.