Saliva: diagnostics and therapeutic perspectives.
TL;DR: The avenue of saliva diagnostics incorporating transcriptomic, proteomic and metabolomic findings will enable us to connect salivary molecular analytes to monitor therapies, therapeutic outcomes, and finally disease progression in cancer.
Abstract: For the past two decades, salivary diagnostic approaches have been developed to monitor oral diseases such as periodontal diseases and to assess caries risk. Recently, the combination of emerging biotechnologies and salivary diagnostics has extended the range of saliva-based diagnostics from the oral cavity to the whole physiologic system as most compounds found in blood are also present in saliva. Accordingly, saliva can reflect the physiologic state of the body, including emotional, endocrinal, nutritional and metabolic variations and acts as a source for the monitoring of oral and also systemic health. This review presents an update on the status of saliva diagnostics and delves into their applications to the discovery of biomarkers for cancer detection and therapeutic applications. Translating scientific findings of nucleic acids, proteins and metabolites in body fluids to clinical applications is a cumbersome and challenging journey. Our research group is pursuing the biology of salivary analytes and the development of technologies for detection of distinct biomarkers with high sensitivity and specificity. The avenue of saliva diagnostics incorporating transcriptomic, proteomic and metabolomic findings will enable us to connect salivary molecular analytes to monitor therapies, therapeutic outcomes, and finally disease progression in cancer.
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TL;DR: Strategies for exosome isolation, the understanding to date of exosomes composition, functions, and pathways, and their potential for diagnostic and therapeutic applications are summarized.
1,639 citations
TL;DR: Saliva and its significance as a source of indicators for local, systemic, and infectious disorders is discussed and contemporary innovations and recent discoveries that deem saliva a mediator of the body's physiological condition are explored.
Abstract: SUMMARY The pursuit of timely, cost-effective, accurate, and noninvasive diagnostic methodologies is an endeavor of urgency among clinicians and scientists alike. Detecting pathologies at their earliest stages can significantly affect patient discomfort, prognosis, therapeutic intervention, survival rates, and recurrence. Diagnosis and monitoring often require painful invasive procedures such as biopsies and repeated blood draws, adding undue stress to an already unpleasant experience. The discovery of saliva-based microbial, immunologic, and molecular biomarkers offers unique opportunities to bypass these measures by utilizing oral fluids to evaluate the condition of both healthy and diseased individuals. Herewediscusssalivaanditssignificanceasasourceofindicators forlocal,systemic,andinfectiousdisorders.Wehighlightcontemporary innovations and explore recent discoveries that deem saliva a mediator of the body’s physiological condition. Additionally, we examine the current state of salivary diagnostics and its associated technologies, future aspirations, and potential as the preferred route of disease detection, monitoring, and prognosis.
450 citations
Cites background from "Saliva: diagnostics and therapeutic..."
...Although its proteomic content is estimated to be only 30% that of blood (99), saliva is actively being investigated as a rich source of protein biomarkers (100) capable of discerning healthy from diseased subjects (101)....
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TL;DR: Diagnostic value of saliva for 2019-nCoV, possibly direct invasion into oral tissues, and close contact transmission of 2019-NCoV by saliva droplets, expecting to contribute to 2019- nCoV epidemic control are summarized.
Abstract: 2019-nCoV epidemic was firstly reported at late December of 2019 and has caused a global outbreak of COVID-19 now. Saliva, a biofluid largely generated from salivary glands in oral cavity, has been reported 2019-nCoV nucleic acid positive. Besides lungs, salivary glands and tongue are possibly another hosts of 2019-nCoV due to expression of ACE2. Close contact or short-range transmission of infectious saliva droplets is a primary mode for 2019-nCoV to disseminate as claimed by WHO, while long-distance saliva aerosol transmission is highly environment dependent within indoor space with aerosol-generating procedures such as dental practice. So far, no direct evidence has been found that 2019-nCoV is vital in air flow for long time. Therefore, to prevent formation of infectious saliva droplets, to thoroughly disinfect indoor air and to block acquisition of saliva droplets could slow down 2019-nCoV dissemination. This review summarizes diagnostic value of saliva for 2019-nCoV, possibly direct invasion into oral tissues, and close contact transmission of 2019-nCoV by saliva droplets, expecting to contribute to 2019-nCoV epidemic control.
310 citations
TL;DR: An update on the current and future applications of saliva for diagnostic purposes, and a highlight on the emerging, newly developing technologies and tools for cancer screening, detection and monitoring.
Abstract: In this review, we provide an update on the current and future applications of saliva for diagnostic purposes. There are many advantages of using saliva as a biofluid. Its collection is fast, easy, inexpensive, and non-invasive. In addition, saliva, as a "mirror of the body," can reflect the physiological and pathological state of the body. Therefore, it serves as a diagnostic and monitoring tool in many fields of science such as medicine, dentistry, and pharmacotherapy. Introduced in 2008, the term "Salivaomics" aimed to highlight the rapid development of knowledge about various "omics" constituents of saliva, including: proteome, transcriptome, micro-RNA, metabolome, and microbiome. In the last few years, researchers have developed new technologies and validated a wide range of salivary biomarkers that will soon make the use of saliva a clinical reality. However, a great need still exists for convenient and accurate point-of-care devices that can serve as a non-invasive diagnostic tool. In addition, there is an urgent need to decipher the scientific rationale and mechanisms that convey systemic diseases to saliva. Another promising technology called liquid biopsy enables detection of circulating tumor cells (CTCs) and fragments of tumor DNA in saliva, thus enabling non-invasive early detection of various cancers. The newly developed technology-electric field-induced release and measurement (EFIRM) provides near perfect detection of actionable mutations in lung cancer patients. These recent advances widened the salivary diagnostic approach from the oral cavity to the whole physiological system, and thus point towards a promising future of salivary diagnostics for personalized individual medicine applications including clinical decisions and post-treatment outcome predictions. Impact statement The purpose of this mini-review is to make an update about the present and future applications of saliva as a diagnostic biofluid in many fields of science such as dentistry, medicine and pharmacotherapy. Using saliva as a fluid for diagnostic purposes would be a huge breakthrough for both patients and healthcare providers since saliva collection is easy, non-invasive and inexpensive. We will go through the current main diagnostic applications of saliva, and provide a highlight on the emerging, newly developing technologies and tools for cancer screening, detection and monitoring.
271 citations
Cites background from "Saliva: diagnostics and therapeutic..."
...Mature miRNA molecules cause down-regulation of gene expression.(47) They play an important role in cell growth, differentiation, apoptosis, stress and immune response or glucose secretion....
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...Currently, tumor-derived microvesicles (exosomes) are of high interest to researchers, as they might be the key to understanding the communication between cancer and the oral cavity, leading to the development of tumor-specific salivary biomarkers.(47) Using a rodent pancreatic cancer model, we have demonstrated that tumor-specific mRNA markers are shed from the pancreatic tumor cells, packaged in exosome and shuttled to salivary gland....
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TL;DR: The research strategies and analytical platforms commonly applied in the metabolomics studies are discussed and some limitations and further improvements which should be considered are discussed taking in mind potential applications of metabolomic research and practice.
229 citations
Cites background from "Saliva: diagnostics and therapeutic..."
...Saliva is produced ainly by three pairs of salivary glands (sublingual, submandibular nd parotid) and plays a crucial role in numerous physiologic funcions, like antibacterial and antiviral protection, as well as food wallowing [55,56]....
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...[55] N....
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...Many ompounds present in blood are also detected in saliva as their ransport from blood is proceeded by passive intracellular diffuion, active transport as well as extracellular ultrafiltration [55,59]....
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...However, he main advantage of saliva sample collection over blood specien is its noninvasiveness, easiness, speed and low cost [55–57]....
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References
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TL;DR: It is shown that exosomes contain both mRNA and microRNA, which can be delivered to another cell, and can be functional in this new location, and it is proposed that this RNA is called “exosomal shuttle RNA” (esRNA).
Abstract: Exosomes are vesicles of endocytic origin released by many cells. These vesicles can mediate communication between cells, facilitating processes such as antigen presentation. Here, we show that exosomes from a mouse and a human mast cell line (MC/9 and HMC-1, respectively), as well as primary bone marrow-derived mouse mast cells, contain RNA. Microarray assessments revealed the presence of mRNA from approximately 1300 genes, many of which are not present in the cytoplasm of the donor cell. In vitro translation proved that the exosome mRNAs were functional. Quality control RNA analysis of total RNA derived from exosomes also revealed presence of small RNAs, including microRNAs. The RNA from mast cell exosomes is transferable to other mouse and human mast cells. After transfer of mouse exosomal RNA to human mast cells, new mouse proteins were found in the recipient cells, indicating that transferred exosomal mRNA can be translated after entering another cell. In summary, we show that exosomes contain both mRNA and microRNA, which can be delivered to another cell, and can be functional in this new location. We propose that this RNA is called "exosomal shuttle RNA" (esRNA).
10,484 citations
TL;DR: A new, bead-based flow cytometric miRNA expression profiling method is used to present a systematic expression analysis of 217 mammalian miRNAs from 334 samples, including multiple human cancers, and finds the miRNA profiles are surprisingly informative, reflecting the developmental lineage and differentiation state of the tumours.
Abstract: Recent work has revealed the existence of a class of small non-coding RNA species, known as microRNAs (miRNAs), which have critical functions across various biological processes. Here we use a new, bead-based flow cytometric miRNA expression profiling method to present a systematic expression analysis of 217 mammalian miRNAs from 334 samples, including multiple human cancers. The miRNA profiles are surprisingly informative, reflecting the developmental lineage and differentiation state of the tumours. We observe a general downregulation of miRNAs in tumours compared with normal tissues. Furthermore, we were able to successfully classify poorly differentiated tumours using miRNA expression profiles, whereas messenger RNA profiles were highly inaccurate when applied to the same samples. These findings highlight the potential of miRNA profiling in cancer diagnosis.
9,470 citations
TL;DR: In the following, the first results on ultraviolet laser desorption (UVLD) of bioorganic compounds in the mass range above 10000 daltons are reported.
Abstract: In the following, the first results on ultraviolet laser desorption (UVLD) of bioorganic compounds in the mass range above 10000 daltons are reported. Strong molecular ion signals were registered by use of an organic matrix with strong absorption at the wavelength used for controlled energy deposition and soft desorption (7)
5,590 citations
TL;DR: Tumour-derived microvesicles may provide diagnostic information and aid in therapeutic decisions for cancer patients through a blood test by incorporating an mRNA for a reporter protein into them, and it is demonstrated that messages delivered by microvesicle are translated by recipient cells.
Abstract: Glioblastoma tumour cells release microvesicles (exosomes) containing mRNA, miRNA and angiogenic proteins. These microvesicles are taken up by normal host cells, such as brain microvascular endothelial cells. By incorporating an mRNA for a reporter protein into these microvesicles, we demonstrate that messages delivered by microvesicles are translated by recipient cells. These microvesicles are also enriched in angiogenic proteins and stimulate tubule formation by endothelial cells. Tumour-derived microvesicles therefore serve as a means of delivering genetic information and proteins to recipient cells in the tumour environment. Glioblastoma microvesicles also stimulated proliferation of a human glioma cell line, indicating a self-promoting aspect. Messenger RNA mutant/variants and miRNAs characteristic of gliomas could be detected in serum microvesicles of glioblastoma patients. The tumour-specific EGFRvIII was detected in serum microvesicles from 7 out of 25 glioblastoma patients. Thus, tumour-derived microvesicles may provide diagnostic information and aid in therapeutic decisions for cancer patients through a blood test.
4,118 citations
TL;DR: Using bioinformatics and cDNA cloning, this work found 15 new miRNA genes in C. elegans that express small transcripts that vary in abundance during larval development, and three of them have apparent homologs in mammals and/or insects.
Abstract: The lin-4 and let-7 antisense RNAs are temporal regulators that control the timing of developmental events in Caenorhabditis elegans by inhibiting translation of target mRNAs. let-7 RNA is conserved among bilaterian animals, suggesting that this class of small RNAs [microRNAs (miRNAs)] is evolutionarily ancient. Using bioinformatics and cDNA cloning, we found 15 new miRNA genes in C. elegans. Several of these genes express small transcripts that vary in abundance during C. elegans larval development, and three of them have apparent homologs in mammals and/or insects. Small noncoding RNAs of the miRNA class appear to be numerous and diverse.
3,062 citations