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Albagieh H, Alshehri AZ, Alduraywishi AS, Aldaws A, AlBalawi SS, Abu Shaqqaf HF, Almubayi RA. Evaluation of Salivary Diagnostics: Applications, Benefits, Challenges, and Future Prospects in Dental and Systemic Disease Detection. Cureus 2025; 17:e77520. [PMID: 39958008 PMCID: PMC11830415 DOI: 10.7759/cureus.77520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/15/2025] [Indexed: 02/18/2025] Open
Abstract
Saliva is a multifaceted biological fluid that plays a pivotal role in oral health and overall well-being. It is primarily produced by major salivary glands, with additional contributions from minor glands. Saliva is essential for various physiological functions, including oral lubrication, digestion, and defense against pathogens. Its intricate composition comprises proteins, electrolytes, enzymes, hormones, and microbial DNA, enabling it to act as a dynamic indicator of both local and systemic health. A literature search was conducted using PubMed, Web of Science, and Google Scholar to identify relevant studies published up to June 2024. The included studies involved human participants and provided original data or comprehensive reviews on salivary biomarkers. The findings indicate that salivary diagnostics show promise in diagnosing and monitoring systemic conditions such as diabetes and cardiovascular diseases, with salivary glucose levels correlating well with blood glucose levels. Biomarkers such as C-reactive protein (CRP) have been linked to cardiovascular risk, while saliva has been explored for cancer detection, including pancreatic and prostate cancers. Advances in techniques such as enzyme-linked immunosorbent assay (ELISA), saliva omics, and single-cell sequencing have furthered salivary diagnostics, providing insights into disease mechanisms. Additionally, quantitative mass spectrometry (qMS) and Raman spectroscopy (RS) contribute to non-invasive diagnostics for various conditions, including cancer. Collecting saliva samples from healthy individuals is crucial for early disease detection and evaluating treatment efficacy. This review underscores the growing importance of salivary tests in dental practice and their potential for diagnosing various health conditions. Further research is essential to address challenges related to variability and standardization. Dentists and healthcare professionals should consider incorporating salivary tests into clinical decision-making to enhance patient outcomes.
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Affiliation(s)
- Hamad Albagieh
- Dentistry, College of Dentistry, King Saud University, Riyadh, SAU
| | | | | | - Albandari Aldaws
- Dentistry, Princess Nourah Bint Abdulrahman University, Riyadh, SAU
| | | | | | - Reham A Almubayi
- Dentistry, Princess Nourah Bint Abdulrahman University, Riyadh, SAU
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Huang X, Bai S, Luo Y. Advances in research on biomarkers associated with acute myocardial infarction: A review. Medicine (Baltimore) 2024; 103:e37793. [PMID: 38608048 PMCID: PMC11018244 DOI: 10.1097/md.0000000000037793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Accepted: 03/14/2024] [Indexed: 04/14/2024] Open
Abstract
Acute myocardial infarction (AMI), the most severe cardiovascular event in clinical settings, imposes a significant burden with its annual increase in morbidity and mortality rates. However, it is noteworthy that mortality due to AMI in developed countries has experienced a decline, largely attributable to the advancements in medical interventions such as percutaneous coronary intervention. This trend highlights the importance of accurate diagnosis and effective treatment to preserve the myocardium at risk and improve patient outcomes. Conventional biomarkers such as myoglobin, creatine kinase isoenzymes, and troponin have been instrumental in the diagnosis of AMI. However, recent years have witnessed the emergence of new biomarkers demonstrating the potential to further enhance the accuracy of AMI diagnosis. This literature review focuses on the recent advancements in biomarker research in the context of AMI diagnosis.
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Affiliation(s)
| | - Suwen Bai
- Central Laboratory, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People’s Hospital of Shenzhen, Shenzhen, China
| | - Yumei Luo
- Guangdong Medical University, Zhanjiang, China
- Cardiology Department of The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People’s Hospital of Shenzhen, Shenzhen, China
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LaCasse Z, Chivte P, Kress K, Seethi VDR, Bland J, Alhoori H, Kadkol SS, Gaillard ER. Enhancing saliva diagnostics: The impact of amylase depletion on MALDI-ToF MS profiles as applied to COVID-19. J Mass Spectrom Adv Clin Lab 2024; 31:59-71. [PMID: 38323116 PMCID: PMC10846328 DOI: 10.1016/j.jmsacl.2024.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Revised: 12/19/2023] [Accepted: 01/19/2024] [Indexed: 02/08/2024] Open
Abstract
Introduction Human saliva contains a wealth of proteins that can be monitored for disease diagnosis and progression. Saliva, which is easy to collect, has been extensively studied for the diagnosis of numerous systemic and infectious diseases. However, the presence of amylase, the most abundant protein in saliva, can obscure the detection of low-abundance proteins by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-ToF MS), thus reducing its diagnostic utility. Objectives In this study, we used a device to deplete salivary amylase from water-gargle samples by affinity adsorption. Following depletion, saliva proteome profiling was performed using MALDI-ToF MS on gargle samples from individuals confirmed to have COVID-19 based on nasopharyngeal (NP) swab reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results The depletion of amylase led to increased signal intensities of various peaks and the detection of previously unobserved peaks in the MALDI-ToF MS spectra. The overall specificity and sensitivity after amylase depletion were 100% and 85.17%, respectively, for detecting COVID-19. Conclusion This simple, rapid, and inexpensive technique for depleting salivary amylase can reveal spectral diversity in saliva using MALDI-ToF MS, expose low-abundance proteins, and assist in establishing novel biomarkers for diseases.
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Affiliation(s)
- Zane LaCasse
- Departments of Chemistry and Biochemistry, Northern Illinois University, DeKalb, IL 60115, USA
| | - Prajkta Chivte
- Departments of Chemistry and Biochemistry, Northern Illinois University, DeKalb, IL 60115, USA
| | - Kari Kress
- Departments of Chemistry and Biochemistry, Northern Illinois University, DeKalb, IL 60115, USA
- Thermo Fisher Scientific, Rockford, IL 61101, USA
| | | | - Joshua Bland
- Department of Pathology, University of Illinois at Chicago, Chicago, IL 60612, USA
| | - Hamed Alhoori
- Departments of Computer Science, Northern Illinois University, DeKalb, IL 60115, USA
| | - Shrihari S. Kadkol
- Department of Pathology, University of Illinois at Chicago, Chicago, IL 60612, USA
| | - Elizabeth R. Gaillard
- Departments of Chemistry and Biochemistry, Northern Illinois University, DeKalb, IL 60115, USA
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Shen M, Li Z, Li H, Yan X, Feng B, Xu L. Association of periodontitis and tooth loss with extent of coronary atherosclerosis in patients with type 2 diabetes mellitus. Front Endocrinol (Lausanne) 2023; 14:1243992. [PMID: 38075042 PMCID: PMC10702216 DOI: 10.3389/fendo.2023.1243992] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Accepted: 11/06/2023] [Indexed: 12/18/2023] Open
Abstract
Aim The objective was to investigate the association of periodontitis and tooth loss with extent of diabetic coronary atherosclerosis. Materials and methods 272 patients who were hospitalized at Shanghai East hospital and underwent a coronary artery calcium (CAC) CT scan were enrolled in this study. Individuals were grouped based on their CAC scores into a normal-to-mild coronary atherosclerosis (AS) group (0 ≤ score ≤ 100, n=184) and a moderate-to-severe group (score≥101, n=88). Periodontitis parameters and number of missing teeth were evaluated for every patient. The severity of periodontitis was categorized as mild, moderate, or severe. The taxonomic composition of the microbiota was determined using full-length 16S ribosomal RNA gene sequencing. Salivary inflammatory factors were tested by ELISA. Results Clinical attachment loss (CAL) (P =0.05) and the number of teeth lost (P = 0.016) were significantly higher in the moderate-to-severe coronary AS group, with these differences being more obvious in younger patients and patients with short-duration diabetes. Multivariate logistic regression analysis revealed that CAL (OR = 1.231, 95% CI = 1.066-1.214, P = 0.047) and having 10-19 missing teeth (OR = 1.604, 95% CI = 1.393-6.555, P = 0.05) were strongly associated with the presence of moderate-to-severe coronary AS. Salivary IL-6 and TNF-α levels, as well as levels of Porphyromonas gingivalis and Neisseria mucosa, were significantly elevated in the moderate-to-severe coronary AS group. Conclusion It was found that both tooth loss and CAL were related to the extent of diabetic coronary AS. Saliva inflammatory factors and oral bacteremia may be new biomarkers for moderate-to-severe coronary AS.
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Affiliation(s)
- Minhua Shen
- Department of Stomatology, East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Zhen Li
- Department of Stomatology, East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Huizhi Li
- Department of Endocrinology, East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xinfeng Yan
- Department of Endocrinology, East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Bo Feng
- Department of Endocrinology, East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Lei Xu
- Department of Endocrinology, East Hospital, Tongji University School of Medicine, Shanghai, China
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Botía M, Ortín-Bustillo A, López-Martínez MJ, Fuentes P, Escribano D, González-Bulnes A, Manzanilla EG, Martínez-Subiela S, Tvarijonaviciute A, López-Arjona M, Cerón JJ, Tecles F, Muñoz-Prieto A. Gaining knowledge about biomarkers of the immune system and inflammation in the saliva of pigs: The case of myeloperoxidase, S100A12, and ITIH4. Res Vet Sci 2023; 164:104997. [PMID: 37657394 DOI: 10.1016/j.rvsc.2023.104997] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 08/07/2023] [Accepted: 08/23/2023] [Indexed: 09/03/2023]
Abstract
An assay for the measurement of myeloperoxidase (Mpx) in porcine saliva was developed and validated, and factors influencing Mpx and another two biomarkers of inflammation and immune system, the protein S100A12 and the inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4), were studied. The spectrophotometric method for Mpx measurement validated in this assay showed an adequate analytical performance including precision and accuracy. When a group of twenty healthy pigs was sampled every 4 h from 8 a.m. until 8 p.m., Mpx and S100A12 showed significant increases at 4 p.m., whereas ITIH4 concentration showed a significant decrease at 12 a.m. Increases were also seen in salivary Mpx, S100A12, and ITIH4 levels 24 h after the intramuscular administration of Escherichia coli lipopolysaccharide in five pigs; whereas in a non-septic inflammation after the subcutaneous administration of turpentine oil to five pigs changes were seen in S100A12 at 3 h and in ITIH4 at 48 h. When a stressful situation consisting of the transportation and stay of 4 h to a slaughterhouse of 24 pigs was performed, all analytes were increased after 4 h of lairage in the slaughterhouse compared with the values that were obtained the day before at the same time of the day. Mpx can be measured in the saliva of pigs with the automated assay described in this report. Mpx, S100A12, and ITIH4 salivary levels can change depending on the hour of the day in which the sample is taken, and increases can be produced due to sepsis, non-septic inflammation and stress.
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Affiliation(s)
- María Botía
- Interdisciplinary Laboratory of Clinical Analysis (Interlab-UMU), Veterinary School, Regional Campus of International Excellence 'Campus Mare Nostrum', University of Murcia, Campus de Espinardo s/n, 30100, Espinardo, Murcia, Spain
| | - Alba Ortín-Bustillo
- Interdisciplinary Laboratory of Clinical Analysis (Interlab-UMU), Veterinary School, Regional Campus of International Excellence 'Campus Mare Nostrum', University of Murcia, Campus de Espinardo s/n, 30100, Espinardo, Murcia, Spain
| | - María J López-Martínez
- Interdisciplinary Laboratory of Clinical Analysis (Interlab-UMU), Veterinary School, Regional Campus of International Excellence 'Campus Mare Nostrum', University of Murcia, Campus de Espinardo s/n, 30100, Espinardo, Murcia, Spain
| | | | - Damián Escribano
- Interdisciplinary Laboratory of Clinical Analysis (Interlab-UMU), Veterinary School, Regional Campus of International Excellence 'Campus Mare Nostrum', University of Murcia, Campus de Espinardo s/n, 30100, Espinardo, Murcia, Spain; Department of Animal Production, Regional Campus of International Excellence 'Campus Mare Nostrum', University of Murcia, Campus de Espinardo s/n, 30100, Espinardo, Murcia, Spain
| | - Antonio González-Bulnes
- Departamento de Producción y Sanidad Animal, Facultad de Veterinaria, Universidad Cardenal Herrera-CEU, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115, Valencia, Spain
| | - Edgar G Manzanilla
- Pig Development Department, The Irish Food and Agriculture Authority, Teagasc, Moorepark, P61 C996, Fermoy, Co Cork, Ireland; School of Veterinary Medicine, University College Dublin, Dublin 4, Ireland
| | - Silvia Martínez-Subiela
- Interdisciplinary Laboratory of Clinical Analysis (Interlab-UMU), Veterinary School, Regional Campus of International Excellence 'Campus Mare Nostrum', University of Murcia, Campus de Espinardo s/n, 30100, Espinardo, Murcia, Spain
| | - Asta Tvarijonaviciute
- Interdisciplinary Laboratory of Clinical Analysis (Interlab-UMU), Veterinary School, Regional Campus of International Excellence 'Campus Mare Nostrum', University of Murcia, Campus de Espinardo s/n, 30100, Espinardo, Murcia, Spain
| | - Marina López-Arjona
- Department of Animal and Food Science, Universitat Autònoma de Barcelona, Cerdanyola de Vallés, 08193 Barcelona, Spain
| | - José J Cerón
- Interdisciplinary Laboratory of Clinical Analysis (Interlab-UMU), Veterinary School, Regional Campus of International Excellence 'Campus Mare Nostrum', University of Murcia, Campus de Espinardo s/n, 30100, Espinardo, Murcia, Spain
| | - Fernando Tecles
- Interdisciplinary Laboratory of Clinical Analysis (Interlab-UMU), Veterinary School, Regional Campus of International Excellence 'Campus Mare Nostrum', University of Murcia, Campus de Espinardo s/n, 30100, Espinardo, Murcia, Spain.
| | - Alberto Muñoz-Prieto
- Interdisciplinary Laboratory of Clinical Analysis (Interlab-UMU), Veterinary School, Regional Campus of International Excellence 'Campus Mare Nostrum', University of Murcia, Campus de Espinardo s/n, 30100, Espinardo, Murcia, Spain
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Rammos A, Bechlioulis A, Kalogeras P, Watson CJ, Salvo P, Lomonaco T, Kardakari O, Tripoliti EE, Goletsis Y, Fotiadis DI, Katsouras CS, Michalis LK, Naka KK. The Potential Role of Salivary NT-proBNP in Heart Failure. Life (Basel) 2023; 13:1818. [PMID: 37763222 PMCID: PMC10532738 DOI: 10.3390/life13091818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Revised: 08/20/2023] [Accepted: 08/23/2023] [Indexed: 09/29/2023] Open
Abstract
BACKGROUND Serum natriuretic peptides (NPs) have an established role in heart failure (HF) diagnosis. Saliva NT-proBNP that may be easily acquired has been studied little. METHODS Ninety-nine subjects were enrolled; thirty-six obese or hypertensive with dyspnoea but no echocardiographic HF findings or raised NPs served as controls, thirteen chronic HF (CHF) patients and fifty patients with acute decompensated HF (ADHF) requiring hospital admission. Electrocardiogram, echocardiogram, 6 min walking distance (6MWD), blood and saliva samples, were acquired in all participants. RESULTS Serum NT-proBNP ranged from 60-9000 pg/mL and saliva NT-proBNP from 0.64-93.32 pg/mL. Serum NT-proBNP was significantly higher in ADHF compared to CHF (p = 0.007) and in CHF compared to controls (p < 0.05). There was no significant difference in saliva values between ADHF and CHF, or between CHF and controls. Saliva and serum levels were positively associated only in ADHF patients (R = 0.352, p = 0.012). Serum NT-proBNP was positively associated with NYHA class (R = 0.506, p < 0.001) and inversely with 6MWD (R = -0.401, p = 0.004) in ADHF. Saliva NT-proBNP only correlated with age in ADHF patients. CONCLUSIONS In the current study, saliva NT-proBNP correlated with serum values in ADHF patients, but could not discriminate between HF and other causes of dyspnoea. Further research is needed to explore the value of saliva NT-proBNP.
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Affiliation(s)
- Aidonis Rammos
- 2nd Department of Cardiology, Faculty of Medicine, School of Health Sciences, University of Ioannina & University Hospital of Ioannina, 45110 Ioannina, Greece (P.K.); (O.K.)
| | - Aris Bechlioulis
- 2nd Department of Cardiology, Faculty of Medicine, School of Health Sciences, University of Ioannina & University Hospital of Ioannina, 45110 Ioannina, Greece (P.K.); (O.K.)
| | - Petros Kalogeras
- 2nd Department of Cardiology, Faculty of Medicine, School of Health Sciences, University of Ioannina & University Hospital of Ioannina, 45110 Ioannina, Greece (P.K.); (O.K.)
| | - Chris J. Watson
- Wellcome-Wolfson Institute for Experimental Medicine, Queen’s University Belfast, Belfast BT9 7BL, UK;
- UCD Conway Institute, School of Medicine, University College Dublin, 4 Dublin, Ireland
| | - Pietro Salvo
- Institute of Clinical Physiology, Italian National Research Council, Via G. Moruzzi 1, 56124 Pisa, Italy
| | - Tommaso Lomonaco
- Department of Chemistry and Industrial Chemistry, University of Pisa, 56124 Pisa, Italy;
| | - Olga Kardakari
- 2nd Department of Cardiology, Faculty of Medicine, School of Health Sciences, University of Ioannina & University Hospital of Ioannina, 45110 Ioannina, Greece (P.K.); (O.K.)
| | - Evanthia E. Tripoliti
- Department of Biomedical Research, Institute of Molecular Biology and Biotechnology, FORTH, 45110 Ioannina, Greece (Y.G.); (D.I.F.)
| | - Yorgos Goletsis
- Department of Biomedical Research, Institute of Molecular Biology and Biotechnology, FORTH, 45110 Ioannina, Greece (Y.G.); (D.I.F.)
- Department of Economics, University of Ioannina, 45110 Ioannina, Greece
| | - Dimitris I. Fotiadis
- Department of Biomedical Research, Institute of Molecular Biology and Biotechnology, FORTH, 45110 Ioannina, Greece (Y.G.); (D.I.F.)
- Department of Economics, University of Ioannina, 45110 Ioannina, Greece
- Unit of Medical Technology and Intelligent Information Systems, University of Ioannina, 45110 Ioannina, Greece
| | - Christos S. Katsouras
- 2nd Department of Cardiology, Faculty of Medicine, School of Health Sciences, University of Ioannina & University Hospital of Ioannina, 45110 Ioannina, Greece (P.K.); (O.K.)
| | - Lampros K. Michalis
- 2nd Department of Cardiology, Faculty of Medicine, School of Health Sciences, University of Ioannina & University Hospital of Ioannina, 45110 Ioannina, Greece (P.K.); (O.K.)
| | - Katerina K. Naka
- 2nd Department of Cardiology, Faculty of Medicine, School of Health Sciences, University of Ioannina & University Hospital of Ioannina, 45110 Ioannina, Greece (P.K.); (O.K.)
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Kelotte D, Melath A, Kaykool S, Chandran N. Nanotechnology and periodontics. J Periodontal Implant Sci 2023; 53:245-247. [PMID: 37635654 PMCID: PMC10465811 DOI: 10.5051/jpis.235304edi01] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Accepted: 08/04/2023] [Indexed: 08/29/2023] Open
Affiliation(s)
- Deepith Kelotte
- Department of Periodontics, Mahe Institute of Dental Sciences and Hospital, Puducherry, India.
| | - Anil Melath
- Department of Periodontics, Mahe Institute of Dental Sciences and Hospital, Puducherry, India
| | - Subair Kaykool
- Department of Periodontics, Mahe Institute of Dental Sciences and Hospital, Puducherry, India
| | - Nanditha Chandran
- Department of Periodontics, Mahe Institute of Dental Sciences and Hospital, Puducherry, India
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Westreich R, Tsaban G, Neumann Y, Abu Salman A, Braver O, Braiman D, Zamed T, Neuhaus ZF, Deutsch O, Palmon A, Maimon N, Zahger D, Abramowitz Y. Development of saliva-based cardiac troponin I point-of-care test using alpha-amylase depletion: a feasibility study. Coron Artery Dis 2023; 34:351-355. [PMID: 37335230 DOI: 10.1097/mca.0000000000001257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/21/2023]
Abstract
INTRODUCTION Cardiac troponin (cTn) is the biomarker of choice for detection of myocardial injury. There is a great need for simple point-of-care (POC) troponin testing among patients with chest pain, mainly in the prehospital setting. The purpose of this study was to evaluate the presence of cardiac troponin I (cTnI) in saliva of patients with myocardial injury using alpha-amylase depletion technique. METHODS Saliva samples were collected from 40 patients with myocardial injury who were tested positive for conventional high-sensitivity cardiac troponin T (cTnT) blood tests, and from 66 healthy volunteers. Saliva samples were treated for the removal of salivary alpha-amylase. Treated and untreated samples were tested with blood cTnI Rapid Diagnostic Test. Salivary cTnI levels were compared to blood cTnT levels. RESULTS Thirty-six of 40 patients with positive blood cTnT had positive salivary samples for cTnI following alpha-amylase depletion treatment (90.00% sensitivity). Moreover, three of the four negative saliva samples were obtained from patients with relatively low blood cTnT levels of 100 ng/L or less (96.88% sensitivity for 100 ng/L and above). The negative predictive value was 93.65% and rose up to 98.33% considering the 100 ng/L cutoff. Positive predictive values were 83.72% and 81.58%, respectively. Among 66 healthy volunteers and 7 samples yielded positive results (89.39% specificity). CONCLUSION In this preliminary work, the presence of cTnI in saliva was demonstrated for the first time to be feasibly identified by a POC oriented assay. The specific salivary alpha-amylase depletion technique was shown to be crucial for the suggested assay.
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Affiliation(s)
- Roi Westreich
- Department of Cardiology, Soroka University Medical Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva
| | - Gal Tsaban
- Department of Cardiology, Soroka University Medical Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva
| | - Yoav Neumann
- Department of D&R, Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel
| | - Amjad Abu Salman
- Department of Cardiology, Soroka University Medical Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva
| | - Omri Braver
- Department of Cardiology, Soroka University Medical Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva
| | - Dana Braiman
- Department of Cardiology, Soroka University Medical Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva
| | - Tali Zamed
- Department of Cardiology, Soroka University Medical Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva
| | - Zipora Feiga Neuhaus
- Department of Cardiology, Soroka University Medical Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva
| | - Omer Deutsch
- Department of D&R, Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel
| | - Aaron Palmon
- Department of D&R, Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel
| | - Nimrod Maimon
- Department of Cardiology, Soroka University Medical Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva
| | - Doron Zahger
- Department of Cardiology, Soroka University Medical Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva
| | - Yigal Abramowitz
- Department of Cardiology, Soroka University Medical Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva
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Nijakowski K, Jankowski J, Gruszczyński D, Surdacka A. Salivary Alterations of Myeloperoxidase in Patients with Systemic Diseases: A Systematic Review. Int J Mol Sci 2023; 24:12078. [PMID: 37569455 PMCID: PMC10418962 DOI: 10.3390/ijms241512078] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 07/22/2023] [Accepted: 07/26/2023] [Indexed: 08/13/2023] Open
Abstract
Salivary myeloperoxidase (MPO) is a key mediator of the oral immune system, acting as an enzyme that utilises H2O2 to generate molecules with high bactericidal activity. While MPO determination in plasma is quite common, the use of saliva is still rare. Our systematic review was designed to answer the question "Are salivary levels of myeloperoxidase altered in patients with systemic diseases?". Following the inclusion and exclusion criteria, we included twenty-six studies. Altered MPO levels in saliva were most commonly found in patients with cardiovascular and gastrointestinal diseases. Most studies concerned unstimulated whole saliva, and only a few of them stimulated, mainly by chewing paraffin. Enzyme-linked immunosorbent assay (ELISA) was the most common method for determination of MPO concentrations in saliva. Increased salivary MPO levels were more often observed for inflammatory diseases, except patients with inflammatory bowel diseases who were eligible for biologic therapy. In conclusion, MPO could be altered in the saliva of patients with systematic diseases, especially cardiovascular or gastrointestinal diseases. However, further investigations are recommended to validate these outcomes.
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Affiliation(s)
- Kacper Nijakowski
- Department of Conservative Dentistry and Endodontics, Poznan University of Medical Sciences, 60-812 Poznan, Poland;
| | - Jakub Jankowski
- Student’s Scientific Group in Department of Conservative Dentistry and Endodontics, Poznan University of Medical Sciences, 60-812 Poznan, Poland; (J.J.); (D.G.)
| | - Dawid Gruszczyński
- Student’s Scientific Group in Department of Conservative Dentistry and Endodontics, Poznan University of Medical Sciences, 60-812 Poznan, Poland; (J.J.); (D.G.)
| | - Anna Surdacka
- Department of Conservative Dentistry and Endodontics, Poznan University of Medical Sciences, 60-812 Poznan, Poland;
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Huang Z, Yang X, Huang Y, Tang Z, Chen Y, Liu H, Huang M, Qing L, Li L, Wang Q, Jie Z, Jin X, Jia B. Saliva - a new opportunity for fluid biopsy. Clin Chem Lab Med 2023; 61:4-32. [PMID: 36285724 DOI: 10.1515/cclm-2022-0793] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Accepted: 09/29/2022] [Indexed: 12/15/2022]
Abstract
Saliva is a complex biological fluid with a variety of biomolecules, such as DNA, RNA, proteins, metabolites and microbiota, which can be used for the screening and diagnosis of many diseases. In addition, saliva has the characteristics of simple collection, non-invasive and convenient storage, which gives it the potential to replace blood as a new main body of fluid biopsy, and it is an excellent biological diagnostic fluid. This review integrates recent studies and summarizes the research contents of salivaomics and the research progress of saliva in early diagnosis of oral and systemic diseases. This review aims to explore the value and prospect of saliva diagnosis in clinical application.
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Affiliation(s)
- Zhijie Huang
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Xiaoxia Yang
- Department of Endodontics, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Yisheng Huang
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Zhengming Tang
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Yuanxin Chen
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Hongyu Liu
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Mingshu Huang
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Ling Qing
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Li Li
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Qin Wang
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Zhuye Jie
- BGI Genomics, BGI-Shenzhen, Shenzhen, P.R. China
- Shenzhen Key Laboratory of Human Commensal Microorganisms and Health Research, BGI-Shenzhen, Shenzhen, P.R. China
- Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark
| | - Xin Jin
- BGI Genomics, BGI-Shenzhen, Shenzhen, P.R. China
- School of Medicine, South China University of Technology, Guangzhou, P.R. China
| | - Bo Jia
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
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11
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Domenico T, Rita A, Giacomo S, Diego A, Thelma P, Mariana G, Giampaolo N, Francesco N, Maria G, Francesco F, Bruno B, Marco M, Diana C. Salivary biomarkers for diagnosis of acute myocardial infarction: A systematic review. Int J Cardiol 2023; 371:54-64. [PMID: 36167219 DOI: 10.1016/j.ijcard.2022.09.043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 09/11/2022] [Accepted: 09/20/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND Acute myocardial infarction (AMI) accounts for about 7 million deaths per year worldwide. The early identification of signs and symptoms and the detection of specific serological markers of this disease are mandatory to reach a prompt diagnosis and begin potentially life-saving treatment. Point-of-care technologies applied to salivary diagnostics can provide rapid, simple, low-cost, and accurate measurements of specific markers and can also be used in emergency settings. The present systematic review was developed to answer the following question: "Are salivary biomarkers useful in identifying patients with acute myocardial infarction?" METHODS Following the "Preferred Reporting Item for Systematic Reviews and Meta-analysis" (PRISMA) guidelines, we selected 17 papers. The critical appraisal and quality assessment were performed following the National Institute of Health and the classification of the Oxford Center for Evidence-Based Medicine. RESULTS Twenty-six salivary biomarkers were explored in association with AMI. Troponins, C-reactive protein, and adiponectin were the most frequently investigated molecules. We found that the evaluated biomarkers had different levels of diagnostic accuracy in discriminating patients with AMI from healthy controls. We also observed a lack of good-quality studies on the association between the occurrence of AMI and the presence of related salivary biomarkers. CONCLUSIONS There is evidence that salivary isoforms of cardiac troponin, C-reactive protein, and creatine phosphokinase (CPK) could be useful markers for the prompt diagnosis of AMI. However, the effective use of these markers as possible substitutes for serological markers should be confirmed by further studies that avoid the bias highlighted in the present review.
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Affiliation(s)
- Tuttolomondo Domenico
- Department of Cardiology, Parma University Hospital, Via Gramsci 14, 43126 Parma, Italy.
| | - Antonelli Rita
- Centro Universitario di Odontoiatria, University of Parma, Via Gramsci 14, Parma 43126, Italy.
| | - Setti Giacomo
- Centro Universitario di Odontoiatria, University of Parma, Via Gramsci 14, Parma 43126, Italy; Dentistry and Oral and Maxillofacial Surgery-Department of Surgical, Medical, Dental and Morphological Science with interest in Transplant, Oncological and Regenerative Medicine, University of Modena and Reggio Emilia, Largo del Pozzo 71, 41125 Modena, Italy.
| | - Ardissino Diego
- Department of Cardiology, Parma University Hospital, Via Gramsci 14, 43126 Parma, Italy.
| | - Pertinhez Thelma
- Department of Medicine and Surgery, University of Parma, Via Volturno 39, 43126 Parma, Italy.
| | - Gallo Mariana
- Department of Medicine and Surgery, University of Parma, Via Volturno 39, 43126 Parma, Italy.
| | - Niccoli Giampaolo
- Department of Cardiology, Parma University Hospital, Via Gramsci 14, 43126 Parma, Italy.
| | - Nicolini Francesco
- Department of Cardiac Surgery, Parma University Hospital, Via Gramsci 14, 43126 Parma, Italy.
| | - Georgaki Maria
- Department of Oral Medicine & Pathology and Hospital Dentistry, School of Dentistry, National and Kapodistrian University of Athens, 2 Thivon Str., 11527, Goudi, Athens, Greece
| | - Formica Francesco
- Department of Cardiac Surgery, Parma University Hospital, Via Gramsci 14, 43126 Parma, Italy.
| | - Borrello Bruno
- Department of Cardiac Surgery, Parma University Hospital, Via Gramsci 14, 43126 Parma, Italy.
| | - Meleti Marco
- Centro Universitario di Odontoiatria, University of Parma, Via Gramsci 14, Parma 43126, Italy.
| | - Cassi Diana
- Dentistry and Oral and Maxillofacial Surgery-Department of Surgical, Medical, Dental and Morphological Science with interest in Transplant, Oncological and Regenerative Medicine, University of Modena and Reggio Emilia, Largo del Pozzo 71, 41125 Modena, Italy.
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12
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McRae MP, Rajsri KS, Alcorn TM, McDevitt JT. Smart Diagnostics: Combining Artificial Intelligence and In Vitro Diagnostics. SENSORS (BASEL, SWITZERLAND) 2022; 22:6355. [PMID: 36080827 PMCID: PMC9459970 DOI: 10.3390/s22176355] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 08/12/2022] [Accepted: 08/19/2022] [Indexed: 06/15/2023]
Abstract
We are beginning a new era of Smart Diagnostics-integrated biosensors powered by recent innovations in embedded electronics, cloud computing, and artificial intelligence (AI). Universal and AI-based in vitro diagnostics (IVDs) have the potential to exponentially improve healthcare decision making in the coming years. This perspective covers current trends and challenges in translating Smart Diagnostics. We identify essential elements of Smart Diagnostics platforms through the lens of a clinically validated platform for digitizing biology and its ability to learn disease signatures. This platform for biochemical analyses uses a compact instrument to perform multiclass and multiplex measurements using fully integrated microfluidic cartridges compatible with the point of care. Image analysis digitizes biology by transforming fluorescence signals into inputs for learning disease/health signatures. The result is an intuitive Score reported to the patients and/or providers. This AI-linked universal diagnostic system has been validated through a series of large clinical studies and used to identify signatures for early disease detection and disease severity in several applications, including cardiovascular diseases, COVID-19, and oral cancer. The utility of this Smart Diagnostics platform may extend to multiple cell-based oncology tests via cross-reactive biomarkers spanning oral, colorectal, lung, bladder, esophageal, and cervical cancers, and is well-positioned to improve patient care, management, and outcomes through deployment of this resilient and scalable technology. Lastly, we provide a future perspective on the direction and trajectory of Smart Diagnostics and the transformative effects they will have on health care.
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Affiliation(s)
- Michael P. McRae
- Department of Molecular Pathobiology, Division of Biomaterials, Bioengineering Institute, New York University College of Dentistry, 433 First Ave. Rm 822, New York, NY 10010, USA
| | - Kritika S. Rajsri
- Department of Molecular Pathobiology, Division of Biomaterials, Bioengineering Institute, New York University College of Dentistry, 433 First Ave. Rm 822, New York, NY 10010, USA
- Department of Pathology, Vilcek Institute, New York University School of Medicine, 160 E 34th St, New York, NY 10016, USA
| | - Timothy M. Alcorn
- Latham BioPharm Group, 6810 Deerpath Rd Suite 405, Elkridge, MD 21075, USA
| | - John T. McDevitt
- Department of Molecular Pathobiology, Division of Biomaterials, Bioengineering Institute, New York University College of Dentistry, 433 First Ave. Rm 822, New York, NY 10010, USA
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13
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Komarova N, Panova O, Titov A, Kuznetsov A. Aptamers Targeting Cardiac Biomarkers as an Analytical Tool for the Diagnostics of Cardiovascular Diseases: A Review. Biomedicines 2022; 10:biomedicines10051085. [PMID: 35625822 PMCID: PMC9138532 DOI: 10.3390/biomedicines10051085] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 05/05/2022] [Accepted: 05/06/2022] [Indexed: 02/04/2023] Open
Abstract
The detection of cardiac biomarkers is used for diagnostics, prognostics, and the risk assessment of cardiovascular diseases. The analysis of cardiac biomarkers is routinely performed with high-sensitivity immunological assays. Aptamers offer an attractive alternative to antibodies for analytical applications but, to date, are not widely practically implemented in diagnostics and medicinal research. This review summarizes the information on the most common cardiac biomarkers and the current state of aptamer research regarding these biomarkers. Aptamers as an analytical tool are well established for troponin I, troponin T, myoglobin, and C-reactive protein. For the rest of the considered cardiac biomarkers, the isolation of novel aptamers or more detailed characterization of the known aptamers are required. More attention should be addressed to the development of dual-aptamer sandwich detection assays and to the studies of aptamer sensing in alternative biological fluids. The universalization of aptamer-based biomarker detection platforms and the integration of aptamer-based sensing to clinical studies are demanded for the practical implementation of aptamers to routine diagnostics. Nevertheless, the wide usage of aptamers for the diagnostics of cardiovascular diseases is promising for the future, with respect to both point-of-care and laboratory testing.
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14
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Clephane K, O'Loughlin JI, Bodnar TS, Wilson MC, Stariha JT, Craig AN, Weinberg J, Brotto LA, Lorenz TK. Lack of Evidence for a Relationship Between Salivary CRP and Women's Sexual Desire: An Investigation Across Clinical and Healthy Samples. J Sex Med 2022; 19:745-760. [PMID: 35296386 PMCID: PMC9064911 DOI: 10.1016/j.jsxm.2022.02.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 01/29/2022] [Accepted: 02/04/2022] [Indexed: 01/08/2023]
Abstract
BACKGROUND Inflammation has been linked to a variety of mental and physical health outcomes that disproportionately impact women, and which can impair sexual function; thus, there is reason to expect a link between inflammation and women's sexual functioning. AIM To test the hypothesis that higher concentrations of C-reactive protein (CRP), a general biomarker of inflammation, would predict women's lower sexual desire. METHOD As 2 independent research teams, we conducted 3 separate studies (total n = 405) that assessed salivary CRP and various measurements of sexual desire in different women populations. OUTCOMES Female Sexual Function Index, Sexual Desire Inventory-2, Decreased Sexual Desire Screener, and Sexual Interest and Desire Inventory. RESULTS Regardless of the way sexual desire was measured (e.g., state vs trait; general desire vs. desire functioning) and the population sampled (i.e., healthy vs. clinically diagnosed with sexual dysfunction), all the studies revealed null results. CLINICAL IMPLICATIONS While exploratory, the convergence of these null results across studies and researchers suggests that if there is an association between inflammation and women's sexual desire, it is likely very subtle. STRENGTHS & LIMITATIONS Across 2 independent research teams, 3 unrelated studies, and various measurements of sexual desire, results were consistent. These points lend to the generalizability of the results. However, study designs were cross-sectional. CONCLUSIONS Future research may reveal (i) a non-linear threshold effect, such that inflammation does not begin to impact women's sexual desire until it is at a high level, (ii) inflammatory biomarkers other than CRP might be more sensitive in detecting associations between inflammation and desire, should they exist, or (iii) the mechanisms underlying sexual dysfunction may differ between sexes. Clephane K, et al. Lack of Evidence for a Relationship Between Salivary CRP and Women's Sexual Desire: An Investigation Across Clinical and Healthy Samples. J Sex Med 2022;19:745-760.
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Affiliation(s)
- Kirstin Clephane
- University of Nebraska - Lincoln, Center for Brain, Biology and Behavior, Lincoln, NE, USA; University of Nebraska - Lincoln, Psychology Department, Lincoln, NE, USA
| | - Julia I O'Loughlin
- University of British Columbia, Department of Educational and Counselling Psychology, and Special Education, Vancouver, British Columbia, CA, USA
| | - Tamara S Bodnar
- University of British Columbia, Department of Cellular and Physiological Sciences, Vancouver, British Columbia, CA, USA
| | - M Claire Wilson
- Indiana University, Department of Psychological and Brain Sciences, Bloomington, IN, USA
| | - Jordan Tb Stariha
- University of British Columbia, Department of Obstetrics and Gynecology, Vancouver, British Columbia, CA, USA
| | - Amber N Craig
- Medical College of Wisconsin, Department of Psychiatry and Behavioral Medicine, Milwaukee, WI, USA
| | - Joanne Weinberg
- University of British Columbia, Department of Cellular and Physiological Sciences, Vancouver, British Columbia, CA, USA
| | - Lori A Brotto
- University of British Columbia, Department of Obstetrics and Gynecology, Vancouver, British Columbia, CA, USA; University of British Columbia, Faculty of Medicine, Vancouver, British Columbia, CA, USA
| | - Tierney K Lorenz
- University of Nebraska - Lincoln, Center for Brain, Biology and Behavior, Lincoln, NE, USA; University of Nebraska - Lincoln, Psychology Department, Lincoln, NE, USA.
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15
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Chaulin AM. Features of the Metabolisms of Cardiac Troponin Molecules-Part 1: The Main Stages of Metabolism, Release Stage. Curr Issues Mol Biol 2022; 44:1376-1394. [PMID: 35723315 PMCID: PMC8947512 DOI: 10.3390/cimb44030092] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 03/08/2022] [Accepted: 03/09/2022] [Indexed: 11/17/2022] Open
Abstract
Cardiac troponins (cTns) have long been the most valuable and specific biomarkers for detecting ischemic myocardial cells (MCs) injury, which is one of the key signs of myocardial infarction (MI). Modern methods (highly sensitive and ultra-sensitive immunoassays (hs-cTns)) of detection are an important and indispensable tool for the early diagnosis of MI and the choice of patient management protocols. Timely diagnosis of MI can significantly improve the prognosis of patients. However, in real clinical practice, doctors often face a significant problem when using cTns-the difficulty of differential diagnosis due to frequent and unexplained increases in the concentration of cTns in blood serum. In addition, there is conflicting information that may potentially affect the diagnostic capabilities and value of cTns: the influence of certain biological factors (diurnal rhythm, gender and age) on serum cTns levels; extra-cardiac expression of cTns; the possibilities of non-invasive diagnosis of MI; and other pathological conditions that cause non-ischemic injury to MCs. To solve these problems, it is necessary to concentrate on studying the metabolism of cTns. The review of our current knowledge about cTns metabolism consists of two parts. In this (first) part of the manuscript, the main stages of cTns metabolism are briefly described and the mechanisms of cTns release from MCs are considered in detail.
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Affiliation(s)
- Aleksey Michailovich Chaulin
- Department of Cardiology and Cardiovascular Surgery, Medical Faculty, Samara State Medical University, 443099 Samara, Russia
- Department of Clinical Chemistry, Samara Regional Clinical Cardiological Dispensary, 443070 Samara, Russia
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16
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Rammos A, Bechlioulis A, Kalogeras P, Tripoliti EE, Goletsis Y, Kalivi A, Blathra E, Salvo P, Trivella MG, Lomonaco T, Fuoco R, Bellagambi F, Watson CJ, Errachid A, Fotiadis DI, Michalis LK, Naka KK. Salivary Biomarkers for Diagnosis and Therapy Monitoring in Patients with Heart Failure. A Systematic Review. Diagnostics (Basel) 2021; 11:824. [PMID: 34063278 PMCID: PMC8147430 DOI: 10.3390/diagnostics11050824] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 04/26/2021] [Accepted: 04/30/2021] [Indexed: 11/16/2022] Open
Abstract
The aim of this study was to perform a systematic review on the potential value of saliva biomarkers in the diagnosis, management and prognosis of heart failure (HF). The correlation between saliva and plasma values of these biomarkers was also studied. PubMed was searched to collect relevant literature, i.e., case-control, cross-sectional studies that either compared the values of salivary biomarkers among healthy subjects and HF patients, or investigated their role in risk stratification and prognosis in HF patients. No randomized control trials were included. The search ended on 31st of December 2020. A total of 15 studies met the inclusion criteria. 18 salivary biomarkers were analyzed and the levels of all biomarkers studied were found to be higher in HF patients compared to controls, except for amylase, sodium, and chloride that had smaller saliva concentrations in HF patients. Natriuretic peptides are the most commonly used plasma biomarkers in the management of HF. Their saliva levels show promising results, although the correlation of saliva to plasma values is weakened in higher plasma values. In most of the publications, differences in biomarker levels between HF patients and controls were found to be statistically significant. Due to the small number of patients included, larger studies need to be conducted in order to facilitate the use of saliva biomarkers in clinical practice.
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Affiliation(s)
- Aidonis Rammos
- Second Department of Cardiology, Faculty of Medicine, School of Health Sciences, University of Ioannina and University Hospital of Ioannina, GR 45500 Ioannina, Greece; (A.R.); (A.B.); (P.K.); (A.K.); (E.B.); (L.K.M.)
| | - Aris Bechlioulis
- Second Department of Cardiology, Faculty of Medicine, School of Health Sciences, University of Ioannina and University Hospital of Ioannina, GR 45500 Ioannina, Greece; (A.R.); (A.B.); (P.K.); (A.K.); (E.B.); (L.K.M.)
| | - Petros Kalogeras
- Second Department of Cardiology, Faculty of Medicine, School of Health Sciences, University of Ioannina and University Hospital of Ioannina, GR 45500 Ioannina, Greece; (A.R.); (A.B.); (P.K.); (A.K.); (E.B.); (L.K.M.)
| | - Evanthia E. Tripoliti
- Department of Biomedical Research, Institute of Molecular Biology and Biotechnology, FORTH, GR 45110 Ioannina, Greece; (E.E.T.); (Y.G.); (D.I.F.)
| | - Yorgos Goletsis
- Department of Biomedical Research, Institute of Molecular Biology and Biotechnology, FORTH, GR 45110 Ioannina, Greece; (E.E.T.); (Y.G.); (D.I.F.)
- Department of Economics, University of Ioannina, GR 45110 Ioannina, Greece
| | - Anna Kalivi
- Second Department of Cardiology, Faculty of Medicine, School of Health Sciences, University of Ioannina and University Hospital of Ioannina, GR 45500 Ioannina, Greece; (A.R.); (A.B.); (P.K.); (A.K.); (E.B.); (L.K.M.)
| | - Effrosyni Blathra
- Second Department of Cardiology, Faculty of Medicine, School of Health Sciences, University of Ioannina and University Hospital of Ioannina, GR 45500 Ioannina, Greece; (A.R.); (A.B.); (P.K.); (A.K.); (E.B.); (L.K.M.)
| | - Pietro Salvo
- Institute of Clinical Physiology, Italian National Research Council, Via G. Moruzzi 1, PI 56124 Pisa, Italy; (P.S.); (M.G.T.)
| | - M. Giovanna Trivella
- Institute of Clinical Physiology, Italian National Research Council, Via G. Moruzzi 1, PI 56124 Pisa, Italy; (P.S.); (M.G.T.)
| | - Tommaso Lomonaco
- Department of Chemistry and Industrial Chemistry, University of Pisa, PI 56124 Pisa, Italy; (T.L.); (R.F.); (F.B.)
| | - Roger Fuoco
- Department of Chemistry and Industrial Chemistry, University of Pisa, PI 56124 Pisa, Italy; (T.L.); (R.F.); (F.B.)
| | - Francesca Bellagambi
- Department of Chemistry and Industrial Chemistry, University of Pisa, PI 56124 Pisa, Italy; (T.L.); (R.F.); (F.B.)
- Institute of Analytical Sciences (ISA)—UMR 5280, University Claude Bernard Lyon 1, 69100 Lyon, France;
| | - Chris J. Watson
- UCD Conway Institute, School of Medicine, University College Dublin, DUBLIN 4, Dublin, Ireland;
- Wellcome-Wolfson Institute for Experimental Medicine, Queen’s University Belfast, Belfast BT97BL, UK
| | - Abdelhamid Errachid
- Institute of Analytical Sciences (ISA)—UMR 5280, University Claude Bernard Lyon 1, 69100 Lyon, France;
| | - Dimitrios I. Fotiadis
- Department of Biomedical Research, Institute of Molecular Biology and Biotechnology, FORTH, GR 45110 Ioannina, Greece; (E.E.T.); (Y.G.); (D.I.F.)
- Department of Economics, University of Ioannina, GR 45110 Ioannina, Greece
- Unit of Medical Technology and Intelligent Information Systems, University of Ioannina, GR 45110 Ioannina, Greece
| | - Lampros K. Michalis
- Second Department of Cardiology, Faculty of Medicine, School of Health Sciences, University of Ioannina and University Hospital of Ioannina, GR 45500 Ioannina, Greece; (A.R.); (A.B.); (P.K.); (A.K.); (E.B.); (L.K.M.)
| | - Katerina K. Naka
- Second Department of Cardiology, Faculty of Medicine, School of Health Sciences, University of Ioannina and University Hospital of Ioannina, GR 45500 Ioannina, Greece; (A.R.); (A.B.); (P.K.); (A.K.); (E.B.); (L.K.M.)
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17
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Bahbah EI, Noehammer C, Pulverer W, Jung M, Weinhaeusel A. Salivary biomarkers in cardiovascular disease: An insight into the current evidence. FEBS J 2020; 288:6392-6405. [PMID: 33370493 DOI: 10.1111/febs.15689] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Revised: 11/28/2020] [Accepted: 12/23/2020] [Indexed: 01/08/2023]
Abstract
Cardiovascular diseases (CVDs) are the most common cause of mortality worldwide. In acute cardiovascular conditions, time is a crucial player in the outcomes of disease management. Given the ease and noninvasiveness of obtaining saliva, salivary biomarkers may provide a rapid and efficient diagnosis of CVD. Here, we reviewed the published data on the value of salivary molecules for diagnosis of CVD, especially in acute care settings. In this review, we show that some biomarkers such as salivary creatinine kinase myocardial band, C-reactive protein, troponin-1, and myoglobin exhibited promising diagnostic values that were comparable to their serum counterparts. Other molecules were also investigated and showed controversial results, including myeloperoxidase, brain natriuretic peptide, and some oxidative stress markers. Based on our review, we concluded that the clinical use of salivary biomarkers to diagnose CVD is promising; however, it is still in the early stage of development. Further studies are needed to validate these findings, determine cutoff values for diagnosis, and compare them to other established biomarkers currently in clinical use.
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Affiliation(s)
- Eshak I Bahbah
- AIT Molecular Diagnostics, Center for Health & Bioresources, AIT Austrian Institute of Technology GmbH, Vienna, Austria.,Faculty of Medicine, Al-Azhar University, Damietta, Egypt
| | - Christa Noehammer
- AIT Molecular Diagnostics, Center for Health & Bioresources, AIT Austrian Institute of Technology GmbH, Vienna, Austria
| | - Walter Pulverer
- AIT Molecular Diagnostics, Center for Health & Bioresources, AIT Austrian Institute of Technology GmbH, Vienna, Austria
| | - Martin Jung
- AIT Molecular Diagnostics, Center for Health & Bioresources, AIT Austrian Institute of Technology GmbH, Vienna, Austria
| | - Andreas Weinhaeusel
- AIT Molecular Diagnostics, Center for Health & Bioresources, AIT Austrian Institute of Technology GmbH, Vienna, Austria
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18
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Sensitive immunoassay of cardiac troponin I using an optimized microelectrode array in a novel integrated microfluidic electrochemical device. Anal Bioanal Chem 2020; 412:8325-8338. [DOI: 10.1007/s00216-020-02968-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 09/15/2020] [Accepted: 09/22/2020] [Indexed: 02/07/2023]
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19
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Bor G, Man E, Ugurlu O, Ceylan AE, Balaban S, Durmus C, Pinar Gumus Z, Evran S, Timur S. in vitro
Selection of Aptamer for Imidacloprid Recognition as Model Analyte and Construction of a Water Analysis Platform. ELECTROANAL 2020. [DOI: 10.1002/elan.202000075] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Affiliation(s)
- Gulsah Bor
- Department of Biochemistry Faculty of Science Ege University 35100 Izmir Turkey
| | - Ezgi Man
- Department of Biochemistry Faculty of Science Ege University 35100 Izmir Turkey
| | - Ozge Ugurlu
- Department of Biochemistry Faculty of Science Ege University 35100 Izmir Turkey
| | - Ayse Elcin Ceylan
- Department of Biochemistry Faculty of Science Ege University 35100 Izmir Turkey
| | - Simge Balaban
- Department of Biochemistry Faculty of Science Ege University 35100 Izmir Turkey
| | - Ceren Durmus
- Department of Biochemistry Faculty of Science Ege University 35100 Izmir Turkey
| | - Z. Pinar Gumus
- Central Research Test and Analysis Laboratory Application and Research Center Ege University 35100 Izmir Turkey
| | - Serap Evran
- Department of Biochemistry Faculty of Science Ege University 35100 Izmir Turkey
| | - Suna Timur
- Department of Biochemistry Faculty of Science Ege University 35100 Izmir Turkey
- Central Research Test and Analysis Laboratory Application and Research Center Ege University 35100 Izmir Turkey
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20
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Hashavya S, Pines N, Gayego A, Schechter A, Gross I, Moses A. The use of bacterial DNA from saliva for the detection of GAS pharyngitis. J Oral Microbiol 2020; 12:1771065. [PMID: 33312447 PMCID: PMC7717604 DOI: 10.1080/20002297.2020.1771065] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
Background Acute tonsillitis is a very common medical condition. Despite different methods of detection, all tests are based on GAS sampling using a throat swab. However, obtaining the swab can elicit vomiting and is often accompanied by fear and apprehension in children. The aim of this study was to find a non-invasive method for the detection of GAS pharyngitis. Methods A classic throat swab was obtained for culture, and a saliva sample was taken from 100 subjects recruited from Meuhedet Health Care Organization clinic. Real time PCR was performed to detect GAS dnaseB specific gene in the saliva samples. Results 56% of the throat cultures and 48% of the PCR samples were positive for GAS. The overall sensitivity and specificity of the saliva PCR method was 79% and 91% respectively; NPV and PPV were 77% and 92% respectively. When excluding patients who presented on the first day of fever, sensitivity and specificity increased to 90% and 100% respectively. No other anamnestic or clinical findings increased the yield of the test. Conclusion Saliva-based PCR amplification of GAS DNA method is effective in detection of GAS pharyngitis. Further studies are needed to achieve detection rates to replace the traditional throat swab-based approach.
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Affiliation(s)
- Saar Hashavya
- Department of Pediatric Emergency Medicine, Hadassah Medical Center, Jerusalem, Israel
| | - Naama Pines
- Department of Pediatrics, Hadassah and Hebrew University Hospital, Jerusalem, Israel
| | - Ayelet Gayego
- Department of Microbiology and Infectious Diseases, Hadassah and Hebrew University Hospital, Jerusalem, Israel
| | | | - Itai Gross
- Department of Pediatric Emergency Medicine, Hadassah Medical Center, Jerusalem, Israel
| | - Alon Moses
- Department of Microbiology and Infectious Diseases, Hadassah and Hebrew University Hospital, Jerusalem, Israel
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Meleti M, Cassi D, Vescovi P, Setti G, Pertinhez TA, Pezzi ME. Salivary biomarkers for diagnosis of systemic diseases and malignant tumors. A systematic review. Med Oral Patol Oral Cir Bucal 2020; 25:e299-e310. [PMID: 32040469 PMCID: PMC7103445 DOI: 10.4317/medoral.23355] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2019] [Accepted: 08/06/2019] [Indexed: 12/18/2022] Open
Abstract
Background Saliva evaluation could be a possible alternative to blood and/or tissue analyses, for researching specific molecules associated to the presence of systemic diseases and malignancies.
The present systematic review has been designed in order to answer to the question “are there significant associations between specific salivary biomarkers and diagnosis of systemic diseases or malignancies?”.
Material and Methods The Preferred Reporting Item for Systematic Reviews and Meta-analysis (PRISMA) statement was used to guide the review.
The combinations of “saliva” and “systemic diseases” or “diagnosis” or “biomarkers” or “cancers” or “carcinoma” or “tumors”, were used to search Medline, Scopus and Web of Science databases. Endpoint of research has been set at May 2019.
Studies were classified into 3 groups according to the type of disease investigated for diagnosis: 1) malignant tumors; 2) neurologic diseases and 3) inflammatory/metabolic/cardiovascular diseases.
Assessment of quality has been assigned according to a series of questions proposed by the National Institute of Health. Level of evidence was assessed using the categories proposed in the Oxford Center for Evidence-Based medicine (CEMB) levels for diagnosis (2011).
Results Seventy-nine studies met the inclusion and exclusion criteria. Fifty-one (64%) investigated malignant tumors, 14 (17.5%) neurologic and 14 (18.5%) inflammatory/cardiovascular/metabolic diseases.
Among studies investigating malignant tumors, 12 (23.5%) were scored as “good” and 11 of these reported statistically significant associations between salivary molecules and pathology. Two and 5 studies were found to have a good quality, among those evaluating the association between salivary biomarkers and neurologic and inflammatory/metabolic/cardiovascular diseases, respectively.
Conclusions The present systematic review confirms the existence of some “good” quality evidence to support the role of peculiar salivary biomarkers for diagnosis of systemic diseases (e.g. lung cancer and EGFR). Key words:Salivary diagnostics, biomarkers, systemic diseases, malignant tumors, early diagnosis.
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Affiliation(s)
- M Meleti
- Centro Universitario di Odontoiatria Via Gramsci 14. 43126, Parma, Italy
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22
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Setti G, Pezzi ME, Viani MV, Pertinhez TA, Cassi D, Magnoni C, Bellini P, Musolino A, Vescovi P, Meleti M. Salivary MicroRNA for Diagnosis of Cancer and Systemic Diseases: A Systematic Review. Int J Mol Sci 2020; 21:E907. [PMID: 32019170 PMCID: PMC7037322 DOI: 10.3390/ijms21030907] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Revised: 01/24/2020] [Accepted: 01/29/2020] [Indexed: 12/13/2022] Open
Abstract
: Background: The aberrant expression of microRNAs (miRNAs) has been associated with several diseases, including cancer, inflammatory, and autoimmune conditions. Interest in salivary miRNAs as non-invasive tools for the diagnosis of malignancies and systemic diseases is rapidly increasing. The present systematic review was developed for answering the question: "Are salivary microRNAs reliable biomarkers for diagnosis of cancer and systemic diseases?" METHODS The application of inclusion and exclusion criteria led to the selection of 11 papers. Critical appraisals and quality assessments of the selected studies were performed through the National Institute of Health "Study Quality Assessment Tool" and the classification of the Oxford Center for Evidence-Based Medicine. RESULTS Seven studies reported statistically significant correlations between one or more salivary miRNAs and the investigated disease. The critical analysis allowed us to classify only two studies (18.2%) as having "good" quality, the rest being scored as "intermediate" (8; 73%) and "poor" (1; 9%). Evidence exists that salivary miR-940 and miR-3679-5p are reliable markers for pancreatic cancer and that miR140-5p and miR301a are promising molecules for the salivary diagnosis of gastric cancer. CONCLUSIONS Further studies, possibly avoiding the risk of bias highlighted here, are necessary to consolidate these findings and to identify new reliable salivary biomarkers.
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Affiliation(s)
- Giacomo Setti
- Molecular Medicine Ph.D. School, Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy
- Dentistry and Oral and Maxillofacial Surgery—Department of Surgical, Medical, Dental and Morphological Science with interest in Transplant Oncological and Regenerative Medicine—University of Modena and Reggio Emilia, Largo del Pozzo 71, 41125 Modena, Italy;
| | - Margherita E. Pezzi
- Centro Universitario di Odontoiatria—University of Parma, Via Gramsci 14, 43126 Parma, Italy; (M.E.P.); (M.V.V.); (D.C.); (P.V.); (M.M.)
| | - Maria Vittoria Viani
- Centro Universitario di Odontoiatria—University of Parma, Via Gramsci 14, 43126 Parma, Italy; (M.E.P.); (M.V.V.); (D.C.); (P.V.); (M.M.)
| | - Thelma A. Pertinhez
- Department of Medicine and Surgery—Via Volturno 39, 43125 Parma, Italy;
- Transfusion Medicine Unit, Azienda USL—IRCCS di Reggio Emilia—Viale Umberto I, 50, 42123 Reggio Emilia, Italy
| | - Diana Cassi
- Centro Universitario di Odontoiatria—University of Parma, Via Gramsci 14, 43126 Parma, Italy; (M.E.P.); (M.V.V.); (D.C.); (P.V.); (M.M.)
| | - Cristina Magnoni
- Dermatology—Department of Surgical, Medical, Dental and Morphological Science with interest in Transplant Oncological and Regenerative Medicine—University of Modena and Reggio Emilia, Largo del Pozzo 71, 41125 Modena, Italy;
| | - Pierantonio Bellini
- Dentistry and Oral and Maxillofacial Surgery—Department of Surgical, Medical, Dental and Morphological Science with interest in Transplant Oncological and Regenerative Medicine—University of Modena and Reggio Emilia, Largo del Pozzo 71, 41125 Modena, Italy;
| | - Antonino Musolino
- Medical Oncology and Breast Unit, University Hospital of Parma – Via Gramsci 14, 43125 Parma, Italy;
| | - Paolo Vescovi
- Centro Universitario di Odontoiatria—University of Parma, Via Gramsci 14, 43126 Parma, Italy; (M.E.P.); (M.V.V.); (D.C.); (P.V.); (M.M.)
| | - Marco Meleti
- Centro Universitario di Odontoiatria—University of Parma, Via Gramsci 14, 43126 Parma, Italy; (M.E.P.); (M.V.V.); (D.C.); (P.V.); (M.M.)
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Chaulin AM, Karslyan LS, Bazyuk EV, Nurbaltaeva DA, Duplyakov DV. [Clinical and Diagnostic Value of Cardiac Markers in Human Biological Fluids]. ACTA ACUST UNITED AC 2019; 59:66-75. [PMID: 31849301 DOI: 10.18087/cardio.2019.11.n414] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Accepted: 03/22/2019] [Indexed: 11/18/2022]
Abstract
The article is devoted to problems of clinical-diagnostic value of determination of cardio-specific troponins in human biological fluids. Improvement of laboratory instrumentation and emergence of high sensitivity methods of analysis have allowed to identify troponins in urine, dialysate, and oral fluid. In the review we present actual information related to measurement of troponins in blood serum, data on testing of cardio-specific troponins in urine, dialysate, and oral fluid. Special attention is paid to determination of some cardiomarkers in oral fluid with thorough analysis of diagnostic value and effectiveness of the conducted studies.
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Affiliation(s)
- A M Chaulin
- Samara State Medical University; Samara Regional Cardiology Dispensary
| | - L S Karslyan
- Samara State Medical University; Samara Regional Cardiology Dispensary
| | | | | | - D V Duplyakov
- Samara State Medical University; Samara Regional Cardiology Dispensary
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24
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Pay JB, Shaw AM. Towards salivary C-reactive protein as a viable biomarker of systemic inflammation. Clin Biochem 2019; 68:1-8. [DOI: 10.1016/j.clinbiochem.2019.04.006] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Revised: 03/08/2019] [Accepted: 04/08/2019] [Indexed: 12/13/2022]
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Tripoliti EE, Ioannidou P, Toumpaniaris P, Rammos A, Pacitto D, Lourme JC, Goletsis Y, Naka KK, Errachid A, Fotiadis DI. Point-of-Care Testing Devices for Heart Failure Analyzing Blood and Saliva Samples. IEEE Rev Biomed Eng 2019; 13:17-31. [PMID: 30892234 DOI: 10.1109/rbme.2019.2905730] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Heart failure (HF) is the most rapidly growing cardiovascular condition with an estimated prevalence of >37.7 million individuals globally. HF is associated with increased mortality and morbidity and confers a substantial burden, in terms of cost and quality of life, for the individuals and the healthcare systems, highlighting thus the need for early and accurate diagnosis of HF. The accuracy of HF diagnosis, severity estimation, and prediction of adverse events has improved by the utilization of blood tests measuring biomarkers. The contribution of biomarkers for HF management is intensified by the fact that they can be measured in short time at the point-of-care. This is allowed by the development of portable analytical devices, commonly known as point-of-care testing (POCT) devices, which exploit the advancements in the area of microfluidics and nanotechnology. The aim of this review paper is to present a review of POCT devices used for the measurement of biomarkers facilitating decision making when managing HF patients. The devices are either commercially available or in the form of prototypes under development. Both blood and saliva samples are considered. The challenges concerning the implementation of POCT devices and the barriers for their adoption in clinical practice are discussed.
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Prims S, Van Raemdonck G, Vanden Hole C, Van Cruchten S, Van Ginneken C, Van Ostade X, Casteleyn C. On the characterisation of the porcine gland-specific salivary proteome. J Proteomics 2019; 196:92-105. [DOI: 10.1016/j.jprot.2019.01.016] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2017] [Revised: 01/14/2019] [Accepted: 01/25/2019] [Indexed: 12/22/2022]
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Salivary Exosomes as Nanocarriers for Cancer Biomarker Delivery. MATERIALS 2019; 12:ma12040654. [PMID: 30795593 PMCID: PMC6416587 DOI: 10.3390/ma12040654] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Revised: 02/16/2019] [Accepted: 02/18/2019] [Indexed: 01/01/2023]
Abstract
Human saliva is an ideal body fluid for developing non-invasive diagnostics. Saliva contains naturally-occurring nanoparticles with unique structural and biochemical characteristics. The salivary exosome, a nanoscale extracellular vesicle, has been identified as a highly informative nanovesicle with clinically-relevant information. Salivary exosomes have brought forth a pathway and mechanism by which cancer-derived biomarkers can be shuttled through the systemic circulation into the oral cavity. Despite such clinical potential, routine and reliable analyses of exosomes remain challenging due to their small sizes. Characterization of individual exosome nanostructures provides critical data for understanding their pathophysiological condition and diagnostic potential. In this review, we summarize a current array of discovered salivary biomarkers and nanostructural properties of salivary exosomes associated with specific cancers. In addition, we describe a novel electrochemical sensing technology, EFIRM (electric field-induced release and measurement), that advances saliva liquid biopsy, covering the current landscape of point-of-care saliva testing.
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A New Approach for the Diagnosis of Systemic and Oral Diseases Based on Salivary Biomolecules. DISEASE MARKERS 2019; 2019:8761860. [PMID: 30906485 PMCID: PMC6398069 DOI: 10.1155/2019/8761860] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/10/2018] [Revised: 12/18/2018] [Accepted: 01/29/2019] [Indexed: 12/20/2022]
Abstract
Early diagnosis represents the target of contemporary medicine and has an important role in the prognosis and further treatment. Saliva is a biofluid that generated a high interest among researchers due to its multiple advantages over other body fluids. The multitude of components that can act as biomarkers influenced the existing technologies to develop protocols that could allow saliva to become the new noninvasive diagnostic method. Saliva as a diagnostic tool can bring substantial addition to the diagnostic armamentarium, providing important information about oral and general health. The diagnostic applications of saliva extended and had a rapid evolution due to the advancement in salivaomics. The present review summarizes the latest researches in saliva-related studies and explores the information and correlations that saliva can offer regarding the systemic and oral diseases, highlighting its great potential of diagnosis. It is expected that in the future specific guidelines and results regarding the salivary diagnostics are to be available, together with high-sensitivity and specificity tests for multiple systemic and oral diseases.
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Mahmood Z, Enocsson H, Bäck M, Chung RWS, Lundberg AK, Jonasson L. Salivary and plasma levels of matrix metalloproteinase-9 and myeloperoxidase at rest and after acute physical exercise in patients with coronary artery disease. PLoS One 2019; 14:e0207166. [PMID: 30726210 PMCID: PMC6364871 DOI: 10.1371/journal.pone.0207166] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2018] [Accepted: 01/09/2019] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Low-grade systemic inflammation is a predictor of recurrent cardiac events in patients with coronary artery disease (CAD). Plasma proteins such as matrix metalloproteinase (MMP)-9 and myeloperoxidase (MPO) have been shown to reflect basal as well as stress-induced inflammation in CAD. Measurements of MMP-9 and MPO in saliva might pose several advantages. Therefore, we investigated whether salivary levels of MMP-9 and MPO corresponded to plasma levels in patients with coronary artery disease (CAD), both at rest and after acute physical exercise. METHODS A bicycle ergometer test was used as a model for stress-induced inflammation. Twenty-three CAD patients performed the test on two occasions 3-6 months apart. Whole unstimulated saliva was collected before, directly after and 30 min after exercise while plasma was collected before and after 30 min. MMP-9 and MPO in saliva and plasma were determined by Luminex. RESULTS MMP-9 and MPO levels were 2- to 4-fold higher in saliva than in plasma. Amongst the saliva samples, and also to a great extent amongst the plasma samples, the levels of both types of protein showed strong intercorrelations between the levels at rest and after exercise during the two visits. However, there were no (or weak) correlations between salivary and plasma MMP-9 and none between salivary and plasma MPO. CONCLUSION We conclude that salivary diagnostics cannot be used to assess systemic levels of MMP-9 and MPO in CAD patients, neither at rest nor after acute physical exercise.
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Affiliation(s)
- Zeid Mahmood
- Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Faculty of Medicine and Health Sciences, Linköping University,Linköping, Sweden
| | - Helena Enocsson
- Division of Neuro and Inflammation Sciences, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
| | - Maria Bäck
- Department of Medical and Health Sciences, Division of Physiotherapy, Faculty of Health Sciences, Linköping University, Linköping, Sweden
- Department of Occupational Therapy and Physiotherapy, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Rosanna W. S. Chung
- Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Faculty of Medicine and Health Sciences, Linköping University,Linköping, Sweden
| | - Anna K. Lundberg
- Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Faculty of Medicine and Health Sciences, Linköping University,Linköping, Sweden
| | - Lena Jonasson
- Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Faculty of Medicine and Health Sciences, Linköping University,Linköping, Sweden
- * E-mail:
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Abstract
Saliva and oral/buccal samples have become increasingly valuable sources of genetic material for clinical applications. The DNA obtained by these samples is of comparable quality to that from blood samples. This, coupled with the ease of collecting saliva and oral/buccal samples, has led to increased numbers of such samples being incorporated into biobanks. This chapter will detail the steps involved in procuring, transporting, and storing saliva, buccal swabs, and oral wash samples for further use in downstream applications.
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Lahdentausta LSJ, Paju S, Mäntylä P, Buhlin K, Tervahartiala T, Pietiäinen M, Alfthan H, Nieminen MS, Sinisalo J, Sorsa T, Pussinen PJ. Saliva and serum biomarkers in periodontitis and coronary artery disease. J Clin Periodontol 2018; 45:1045-1055. [DOI: 10.1111/jcpe.12976] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Revised: 05/14/2018] [Accepted: 07/02/2018] [Indexed: 12/31/2022]
Affiliation(s)
- Laura S. J. Lahdentausta
- Department of Oral and Maxillofacial Diseases; Helsinki University Hospital; University of Helsinki; Helsinki Finland
| | - Susanna Paju
- Department of Oral and Maxillofacial Diseases; Helsinki University Hospital; University of Helsinki; Helsinki Finland
| | - Päivi Mäntylä
- Department of Oral and Maxillofacial Diseases; Helsinki University Hospital; University of Helsinki; Helsinki Finland
- Institute of Dentistry; University of Eastern Finland; Kuopio Finland
- Department of Oral and Maxillofacial Diseases; Kuopio University Hospital; Kuopio Finland
| | - Kåre Buhlin
- Department of Oral and Maxillofacial Diseases; Helsinki University Hospital; University of Helsinki; Helsinki Finland
- Division of Periodontology; Department of Dental Medicine; Karolinska Institutet; Huddinge Sweden
| | - Taina Tervahartiala
- Department of Oral and Maxillofacial Diseases; Helsinki University Hospital; University of Helsinki; Helsinki Finland
| | - Milla Pietiäinen
- Department of Oral and Maxillofacial Diseases; Helsinki University Hospital; University of Helsinki; Helsinki Finland
| | - Henrik Alfthan
- Laboratory, HUSLAB; Helsinki University Hospital; Helsinki Finland
| | - Markku S. Nieminen
- HUCH Heart and Lung Center; Helsinki University Central Hospital; Helsinki Finland
| | - Juha Sinisalo
- HUCH Heart and Lung Center; Helsinki University Central Hospital; Helsinki Finland
| | - Timo Sorsa
- Department of Oral and Maxillofacial Diseases; Helsinki University Hospital; University of Helsinki; Helsinki Finland
- Division of Periodontology; Department of Dental Medicine; Karolinska Institutet; Huddinge Sweden
| | - Pirkko J. Pussinen
- Department of Oral and Maxillofacial Diseases; Helsinki University Hospital; University of Helsinki; Helsinki Finland
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Gohel V, Jones JA, Wehler CJ. Salivary biomarkers and cardiovascular disease: a systematic review. ACTA ACUST UNITED AC 2018; 56:1432-1442. [DOI: 10.1515/cclm-2017-1018] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2017] [Accepted: 02/13/2018] [Indexed: 12/21/2022]
Abstract
Abstract
Background:
The purpose of this systematic review is to summarize the literature examining associations between salivary biomarkers and cardiovascular disease (CVD) status.
Contents:
An advanced search was conducted using MeSH terms related to salivary biomarkers and CVD, and entered into the PubMed, Web of Science, and Google Scholar search databases. Four hundred and thirty-three records were narrowed to 22 accepted articles. Included titles were assessed for quality using the Newcastle-Ottawa scale, and ranked into categories of low, moderate, or high.
Summary:
A total of 40 salivary biomarkers were analyzed among accepted articles. The most studied markers were salivary creatine kinase isoform MB, C-reactive protein (CRP), matrix metalloproteinase-9, troponin I, myeloperoxidase, myoglobin, and brain natriuretic peptide. Salivary CRP provided the most consistent trends. Statistically significant increases of salivary CRP were present with CVD in every study that analyzed it. The remaining six markers demonstrated varying patterns.
Outlook:
Existing studies provide insufficient data to draw definitive conclusions. Current research shows that there is an association between some salivary biomarkers and CVD, but the details of existing studies are conflicting. Despite inconclusive results, the diagnostic potential of saliva shows promise as a non-invasive means of cardiovascular risk assessment.
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Affiliation(s)
- Vishal Gohel
- Boston University Henry M. Goldman School of Dental Medicine , 100 East Newton Street , Boston, MA 02118-2308 , USA
| | - Judith A. Jones
- Boston University Henry M. Goldman School of Dental Medicine , Boston, MA , USA
- University of Detroit Mercy School of Dentistry , Detroit, MI , USA
| | - Carolyn J. Wehler
- Boston University Henry M. Goldman School of Dental Medicine , Boston, MA , USA
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Zhang X, Walsh T, Atherton JJ, Kostner K, Schulz B, Punyadeera C. Identification and Validation of a Salivary Protein Panel to Detect Heart Failure Early. Am J Cancer Res 2017; 7:4350-4358. [PMID: 29158831 PMCID: PMC5695135 DOI: 10.7150/thno.21727] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Accepted: 08/24/2017] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Over 26 million people suffer from heart failure (HF) globally. Current diagnosis of HF relies on clinical evaluation, blood assays and imaging techniques. Our aim is to develop a diagnostic assay to detect HF in at risk individuals within the community using human saliva as a medium, potentially leading to a simple, safe early warning system. METHODS Saliva samples were collected from healthy controls (n=36) and HF patients (n=75). Salivary proteome profiles were analysed by Sequential Window Acquisition of All Theoretical fragment ion spectra - Mass Spectrometry (SWATH-MS). A total of 738 proteins were quantified and 177 proteins demonstrated significant differences between HF patients and healthy controls. Candidate biomarkers were chosen based on their abundance and difference between the two cohorts. A multi-protein panel was developed using logistic regression analysis. The diagnostic performance of the multi-protein panel was assessed using receiver operative characteristic curves. The candidate proteins were further confirmed, using western blot analysis, and validated technically, using an independent biological cohort. RESULTS A group of six proteins were chosen in the discovery phase as potential candidates based on their differences in the abundance between the two cohorts. During the validation phase, two of the proteins were not detected with western blotting and as such were removed. The final panel consists of four proteins with sensitivity of 83.3%, specificity of 62.5% with an area under ROC curve of 0.78 in discriminating healthy controls from NYHA class I/II HF patients, and was validated in a second independent cohort study. CONCLUSION Analysis of salivary proteome using SWATH-MS revealed novel HF-specific protein candidates yielding high diagnostic performance. A multi-centre longitudinal clinical trial will be the next step before clinical implementation of this panel.
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Abdul Rehman S, Khurshid Z, Hussain Niazi F, Naseem M, Al Waddani H, Sahibzada HA, Sannam Khan R. Role of Salivary Biomarkers in Detection of Cardiovascular Diseases (CVD). Proteomes 2017; 5:proteomes5030021. [PMID: 28783097 PMCID: PMC5620538 DOI: 10.3390/proteomes5030021] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2017] [Revised: 08/03/2017] [Accepted: 08/05/2017] [Indexed: 02/07/2023] Open
Abstract
Human whole mouth saliva (WMS) is secreted by salivary glands, namely parotid, submandibular/sublingual and other minor glands of the oral cavity. It is secreted in a systematic way, and contain informative proteins and peptides for the early detection of contagious diseases and organ-related diseases. The role of WMS as a liquid biopsy for the detection of cardiovascular diseases (CVD) through Myoglobin (MYO), Cardiac troponin I (cTnI), Creatine phosphokinase MB (CK-MB), Myeloperoxidase (MPO), brain natriuretic peptide (NT-proBNP), Exosomal miRNA, C-Reactive Protein (CRP), Matrix metalloproteinase-8 (MMP-8), MMP-9 and tissue inhibitor of MMP-8 (TIMP-1), leukotriene B4 has been well reported in last decade, that have been reviewed in the literature comprehensively below.
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Affiliation(s)
- Saad Abdul Rehman
- Department of Orthodontics, College of Dentistry, Karachi Medical and Dental College, Karachi 74700, Pakistan.
| | - Zohaib Khurshid
- Department of Prosthodontics and Implantology, College of Dentistry, King Faisal University, Al-Ahsa 31982, Saudi Arabia.
| | - Fayez Hussain Niazi
- Department of Restorative Dentistry, Dar Al Uloom University, Riyadh 13314, Saudia Arabia.
| | - Mustafa Naseem
- Department of Preventive Dental Sciences, Dar Al Uloom University, Riyadh 13314, Saudia Arabia.
| | - Hamed Al Waddani
- Department of Prosthodontics and Implantology, College of Dentistry, King Faisal University, Al-Ahsa 31982, Saudi Arabia.
| | | | - Rabia Sannam Khan
- Department of Oral Pathology, College of Dentistry, Baqai University, Karachi 74600, Pakistan.
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Khan RS, Khurshid Z, Yahya Ibrahim Asiri F. Advancing Point-of-Care (PoC) Testing Using Human Saliva as Liquid Biopsy. Diagnostics (Basel) 2017; 7:E39. [PMID: 28677648 PMCID: PMC5617939 DOI: 10.3390/diagnostics7030039] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Revised: 06/24/2017] [Accepted: 06/30/2017] [Indexed: 12/22/2022] Open
Abstract
Salivary diagnostics is an emerging field for the encroachment of point of care technology (PoCT). The necessity of the development of point-of-care (PoC) technology, the potential of saliva, identification and validation of biomarkers through salivary diagnostic toolboxes, and a broad overview of emerging technologies is discussed in this review. Furthermore, novel advanced techniques incorporated in devices for the early detection and diagnosis of several oral and systemic diseases in a non-invasive, easily-monitored, less time consuming, and in a personalised way is explicated. The latest technology detection systems and clinical utilities of saliva as a liquid biopsy, electric field-induced release and measurement (EFIRM), biosensors, smartphone technology, microfluidics, paper-based technology, and how their futuristic perspectives can improve salivary diagnostics and reduce hospital stays by replacing it with chairside screening is also highlighted.
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Affiliation(s)
- Rabia Sannam Khan
- Department of Oral Pathology, College of Dentistry, Baqai University, Super Highway, P.O.Box: 2407, Karachi 74600, Pakistan.
| | - Zohaib Khurshid
- Prosthodontics and Implantology, College of Dentistry, King Faisal University, Al-Ahsa 31982, Saudi Arabia.
| | - Faris Yahya Ibrahim Asiri
- Department of Preventive Dentistry, College of Dentistry, King Faisal University, Al-Ahsa 31982, Saudi Arabia.
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Rathnayake N, Buhlin K, Kjellström B, Klinge B, Löwbeer C, Norhammar A, Rydén L, Sorsa T, Tervahartiala T, Gustafsson A. Saliva and plasma levels of cardiac-related biomarkers in post-myocardial infarction patients. J Clin Periodontol 2017; 44:692-699. [PMID: 28453865 DOI: 10.1111/jcpe.12740] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/22/2017] [Indexed: 11/27/2022]
Abstract
AIM To relate cardiac biomarkers, such as cystatin C and growth differentiation factor-15 (GDF-15) in saliva to myocardial infarction (MI) and to periodontal status, and to investigate the relation between salivary and plasma cardiac biomarkers. MATERIALS AND METHODS Two hundred patients with MI admitted to coronary care units and 200 matched controls without MI were included. Dental examination and collection of blood and saliva samples was performed 6-10 weeks after the MI for patients and in close proximity thereafter for controls. Analysing methods: ARCHITECT i4000SR, Immulite 2000 XPi or ELISA. RESULTS The mean age was 62 ± 8 years and 84% were male. Total probing pocket depth, fibrinogen, white blood cell counts and HbA1c were higher in patients than controls. GDF-15 levels correlated with most of the included clinical variables in both study groups. No correlation was found between plasma and saliva levels of cystatin C or GDF-15. CONCLUSION Salivary cystatin C and GDF-15 could not differentiate between MI patients and controls.
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Affiliation(s)
- Nilminie Rathnayake
- Division of Periodontology, Department of Dental Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Solna, Sweden
| | - Kåre Buhlin
- Division of Periodontology, Department of Dental Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Solna, Sweden
| | - Barbro Kjellström
- Cardiology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Solna, Sweden
| | - Bjorn Klinge
- Division of Periodontology, Department of Dental Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Solna, Sweden.,Department of Periodontology, Faculty of Odontology, Malmö University, Malmö, Sweden
| | - Christian Löwbeer
- Department of Clinical Chemistry, Aleris Medilab, Täby, Sweden.,Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden
| | - Anna Norhammar
- Cardiology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Solna, Sweden.,Cardiology Unit, Capio S:t Görans Hospital, Stockholm, Sweden
| | - Lars Rydén
- Cardiology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Solna, Sweden
| | - Timo Sorsa
- Division of Periodontology, Department of Dental Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Solna, Sweden.,Helsinki University Central Hospital, Department of Oral and Maxillofacial Diseases, University of Helsinki, Helsinki, Finland
| | - Taina Tervahartiala
- Helsinki University Central Hospital, Department of Oral and Maxillofacial Diseases, University of Helsinki, Helsinki, Finland
| | - Anders Gustafsson
- Division of Periodontology, Department of Dental Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Solna, Sweden
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Christodoulides NJ, McRae MP, Abram TJ, Simmons GW, McDevitt JT. Innovative Programmable Bio-Nano-Chip Digitizes Biology Using Sensors That Learn Bridging Biomarker Discovery and Clinical Implementation. Front Public Health 2017; 5:110. [PMID: 28589118 PMCID: PMC5441161 DOI: 10.3389/fpubh.2017.00110] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2016] [Accepted: 05/02/2017] [Indexed: 11/13/2022] Open
Abstract
The lack of standard tools and methodologies and the absence of a streamlined multimarker approval process have hindered the translation rate of new biomarkers into clinical practice for a variety of diseases afflicting humankind. Advanced novel technologies with superior analytical performance and reduced reagent costs, like the programmable bio-nano-chip system featured in this article, have potential to change the delivery of healthcare. This universal platform system has the capacity to digitize biology, resulting in a sensor modality with a capacity to learn. With well-planned device design, development, and distribution plans, there is an opportunity to translate benchtop discoveries in the genomics, proteomics, metabolomics, and glycomics fields by transforming the information content of key biomarkers into actionable signatures that can empower physicians and patients for a better management of healthcare. While the process is complicated and will take some time, showcased here are three application areas for this flexible platform that combines biomarker content with minimally invasive or non-invasive sampling, such as brush biopsy for oral cancer risk assessment; serum, plasma, and small volumes of blood for the assessment of cardiac risk and wellness; and oral fluid sampling for drugs of abuse testing at the point of need.
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Affiliation(s)
- Nicolaos J. Christodoulides
- Department of Biomaterials, Bioengineering Institute, New York University College of Dentistry, New York, NY, USA
| | - Michael P. McRae
- Department of Biomaterials, Bioengineering Institute, New York University College of Dentistry, New York, NY, USA
| | | | - Glennon W. Simmons
- Department of Biomaterials, Bioengineering Institute, New York University College of Dentistry, New York, NY, USA
| | - John T. McDevitt
- Department of Biomaterials, Bioengineering Institute, New York University College of Dentistry, New York, NY, USA
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Aro K, Wei F, Wong DT, Tu M. Saliva Liquid Biopsy for Point-of-Care Applications. Front Public Health 2017; 5:77. [PMID: 28443278 PMCID: PMC5387045 DOI: 10.3389/fpubh.2017.00077] [Citation(s) in RCA: 79] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2016] [Accepted: 03/28/2017] [Indexed: 01/05/2023] Open
Abstract
Saliva is a non-invasive biofluid, which is easy to collect, transport, and store. Because of its accessibility and connection to systemic diseases, saliva is one of the best candidates for the advancement of point-of-care medicine, where individuals are able to easily monitor their health status by using portable convenient tools such as smartphones. There are a variety of scenarios with which saliva can be used: studies have been conducted on using saliva to measure stress hormones, enzyme levels, developmental disease biomarkers, and even cancer mutations. If validated biomarkers were combined with high-quality detection tools, saliva would open up a new frontier in high-quality healthcare, allowing physicians and patients to work together for real-time health monitoring and high-impact personalized preventative medicine. One of the most exciting emerging frontiers of saliva is liquid biopsy, which is a non-invasive means to assess the presence and characteristics of cancer in a patient. This article will review current basic knowledge of biomarkers, review their relation to different diseases and conditions, and explore liquid biopsy for point-of-care applications.
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Affiliation(s)
- Katri Aro
- School of Dentistry, University of California Los Angeles, Los Angeles, CA, USA
| | - Fang Wei
- School of Dentistry, University of California Los Angeles, Los Angeles, CA, USA
| | - David T Wong
- School of Dentistry, University of California Los Angeles, Los Angeles, CA, USA
| | - Michael Tu
- School of Dentistry, University of California Los Angeles, Los Angeles, CA, USA
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Salivary Diagnostics-Point-of-Care diagnostics of MMP-8 in dentistry and medicine. Diagnostics (Basel) 2017; 7:diagnostics7010007. [PMID: 28117682 PMCID: PMC5373016 DOI: 10.3390/diagnostics7010007] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2016] [Revised: 01/06/2017] [Accepted: 01/12/2017] [Indexed: 12/12/2022] Open
Abstract
Human saliva is an easily accessible biological fluid and contains a variety of disease-related biomarkers, which makes it a potential diagnostic medium. The clinical use of salivary/oral fluid biomarkers to identify oral and systemic conditions requires the development of non-invasive screening and diagnostic technologies, and is among the main goals of oral fluid researchers. The analysis of the disease-specific oral and systemic biomarkers in saliva and oral fluids (i.e., mouth-rinse, gingival crevicular fluid (GCF) and peri-implantitis sulcular fluid (PISF)) is demanding. Several factors influence their expression and release; these factors include the intracellular location, the molecular size and the flow characteristics of the biological fluid. The type of saliva/oral fluid utilized for the diagnostics affects the analysis. High sensitivity together with sophisticated methods and techniques are essential to get a useful outcome. We describe here a recently developed mouth-rinse that is practical, convenient and inexpensive, as well as PISF chair-side/point of care (PoC) lateral-flow active matrix metalloproteinase (aMMP-8) immunoassays to detect, predict and monitor the course and treatment of periodontitis and peri-implantitis.
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Kaczor-Urbanowicz KE, Martin Carreras-Presas C, Aro K, Tu M, Garcia-Godoy F, Wong DT. Saliva diagnostics - Current views and directions. Exp Biol Med (Maywood) 2016; 242:459-472. [PMID: 27903834 DOI: 10.1177/1535370216681550] [Citation(s) in RCA: 257] [Impact Index Per Article: 28.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
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.
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Affiliation(s)
| | | | - Katri Aro
- 1 School of Dentistry, Center for Oral/Head & Neck Oncology Research, University of California at Los Angeles, Los Angeles, CA 90095, USA
| | - Michael Tu
- 1 School of Dentistry, Center for Oral/Head & Neck Oncology Research, University of California at Los Angeles, Los Angeles, CA 90095, USA
| | - Franklin Garcia-Godoy
- 3 College of Dentistry, University of Tennessee Health Science Center, Bioscience Research Center, Memphis, TN 38163, USA
| | - David Tw Wong
- 1 School of Dentistry, Center for Oral/Head & Neck Oncology Research, University of California at Los Angeles, Los Angeles, CA 90095, USA
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Lorenz TK, Demas GE, Heiman JR. Partnered sexual activity moderates menstrual cycle-related changes in inflammation markers in healthy women: an exploratory observational study. Fertil Steril 2016; 107:763-773.e3. [PMID: 27919440 DOI: 10.1016/j.fertnstert.2016.11.010] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2016] [Revised: 11/09/2016] [Accepted: 11/10/2016] [Indexed: 11/28/2022]
Abstract
OBJECTIVE To examine differences in inflammation markers in sexually active versus abstinent women and observe changes in inflammation markers across the menstrual cycle. Cycle-related immune fluctuations may have evolved to reduce interference with conception. If so, reproductively active (i.e., sexually active) women should show the most variability in cytokine expression. DESIGN Participants provided serum samples at menses and ovulation (from which cytokines were assayed) and saliva samples at menses and during follicular, ovulation, and luteal phases (from which C-reactive protein [CRP] was assayed). Participants self-reported intercourse frequency during the study. SETTING Academic research laboratory. PATIENT(S) Thirty-two healthy, naturally cycling premenopausal women (sexually active, n = 15; abstinent, n = 17). INTERVENTION(S) Observational study. MAIN OUTCOME MEASURE(S) Levels of proinflammatory cytokines (interleukin-6 [IL-6], interferon γ [IFN-γ], tumor necrosis factor-α [TNF-α]), an anti-inflammatory cytokine (interleukin-4 [IL-4]), and a marker of total inflammation (CRP). RESULT(S) Sexually active women had higher levels of all of the immune markers measured, including both pro- and anti-inflammatory cytokines, than abstinent women. Relative to sexually active women, abstinent women had less change across the menstrual cycle in levels of CRP. Among sexually active women, higher intercourse frequency predicted greater midcycle decreases in CRP, IL-6, and IFN-γ and midcycle increases in IL-4. CONCLUSION(S) Sexual activity may stimulate a complex interaction between pro- and anti-inflammatory cytokines that subsequently drives midcycle declines in inflammation.
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Affiliation(s)
- Tierney K Lorenz
- Kinsey Institute, Indiana University, Bloomington, Indiana; Center for Integrative Study for Animal Behavior, Indiana University, Bloomington, Indiana; Department of Psychology, University of North Carolina at Charlotte, Charlotte, North Carolina.
| | - Gregory E Demas
- Center for Integrative Study for Animal Behavior, Indiana University, Bloomington, Indiana; Department of Biology, Indiana University, Bloomington, Indiana
| | - Julia R Heiman
- Kinsey Institute, Indiana University, Bloomington, Indiana; Center for Integrative Study for Animal Behavior, Indiana University, Bloomington, Indiana; Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana
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McRae MP, Bozkurt B, Ballantyne CM, Sanchez X, Christodoulides N, Simmons G, Nambi V, Misra A, Miller CS, Ebersole JL, Campbell C, McDevitt JT. Cardiac ScoreCard: A Diagnostic Multivariate Index Assay System for Predicting a Spectrum of Cardiovascular Disease. EXPERT SYSTEMS WITH APPLICATIONS 2016; 54:136-147. [PMID: 31467464 PMCID: PMC6715313 DOI: 10.1016/j.eswa.2016.01.029] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/09/2023]
Abstract
Clinical decision support systems (CDSSs) have the potential to save lives and reduce unnecessary costs through early detection and frequent monitoring of both traditional risk factors and novel biomarkers for cardiovascular disease (CVD). However, the widespread adoption of CDSSs for the identification of heart diseases has been limited, likely due to the poor interpretability of clinically relevant results and the lack of seamless integration between measurements and disease predictions. In this paper we present the Cardiac ScoreCard-a multivariate index assay system with the potential to assist in the diagnosis and prognosis of a spectrum of CVD. The Cardiac ScoreCard system is based on lasso logistic regression techniques which utilize both patient demographics and novel biomarker data for the prediction of heart failure (HF) and cardiac wellness. Lasso logistic regression models were trained on a merged clinical dataset comprising 579 patients with 6 traditional risk factors and 14 biomarker measurements. The prediction performance of the Cardiac ScoreCard was assessed with 5-fold cross-validation and compared with reference methods. The experimental results reveal that the ScoreCard models improved performance in discriminating disease versus non-case (AUC = 0.8403 and 0.9412 for cardiac wellness and HF, respectively), and the models exhibit good calibration. Clinical insights to the prediction of HF and cardiac wellness are provided in the form of logistic regression coefficients which suggest that augmenting the traditional risk factors with a multimarker panel spanning a diverse cardiovascular pathophysiology provides improved performance over reference methods. Additionally, a framework is provided for seamless integration with biomarker measurements from point-of-care medical microdevices, and a lasso-based feature selection process is described for the down-selection of biomarkers in multimarker panels.
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Affiliation(s)
| | - Biykem Bozkurt
- Michael E. DeBakey VA Medical Center, Houston, TX, USA
- Section of Cardiology, Baylor College of Medicine, Houston, TX, USA
| | | | - Ximena Sanchez
- Department of Bioengineering, Rice University, Houston, TX, USA
- Department of Chemistry, Rice University, Houston, TX, USA
| | - Nicolaos Christodoulides
- Department of Bioengineering, Rice University, Houston, TX, USA
- Department of Chemistry, Rice University, Houston, TX, USA
| | - Glennon Simmons
- Department of Bioengineering, Rice University, Houston, TX, USA
- Department of Chemistry, Rice University, Houston, TX, USA
| | - Vijay Nambi
- Michael E. DeBakey VA Medical Center, Houston, TX, USA
- Section of Cardiology, Baylor College of Medicine, Houston, TX, USA
| | | | - Craig S. Miller
- Department of Oral Health Practice, Center for Oral Health Research, College of Dentistry University of Kentucky, Lexington, KY, USA
| | - Jeffrey L. Ebersole
- Department of Oral Health Practice, Center for Oral Health Research, College of Dentistry University of Kentucky, Lexington, KY, USA
| | - Charles Campbell
- Department of Cardiology, Erlanger Health System, Chattanooga, TN, USA
| | - John T. McDevitt
- Department of Bioengineering, Rice University, Houston, TX, USA
- Department of Chemistry, Rice University, Houston, TX, USA
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McRae MP, Simmons G, McDevitt JT. Challenges and opportunities for translating medical microdevices: insights from the programmable bio-nano-chip. Bioanalysis 2016; 8:905-19. [PMID: 27071710 PMCID: PMC4870725 DOI: 10.4155/bio-2015-0023] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2015] [Accepted: 03/04/2016] [Indexed: 12/11/2022] Open
Abstract
This perspective highlights the major challenges for the bioanalytical community, in particular the area of lab-on-a-chip sensors, as they relate to point-of-care diagnostics. There is a strong need for general-purpose and universal biosensing platforms that can perform multiplexed and multiclass assays on real-world clinical samples. However, the adoption of novel lab-on-a-chip/microfluidic devices has been slow as several key challenges remain for the translation of these new devices to clinical practice. A pipeline of promising medical microdevice technologies will be made possible by addressing the challenges of integration, failure to compete with cost and performance of existing technologies, requisite for new content, and regulatory approval and clinical adoption.
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Affiliation(s)
- Michael P McRae
- Department of Bioengineering, Rice University, Houston, TX, USA
| | - Glennon Simmons
- Department of Biomaterials, New York University, New York, NY, USA
| | - John T McDevitt
- Department of Bioengineering, Rice University, Houston, TX, USA
- Department of Biomaterials, New York University, New York, NY, USA
- Department of Chemistry, Rice University, Houston, TX, USA
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Luppa PB, Bietenbeck A, Beaudoin C, Giannetti A. Clinically relevant analytical techniques, organizational concepts for application and future perspectives of point-of-care testing. Biotechnol Adv 2016; 34:139-60. [DOI: 10.1016/j.biotechadv.2016.01.003] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2015] [Revised: 01/15/2016] [Accepted: 01/17/2016] [Indexed: 01/19/2023]
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Gebauer A, Schmidt S, Hoffmann W. Status and perspective of lab-on-a-chip systems for common diseases: a systematic review from 2003 to 2013. Per Med 2016; 13:71-91. [PMID: 29749869 DOI: 10.2217/pme.15.42] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Lab-on-a-chip systems (LOCs) are a useful aid for the individualization of therapeutic algorithms at the point-of-care. MATERIALS & METHODS We performed a systematic literature review on LOCs for diseases with a global impact for healthcare. RESULTS A total of 1007 articles matched the previously specified search criteria, thereof 65 studies could be included in this review. A total of 55 different LOCs were evaluated, most for diagnosis or monitoring of cancer (n = 24). For other diseases we found considerably less analyzed LOCs. The analytical performance of the LOCs was usually very good, 37 (67%) LOCs had a sensitivity higher than 90%. CONCLUSION Although LOC systems performance has been positively evaluated in the great majority of studies, the testing was mostly limited to the research laboratory setting rather than real-world scenarios.
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Affiliation(s)
- Alexander Gebauer
- Institute for Community Medicine, Section Epidemiology of Healthcare & Community Health, University Medicine Greifswald, Germany
| | - Silke Schmidt
- Institute for Community Medicine, Section Epidemiology of Healthcare & Community Health, University Medicine Greifswald, Germany
| | - Wolfgang Hoffmann
- Institute for Community Medicine, Section Epidemiology of Healthcare & Community Health, University Medicine Greifswald, Germany
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Christodoulides N, De La Garza R, Simmons GW, McRae MP, Wong J, Newton TF, Kosten TR, Haque A, McDevitt JT. Next Generation Programmable Bio-Nano-Chip System for On-Site Detection in Oral Fluids. JOURNAL OF DRUG ABUSE 2015; 1:1-6. [PMID: 26925466 PMCID: PMC4765139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
Current on-site drug of abuse detection methods involve invasive sampling of blood and urine specimens, or collection of oral fluid, followed by qualitative screening tests using immunochromatographic cartridges. Test confirmation and quantitative assessment of a presumptive positive are then provided by remote laboratories, an inefficient and costly process decoupled from the initial sampling. Recently, a new noninvasive oral fluid sampling approach that is integrated with the chip-based Programmable Bio-Nano-Chip (p-BNC) platform has been developed for the rapid (~ 10 minutes), sensitive detection (~ ng/ml) and quantitation of 12 drugs of abuse. Furthermore, the system can provide the time-course of select drug and metabolite profiles in oral fluids. For cocaine, we observed three slope components were correlated with cocaine-induced impairment using this chip-based p-BNC detection modality. Thus, this p-BNC has significant potential for roadside drug testing by law enforcement officers. Initial work reported on chip-based drug detection was completed using 'macro' or "chip in the lab" prototypes, that included metal encased "flow cells", external peristaltic pumps and a bench-top analyzer system instrumentation. We now describe the next generation miniaturized analyzer instrumentation along with customized disposables and sampling devices. These tools will offer real-time oral fluid drug monitoring capabilities, to be used for roadside drug testing as well as testing in clinical settings as a non-invasive, quantitative, accurate and sensitive tool to verify patient adherence to treatment.
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Affiliation(s)
- Nicolaos Christodoulides
- Department of Bioengineering, Rice University, Houston TX, USA
- Department of Chemistry, Rice University, Houston TX, USA
| | - Richard De La Garza
- Menninger Department of Psychiatry & Behavioral Sciences, Baylor College of Medicine, Houston TX, USA
- Department of Pharmacology, Baylor College of Medicine, Houston TX, USA
- Department of Neuroscience, Baylor College of Medicine, Houston TX, USA
- Department of Veterans Affairs Medical Center, Houston, TX, USA
| | - Glennon W Simmons
- Department of Bioengineering, Rice University, Houston TX, USA
- Department of Chemistry, Rice University, Houston TX, USA
| | - Michael P McRae
- Department of Bioengineering, Rice University, Houston TX, USA
| | - Jorge Wong
- Department of Bioengineering, Rice University, Houston TX, USA
- Department of Chemistry, Rice University, Houston TX, USA
| | - Thomas F Newton
- Menninger Department of Psychiatry & Behavioral Sciences, Baylor College of Medicine, Houston TX, USA
- Department of Pharmacology, Baylor College of Medicine, Houston TX, USA
- Department of Veterans Affairs Medical Center, Houston, TX, USA
| | - Thomas R. Kosten
- Menninger Department of Psychiatry & Behavioral Sciences, Baylor College of Medicine, Houston TX, USA
- Department of Pharmacology, Baylor College of Medicine, Houston TX, USA
- Department of Neuroscience, Baylor College of Medicine, Houston TX, USA
- Department of Veterans Affairs Medical Center, Houston, TX, USA
| | - Ahmed Haque
- Department of Bioengineering, Rice University, Houston TX, USA
| | - John T McDevitt
- Department of Bioengineering, Rice University, Houston TX, USA
- Department of Chemistry, Rice University, Houston TX, USA
- Department of Biomaterials, Bioengineering Institute, New York University, New York, NY, USA
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Vashist SK, Luppa PB, Yeo LY, Ozcan A, Luong JH. Emerging Technologies for Next-Generation Point-of-Care Testing. Trends Biotechnol 2015; 33:692-705. [DOI: 10.1016/j.tibtech.2015.09.001] [Citation(s) in RCA: 501] [Impact Index Per Article: 50.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2015] [Revised: 08/27/2015] [Accepted: 09/08/2015] [Indexed: 12/21/2022]
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Xiao H, Langerman A, Zhang Y, Khalid O, Hu S, Cao CX, Lingen MW, Wong DT. Quantitative proteomic analysis of microdissected oral epithelium for cancer biomarker discovery. Oral Oncol 2015; 51:1011-1019. [DOI: 10.1016/j.oraloncology.2015.08.008] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2015] [Revised: 08/11/2015] [Accepted: 08/13/2015] [Indexed: 10/23/2022]
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McRae MP, Simmons GW, Wong J, Shadfan B, Gopalkrishnan S, Christodoulides N, McDevitt JT. Programmable bio-nano-chip system: a flexible point-of-care platform for bioscience and clinical measurements. LAB ON A CHIP 2015; 15:4020-31. [PMID: 26308851 PMCID: PMC4589532 DOI: 10.1039/c5lc00636h] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/22/2023]
Abstract
The development of integrated instrumentation for universal bioassay systems serves as a key goal for the lab-on-a-chip community. The programmable bio-nano-chip (p-BNC) system is a versatile multiplexed and multiclass chemical- and bio-sensing system for bioscience and clinical measurements. The system is comprised of two main components, a disposable cartridge and a portable analyzer. The customizable single-use plastic cartridges, which now can be manufactured in high volumes using injection molding, are designed for analytical performance, ease of use, reproducibility, and low cost. These labcard devices implement high surface area nano-structured biomarker capture elements that enable high performance signaling and are index-matched to real-world biological specimens. This detection modality, along with the convenience of on-chip fluid storage in blisters and self-contained waste, represents a standard process to digitize biological signatures at the point-of-care. A companion portable analyzer prototype has been developed to integrate fluid motivation, optical detection, and automated data analysis, and it serves as the human interface for complete assay automation. In this report, we provide a systems-level perspective of the p-BNC universal biosensing platform with an emphasis on flow control, device integration, and automation. To demonstrate the flexibility of the p-BNC, we distinguish diseased and non-case patients across three significant disease applications: prostate cancer, ovarian cancer, and acute myocardial infarction. Progress towards developing a rapid 7 minute myoglobin assay is presented using the fully automated p-BNC system.
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Affiliation(s)
| | - Glennon. W. Simmons
- Department of Bioengineering, Rice University, Houston, TX, U.S.A
- Department of Chemistry, Rice University, Houston, TX, U.S.A
| | - Jorge Wong
- Department of Bioengineering, Rice University, Houston, TX, U.S.A
- Department of Chemistry, Rice University, Houston, TX, U.S.A
| | - Basil Shadfan
- Department of Chemistry, Rice University, Houston, TX, U.S.A
| | | | - Nicolaos Christodoulides
- Department of Bioengineering, Rice University, Houston, TX, U.S.A
- Department of Chemistry, Rice University, Houston, TX, U.S.A
- Department of Biomaterials and Biomimetics, New York University College of Dentistry, New York, NY, U.S.A
| | - John T. McDevitt
- Department of Bioengineering, Rice University, Houston, TX, U.S.A
- Department of Chemistry, Rice University, Houston, TX, U.S.A
- Department of Biomaterials and Biomimetics, New York University College of Dentistry, New York, NY, U.S.A
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50
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Christodoulides N, De La Garza R, Simmons GW, McRae MP, Wong J, Newton TF, Smith R, Mahoney JJ, Hohenstein J, Gomez S, Floriano PN, Talavera H, Sloan DJ, Moody DE, Andrenyak DM, Kosten TR, Haque A, McDevitt JT. Application of programmable bio-nano-chip system for the quantitative detection of drugs of abuse in oral fluids. Drug Alcohol Depend 2015; 153:306-13. [PMID: 26048639 PMCID: PMC4509839 DOI: 10.1016/j.drugalcdep.2015.04.026] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2014] [Revised: 03/27/2015] [Accepted: 04/22/2015] [Indexed: 10/23/2022]
Abstract
OBJECTIVE There is currently a gap in on-site drug of abuse monitoring. Current detection methods involve invasive sampling of blood and urine specimens, or collection of oral fluid, followed by qualitative screening tests using immunochromatographic cartridges. While remote laboratories then may provide confirmation and quantitative assessment of a presumptive positive, this instrumentation is expensive and decoupled from the initial sampling making the current drug-screening program inefficient and costly. The authors applied a noninvasive oral fluid sampling approach integrated with the in-development chip-based Programmable bio-nano-chip (p-BNC) platform for the detection of drugs of abuse. METHOD The p-BNC assay methodology was applied for the detection of tetrahydrocannabinol, morphine, amphetamine, methamphetamine, cocaine, methadone and benzodiazepines, initially using spiked buffered samples and, ultimately, using oral fluid specimen collected from consented volunteers. RESULTS Rapid (∼10min), sensitive detection (∼ng/mL) and quantitation of 12 drugs of abuse was demonstrated on the p-BNC platform. Furthermore, the system provided visibility to time-course of select drug and metabolite profiles in oral fluids; for the drug cocaine, three regions of slope were observed that, when combined with concentration measurements from this and prior impairment studies, information about cocaine-induced impairment may be revealed. CONCLUSIONS This chip-based p-BNC detection modality has significant potential to be used in the future by law enforcement officers for roadside drug testing and to serve a variety of other settings, including outpatient and inpatient drug rehabilitation centers, emergency rooms, prisons, schools, and in the workplace.
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Affiliation(s)
- Nicolaos Christodoulides
- Department of Bioengineering, Rice University, Houston TX.,Department of Chemistry, Rice University, Houston TX
| | - Richard De La Garza
- Menninger Department of Psychiatry & Behavioral Sciences, Baylor College of Medicine, Houston TX.,Department of Pharmacology, Baylor College of Medicine, Houston TX.,Department of Neuroscience, Baylor College of Medicine, Houston TX
| | - Glennon W. Simmons
- Department of Bioengineering, Rice University, Houston TX.,Department of Chemistry, Rice University, Houston TX
| | | | - Jorge Wong
- Department of Bioengineering, Rice University, Houston TX.,Department of Chemistry, Rice University, Houston TX
| | - Thomas F. Newton
- Menninger Department of Psychiatry & Behavioral Sciences, Baylor College of Medicine, Houston TX.,Department of Pharmacology, Baylor College of Medicine, Houston TX.,Department of Veterans Affairs Medical Center, Houston, TX
| | - Regina Smith
- Department of Bioengineering, Rice University, Houston TX
| | - James J. Mahoney
- Menninger Department of Psychiatry & Behavioral Sciences, Baylor College of Medicine, Houston TX
| | | | - Sobeyda Gomez
- Department of Bioengineering, Rice University, Houston TX
| | - Pierre N. Floriano
- Department of Bioengineering, Rice University, Houston TX.,Department of Chemistry, Rice University, Houston TX
| | | | | | - David E. Moody
- Center for Human Toxicology, Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT
| | - David M. Andrenyak
- Center for Human Toxicology, Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT
| | - Thomas R. Kosten
- Menninger Department of Psychiatry & Behavioral Sciences, Baylor College of Medicine, Houston TX.,Department of Pharmacology, Baylor College of Medicine, Houston TX.,Department of Neuroscience, Baylor College of Medicine, Houston TX.,Department of Veterans Affairs Medical Center, Houston, TX
| | - Ahmed Haque
- Department of Bioengineering, Rice University, Houston TX
| | - John T. McDevitt
- Department of Bioengineering, Rice University, Houston TX.,Department of Chemistry, Rice University, Houston TX.,Department Biomaterials, Bioengineering Institute, New York University, 433 First Avenue, Room 820, New York, NY 10010-4086, USA,Send correspondence to: John T. McDevitt, Chair, Department Biomaterials, Bioengineering Institute, New York University, 433 First Avenue, Room 820, New York, NY 10010-4086, USA, , Phone: 212-998-9204
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