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Salivary glands are considered important targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Recent evidence suggests that along with angiotensin converting enzyme 2, certain cell surface sialic acids (Sia) may function as receptors for binding SARS-CoV-2 spike protein. Over 50 forms of Sia have been identified in nature, with N-acetylneuraminic acid (Neu5Ac) being the most abundant. We explored the Human Protein Atlas repository to analyze important enzymes in Neu5Ac biosynthesis and propose a hypothesis that further highlights the significance of salivary glands in coronavirus disease 19 (COVID-19). This work may facilitate research into targeted drug therapies for COVID-19. [ABSTRACT FROM AUTHOR]

With the advantages of convenient, painless and non-invasive collection, saliva holds great promise as a valuable biomarker source for cancer detection, pathological assessment and therapeutic monitoring. Salivary glycopatterns have shown significant potential for cancer screening in recent years. However, the understanding of benign lesions at non-cancerous sites in cancer diagnosis has been overlooked. Clarifying the influence of benign lesions on salivary glycopatterns and cancer screening is crucial for advancing the development of salivary glycopattern-based diagnostics. In this study, 2885 samples were analyzed using lectin microarrays to identify variations in salivary glycopatterns according to the number, location, and type of lesions. By utilizing our previously published data of tumor-associated salivary glycopatterns, the performance of machine learning algorithm for cancer screening was investigated to evaluate the effect of adding benign disease cases to the control group. The results demonstrated that both the location and number of lesions had discernible effects on salivary glycopatterns. And it was also revealed that incorporating a broad range of benign diseases into the controls improved the classifier's performance in distinguishing cancer cases from controls. This finding holds guiding significance for enhancing salivary glycopattern-based cancer screening and facilitates their practical implementation in clinical settings. [ABSTRACT FROM AUTHOR]

There is a high demand for a non-invasive, rapid, and highly accurate tool for disease diagnostics. Recently, saliva based diagnostics for the detection of specific biomarkers has drawn significant attention since the sample extraction is simple, cost-effective, and precise. Compared to blood, saliva contains a similar variety of DNA, RNA, proteins, metabolites, and microbiota that can be compiled into a multiplex of cancer detection markers. The salivary diagnostic method holds great potential for early-stage cancer diagnostics without any complicated and expensive procedures. Here, we review various cancer biomarkers in saliva and compare the biomarkers efficacy with traditional diagnostics and state-of-the-art bioelectronics. We summarize biomarkers in four major groups: genomics, transcriptomics, proteomics, and metabolomics/microbiota. Representative bioelectronic systems for each group are summarized based on various stages of a cancer. Systematic study of oxidative stress establishes the relationship between macromolecules and cancer biomarkers in saliva. We also introduce the most recent examples of salivary diagnostic electronics based on nanotechnologies that can offer rapid, yet highly accurate detection of biomarkers. A concluding section highlights areas of opportunity in the further development and applications of these technologies. [ABSTRACT FROM AUTHOR]

Storing saliva for nucleic acid diagnostics is problematic in resource-constrained settings. DNA Genotek's OMNIgene™ · DISCOVER kit aims to stabilise microbial DNA at room temperature. We evaluate this for long-term storage, determining DNA quantity/purity and human herpesvirus 8 (HHV-8) load as indicator. Viral loads and DNA degradation were assayed over 14 months in HHV-8–negative saliva spiked with cell-associated and cell-free virus and saliva collected fresh frozen and into kits from 10 HIV-positive patients. Viral loads remained constant for 6–9 months, yielding high quantities of DNA: subsequent losses were ≤48%. Patient samples, frozen or kit stored, produced pure DNA of comparable concentration. Higher HHV-8 detection in frozen saliva resulted from losses during ethanol precipitation using kits. After 14 months, DNA degradation was significant in frozen saliva, but that in kits had integrity similar to fresh samples. Storing frozen saliva is detrimental. This kit is well suited for collection, long-term storage, and assay of viral DNA in resource-constrained settings. [ABSTRACT FROM AUTHOR]

We present a microfluidic optoelectronic sensor for saliva diagnostics with a potential application for non-invasive early diagnosis of stomach cancer. Stomach cancer is the second most common cause of cancer-related deaths in the world. The primary identified cause is infection by a gram-negative bacterium Helicobacter pylori . These bacteria secrete the enzyme urease that converts urea into carbon dioxide (CO 2 ) and ammonia (NH 3 ), leading to their elevated levels in breath and body fluids. The proposed optoelectronic sensor will detect clinically relevant levels of CO 2 and NH 3 in saliva that can potentially be used for early diagnosis of stomach cancer. The sensor is composed of the embedded in a microfluidic device array of microwells filled with ion-exchange polymer microbeads doped with various organic dyes. The optical response of this unique highly diverse sensor is monitored over a broad spectrum, which provides a platform for cross-reactive sensitivity and allows detection of CO 2 and NH 3 in saliva at ppm levels. [ABSTRACT FROM AUTHOR]

Purpose: This article describes progress to date in the characterization of the salivary epigenome and considers the importance of previous work in the salivary microbiome, proteome, endocrine analytes, genome, and transcriptome. Methods: PubMed and Web of Science were used to extensively search the existing literature (original research and reviews) related to salivary diagnostics and biomarker development, of which 125 studies were examined. This article was derived from the most relevant 74 sources highlighting the recent state of the evolving field of salivary epigenomics and contributing significantly to the foundational work in saliva-based research. Findings: Validation of any new saliva-based diagnostic or analyte will require comparison to previously accepted standards established in blood. Careful attention to the collection, processing, and analysis of salivary analytes is critical for the development and implementation of newer applications that include genomic, transcriptomic, and epigenomic markers. All these factors must be integrated into initial study design. Implications: This commentary highlights the appeal of the salivary epigenome for translational applications and its utility in future studies of development and the interface among environment, disease, and health. [ABSTRACT FROM AUTHOR]

Objectives This study aims to create consensus concerning the use of a methodology by which the handling of saliva is standardized and quantitative detection of IL-8 and EGF in whole saliva is achieved. Our study involves evaluating the extent to which the pre-treatment of saliva samples with an anionic detergent - sodium dodecyl sulphate (SDS) - improved detection levels for IL-8 and EGF. Methods Whole saliva samples (n=28) were collected from healthy individuals and a protease inhibitor cocktail was added immediately. They were treated with either SDS or PBS for 20min and were then applied to a sandwich ELISA. Results and conclusions Saliva is a complex viscous fluid that requires degrading before the analysis of salivary biomarkers. We found that pre-treatment of samples with SDS significantly increased the detection levels for both EGF (293%) and IL-8 (346%) when compared with PBS-treated pairs (⁎⁎⁎P<0.001). According to the results we recommend: (i) pre-treatment of whole saliva samples with SDS for quantitative analysis (ii) using secretory output instead of concentration in the presentation of results to avoid individual variations and (iii) taking into consideration gender, age and meal intake since these have an impact on the secretory output of salivary proteins. [ABSTRACT FROM AUTHOR]

Abstract: Exosomes biomarkers mediating important biological process, especially in the systemic disease diagnostics and therapeutics, yet the protective exosomal vesicle structure hinders rapid, simple detection of the harbored molecules. We have established a new method, the electric field-induced release and measurement (EFIRM), which can simultaneously disrupt exosomes to release the contents and on-site monitoring the harbored exosomal RNA/proteins biomarkers. When exposed to a non-uniform electrical field, exosomal RNA and proteins are rapidly released. Bio-recognition of these biomolecules is carried out concurrently. We tested the hypothesis that the lung cancer cell line, H460 stably transfected with hCD63-GFP, would shed hCD63-GFP expressing exosomes that could be detected in serum and saliva. We confirmed in vivo that H460-CD63-GFP shed exosomes were transported to blood and saliva. This result demonstrates for the first time tumor-shed exosomes were detected in saliva, in addition to blood, presenting a new translational utility of exosome-based biomarker detection in saliva. [Copyright &y& Elsevier]

Abstract: Type II diabetes mellitus (T2DM) is one of the most common underdiagnosed metabolic diseases due to lack of recognizable symptoms in the early stage. T2DM can be largely prevented or controlled by diet or regular exercise at early stages, but often goes undetected for years, causing high rates of complications and mortality. Hence, a valid noninvasive early detection approach is urgently needed. In this study, we explored noninvasive detection of T2DM by salivary transcriptomic diagnostics. Salivary mRNA biomarkers were discovered by comparing microarray profiles of salivary transcriptomes in 13 T2DM patients and 13 healthy controls. The marker candidates selected from the microarray analysis were then subjected to verification in the original 26 samples using reverse transcription quantitative real-time polymerase chain reaction. Four up-regulated and two down-regulated mRNA biomarkers were validated. The logistic regression model showed that the combination of four identified biomarkers (KRAS, SAT1, EGFR, and PSMB2) could significantly distinguish T2DM patients from the healthy controls, yielding a receiver-operating characteristic-plot area-under-the-curve value of 0.917 with 100% sensitivity and 77% specificity. In conclusion, RNA signatures in saliva could serve as biomarkers for the detection of T2DM with high sensitivity and specificity, and offer a feasible means for early T2DM detection. [Copyright &y& Elsevier]

Summary: The translation of salivary alpha-amylase (sAA) to the ambulatory assessment of stress hinges on the development of technologies capable of speedy and accurate reporting of sAA levels. Here, we describe the developmental validation and usability testing of a point-of-care, colorimetric, sAA biosensor. A disposable test strip allows for streamlined sample collection and a corresponding hand-held reader with integrated analytic capabilities permits rapid analysis and reporting of sAA levels. Bioanalytical validation utilizing saliva samples from 20 normal subjects indicates that, within the biosensor''s linear range (10–230U/ml), its accuracy (R 2 =0.989), precision (CV<9%), and measurement repeatability (range −3.1% to +3.1%) approach more elaborate laboratory-based, clinical analyzers. The truncated sampling-reporting cycle (<1min) and the excellent performance characteristics of the biosensor has the potential to take sAA analysis out of the realm of dedicated, centralized laboratories and facilitate future sAA biomarker qualification studies. [Copyright &y& Elsevier]

Abstract: Recent developments in biosensor technology allow point-of-use reporting of salivary alpha amylase (sAA) levels while approaching the precision and accuracy of conventional laboratory-based testing. We deployed a portable prototype sAA biosensor in 54 healthy, male dental students during a low stress baseline and during final exams. At baseline, participants completed the Brief Symptom Inventory (BSI). At baseline and the exam week, participants provided saliva samples at 10 AM, 1 PM, and 5 PM, and rated concurrent subjective distress. Although subjective distress was higher during exams compared to baseline, sAA levels did not differ between baseline and exams. Higher sAA levels were related to higher concurrent subjective distress, and higher depressive and social isolation symptoms on the BSI were related to lower sAA during exams. Results from this study, in combination with previous validation data, suggest that the sAA biosensor is a promising tool for point-of-use measures of exposure to stress. [ABSTRACT FROM AUTHOR]

Summary: Early detection of oral squamous cell cancer (OSCC) is the key to improve the low 5-year survival rate. Using proteomic and genomic technologies we have previously discovered and validated salivary OSCC markers in American patients. The question arises whether these biomarkers are discriminatory in cohorts of different ethnic background. Six transcriptome (DUSP1, IL8, IL1B, OAZ1, SAT1, and S100P) and three proteome (IL1B, IL8, and M2BP) biomarkers were tested on 18 early and 17 late stage OSCC patients and 51 healthy controls with quantitative PCR and ELISA. Four transcriptome (IL8, IL1B, SAT1, and S100P) and all proteome biomarkers were significantly elevated (p <0.05) in OSCC patients. The combination of markers yielded an AUC of 0.86, 0.85 and 0.88 for OSCC total, T1–T2, and T3–T4, respectively. The sensitivity/specificity for OSCC total was 0.89/0.78, for T1–T2 0.67/0.96, and for T3–T4 0.82/0.84. In conclusion, seven of the nine salivary biomarkers (three proteins and four mRNAs) were validated and performed strongest in late stage cancer. Patient-based salivary diagnostics is a highly promising approach for OSCC detection. This study shows that previously discovered and validated salivary OSCC biomarkers are discriminatory and reproducible in a different ethnic cohort. These findings support the feasibility to implement multi-center, multi-ethnicity clinical trials towards the pivotal validation of salivary biomarkers for OSCC detection. [ABSTRACT FROM AUTHOR]

Abstract: The integration of semiconductor nanoparticle quantum dots (QDs) into a modular, microfluidic biosensor for the multiplexed quantitation of three important cancer markers, carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), and Her-2/Neu (C-erbB-2) was achieved. The functionality of the integrated sample processing, analyte capture and detection modalities was demonstrated using both serum and whole saliva specimens. Here, nano-bio-chips that employed a fluorescence transduction signal with QD-labeled detecting antibody were used in combination with antigen capture by a microporous agarose bead array supported within a microfluidics ensemble so as to complete the sandwich-type immunoassay. The utilization of QD probes in this miniaturized biosensor format resulted in signal amplification 30 times relative to that of standard molecular fluorophores as well as affording a reduction in observed limits of detection by nearly 2 orders of magnitude (0.02ng/mL CEA; 0.11pM CEA) relative to enzyme-linked immunosorbent assay (ELISA). Assay validation studies indicate that measurements by the nano-bio-chip system correlate to standard methods at R 2 =0.94 and R 2 =0.95 for saliva and serum, respectively. This integrated nano-bio-chip assay system, in tandem with next-generation fluorophores, promises to be a sensitive, multiplexed tool for important diagnostic and prognostic applications. [Copyright &y& Elsevier]