“Innovative Technological Approaches for validation of Salivary AGEs as novel biomarkers in evaluation of risk factors in diet-related diseases”
|Partner Organization||Partner Country|
|University of Medicine and Pharmacy Iuliu Hatieganu Cluj||ROMANIA|
|University of Oviedo||SPAIN|
|National University of Ireland Galway||IRELAND|
|Technische Universitaet Dresden||GERMANY|
1. Overall project description
Recent findings convincingly demonstrate that Advanced Glycation End Products (AGEs) are modifiable by diet and reflect changes in healthy state. SALIVAGES investigates whether that diet-induced AGEs can act as reliable biomarkers of changes in health status and/or risk, focusing on the most highly accessible source of AGEs, the saliva. The main objectives of SALIVAGES were
the development of innovative and original tools for assessing status and efficacy of interventions, namely biosensors, metabolomics and biomimic approaches.
The investigation on the role of salivary AGEs as early and easily accessible biomarkers of changes in health status and/or the risk of developing diet-related diseases.
The following results have been obtained:
We developed in vivo models suitable for studying diet-induced AGEs production;
We identified the mechanistic link between AGEs overproduction and excessive inflammatory response and oxidative stress;
We characterized and validated AGEs and inflammatory-related products as biomarkers in experimental models of metabolic diseases by metabolomics approaches integrated with advanced fingerprinting methods for analytes separation/identification;
We explored salivary volatilome to reveal informative features correlated with AGEs distribution;
We investigated glycosylation changes in biological samples in response to AGEs and thereby potentially identify putative glyco-biomarkers using innovative methods for glycomic analyses;
We developed innovative technologies of biosensors for the salivary detection of AGEs;
We performed comparative evaluation of AGEs and related biomarkers in human saliva and serum.
The main impacts of the projects are here summarized:
New rapid and robust methods for analyses of salivary samples developed within this project that are now available and under investigation within other context of health monitoring.
A new biobank of salivary samples is now available and it can offer interesting stratified samples for studying the influence of diet on the health status of the subjects.
A new international partnership among members of the consortium documented by several papers with joint authorship, lab rotation activities and further joint grant applications.
The most important result is the validation of salivary AGEs as reliable early and non-invasive markers of health status and the following development of either electrochemical and optical prototypes of biosensors for AGEs detection. Our research results strengthen the perspective of the need of new, non-invasive approaches to the monitoring of health conditions and diet-induced changes in health status, for improving health care and clinical outcomes.
So far the papers we reported with acknowledgement of SALIVAGES are the following ones:
- Arch Oral Biol. 2018 doi: 10.1016/j.archoralbio.2018.05.013. PMID: 29803117
- Oxid Med Cell Longev. 2018 doi: 10.1155/2018/5042428. PMID: 30327714
- Curr Trends Biomedical Eng & Biosci 2018 DOI: 10.19080/CTBEB.2019.17.555969
- Biomark Med 2019, doi: 10.2217/bmm-2018-0448. PMID: 30968701
- Food Science & Nutrition 2019 https://doi.org/10.1002/fsn3.950
- Trends Analytical Chemistry 2019 https://doi.org/10.1016/j.trac.2019.02.020.
- Electroanalysis 2019 doi: 10.1002/elan.201800620.
- Biosensors 2019 doi: 10.3390/bios9010027
- Biochem Mol Biol J 2019 DOI: 10.21767/2471-8084.100061
- Materials 2019 doi:10.3390/ma12071180
- Eur J Oral Sci 2019 doi: 10.1111/eos.12625
- J Mind Med Sci. 2019 doi: 10.1007/s10856-019-6227-9
- Sensors 2019 https://doi.org/10.1016/j.snb.2018.10.096.
- Current Directions in Biomedical Engineering 2019
- PLoS One 2019 (10.1371/journal.pone.0220208, PMID: 31532774)
- Antioxidants 2020, doi: 10.3390/antiox9020142. PMID: 32041293
- Biophotonics in Point-of-Care 2020 https://doi.org/10.1117/12.2555956
- Mol Metab. 2020 doi: 10.1016/j.molmet.2020.101009.
Further cooperative publications are in preparation.
4.1 List of publications
|Authors||Title||Year, Issue, PP||Partners Number||Doi|
|Aranka Ilea, Anida M. Băbţan, Bianca A. Boşca, Maria Crişan, Nausica B. Petrescu, Massimo Collino, Rosa M. Sainz, Jared Q. Gerlach, Radu Septimiu Câmpian.(partners involved: University of Medicine and Pharmacy ”Iuliu Hațieganu” Cluj-Napoca, RO University of Turin, IT University of Oviedo, SP National University of Ireland Galway, IR)||Advanced glycation end products (AGEs) in oral pathology.||2018 93 22||https://doi.org/10.1016/j.archoralbio.2018.05.013||Download|
|Băbţan AM, Ilea A, Boşca BA, Crişan M, Petrescu NB, Collino M, Sainz RM, Gerlach JQ, Câmpian RS. (prtners involved: University of Medicine and Pharmacy ”Iuliu Hațieganu” Cluj-Napoca, RO University of Turin, IT University of Oviedo, SP National University of Ireland Galway, IR)||Advanced glycation end products as biomarkers in systemic diseases: premises and perspectives of salivary advanced glycation end products.||2019||doi: 10.2217/bmm-2018-0448.||Download|
|Collotta D, Lucarini L, Chiazza F, Cento AS, Durante M, Sgambellone S, Chini J, Baratta F, Aragno M, Mastrocola R, Masini E, Collino M. (Partner involved: University of Turin, IT )||Reduced Susceptibility to Sugar-Induced Metabolic Derangements and Impairments of Myocardial Redox Signaling in Mice Chronically Fed with D-Tagatose when Compared to Fructose.||2018||doi: 10.1155/2018/5042428.||Download|
|Feeney, S., Gerlach, J. Q., Slattery, H., Kilcoyne, M., Hickey, R. M., & Joshi, L. (Partner involved National University of Ireland Galway, IE)||Lectin microarray profiling and monosaccharide analysis of bovine milk immunoglobulin G oligosaccharides during the first 10 days of lactation||2019||https://doi.org/10.1002/fsn3.950||Download|
|Tertis M., Melinte G., Ciui B.C., Simon I., Stiufiuc R., Sandulescu R., Cristea C. (Partner involved University of Medicine and Pharmacy ”Iuliu Hațieganu” Cluj-Napoca, RO)||A Novel Label Free Electrochemical Magnetoimmunosensor for Human Interleukin-6 Quantification in Serum,||2019 31 282||10.1002/elan.201800620.||Download|
|Tiuca Gug I., Tertis M., Hosu O., Cristea C., (Partner involved University of Medicine and Pharmacy ”Iuliu Hațieganu” Cluj-Napoca, RO)||Salivary biomarkers detection: Analytical and immunological methods overview,||2019 113 301||https://doi.org/10.1016/j.trac.2019.02.020.||Download|
|Ciui B, Tertis M, Feurdean C, Ilea A, Sandulescu R, Wang J, Cristea C, (Partner involved University of Medicine and Pharmacy ”Iuliu Hațieganu” Cluj-Napoca, RO)||Cavitas electrochemical sensor toward detection of N-epsilon(Carboxymethyl)lysine in oral cavity,||2019 281 399||https://doi.org/10.1016/j.snb.2018.10.096.||Download|
|Ilea A, Andrei V, Feurdean CN, Băbțan AM, Petrescu NB, Câmpian RS, Boșca AB, Ciui B, Tertiș M, Săndulescu R, Cristea C. (Partner involved University of Medicine and Pharmacy ”Iuliu Hațieganu” Cluj-Napoca, RO)||Saliva, a Magic Biofluid Available for Multilevel Assessment and a Mirror of General Health-A Systematic Review.||2019 9||Download|
|Aranka Ilea1, Adela Cristina Lazăr, Andreeas-Vasile Bojor, Georgeta Victoria Inceu, Anca Ștefania Mesaros, Radu Septimiu Câmpian, Anida-Maria Băbțan, Nausica Bianca Petrescu and Adina Bianca Boșca (Partner involved University of Medicine and Pharmacy ”Iuliu Hațieganu” Cluj-Napoca, RO)||Oral Health Status in a Group of Patients with Type 2 Diabetes Mellitus||10.19080/CTBEB.2019.17.555969||Download|
|Petrescu Bianca Nausica, Băbțan Anida-Maria, Olga Sorițău, Buhățel Dan, Ionel Anca, Feurdean Nicoleta Claudia, Boșca Adina Bianca, Câmpian Radu Septimiu, Ilea Aranka. (Partner involved University of Medicine and Pharmacy ”Iuliu Hațieganu” Cluj-Napoca, RO)||Stem Cells in Head and Neck Cancers Pathogenesis: Are Advanced Glycation End Products (AGEs) Involved?||2019 4||DOI: 10.21767/2471-8084.100061||Download|
|Mastrocola R, Ferrocino I, Liberto E, Chiazza F, Cento AS, Collotta D, Querio G, Nigro D, Bitonto V, Cutrin JC, Rantsiou K, Durante M, Masini E, Aragno M, Cordero C, Cocolin L, Collino M (Partner involved University of Turin)||Fructose liquid and solid formulations differently affect gut integrity, microbiota composition and related liver toxicity: a comparative in vivo study||10.1016/j.jnutbio.2018.02.003||Download|
|Bressanello D, Liberto E, Collino M, Chiazza F, Mastrocola R, Reichenbach SE, Bicchi C, Cordero C (Project Partner involved UNiversity ot Turin)||Combined untargeted and targeted fingerprinting by comprehensive two-dimensional gas chromatography: revealing fructose-induced changes in mice urinary metabolic signatures||10.1007/s00216-018-0950-9||Download|
4.2 Presentation of the project
|Target group||Authors||Means of communication||Hyperlink|
|scientists||Adina Bianca Boșca, Marian Tăulescu, Viorel Miclăuș, Anida Maria Băbțan, Aranka Ilea. Accumulation of N-epsilon carboxymethyl lysine in rat oral cavity tissues: a biomarker of aging. 23rd BaSS Congress, Dental Medicine of the Younger vs. Elderly Patients, 10 – 12 May 2018, PALAS Congress Hall, IASI, ROMANIA, pp. 55||Oral presentation|
|scientists||Cento Alessia S.; Chiazza F; Collotta D; Barutta F; Aragno M; Scheijen J; Collino M, Gaens KH; Schalkwijk CG; Wouters K; Mastrocola R. Genetic deletion of RAGE in Dbdb mice interferes with AGEs receptors and detoxifying systems in liver. Conference: 19th Biennial Meeting of the Society-for-Free-Radical-Research-International (SFRRI) Location: Lisbon, PORTUGAL Date: 2018||Oral presentation|
|scientists||Chiara Cordero,1*Erica Liberto1, Fausto Chiazza1, Raffaella Mastrocola2, Stephen E. Reichenbach3, Carlo Bicchi1 and Massimo Collino SALIVAGE: The “form” makes the difference: unrevealing the differential impact of liquid and solid fructose in mice urinary metabolic signatures by comprehensive two-dimensional gas chromatography XII Italian Food Chemistry Congress (Camerino, September 24-27 2018)||Oral presentation|
|scientists||Jared Gerlach, Raffaella Mastrocola, Erica Liberto, Chiara Cordero, Massimo Collino and Lokesh Joshi SALIVAGES: Lectin microarray-based investigation of diet dependent, differential glycosylation of proteins in murine biological fluids and organ homogenates XII Italian Food Chemistry Congress (Camerino, September 24-27 2018)||Oral presentation|
|scientists||Hellwig M, Manig F, Pietz F, Henle T: Salivary methionine sulfoxide as a marker for oxidative stress. International Conference on Oxidative Stress Reduction, Redox Homeostasis and Antioxidants - Redox 2018, Paris, June 25-26 2018||Oral presentation|
|scientists||Manig F, Hellwig M, Pietz F, Henle T: Surveying the salivary AGEom - quantitation of glycation compounds in saliva and the dietary impact of an AGE-rich diet. 13. International Symposium on the Maillard Reaction, Montreal, September 10-14 2018 Chiara Cordero, Marta Cialiè Rosso, Erica Liberto, Massimo Collino, Gianluca Aimaretti, Paolo Marzullo, Chiara Mele, Stephen E. Reichenbach, Qingping Tao, Carlo Bicchi (2018). EXPLORING “EXTRA-DIMENSIONS” TO CAPTURE METABOLITE FINGERPRINTS IN METABOLICALLY HEALTHY AND UNHEALTHY OBESE PATIENTS BY GC×GC TANDEM IONIZATION-TOFMS. In: Abstract Book. p. 16, Messina Italia:Luigi Mondello and Paola Dugo, ISBN: 978-88-941816-1-6, Riva del Garda (TN) Italia, May 13 – 18, 2018||Oral presentation|
|scientists||Hellwig M, Manig F, Henle T: Yeast metabolites of glycated amino acids in beer – potential biomarkers in saliva and urine? XII Italian Food Chemistry Congress, Camerino, September 24-27 2018||Oral presentation|
|scientists||Adina Bianca Bosca, Marian Tăulescu, Viorel Miclăuş, Mihai Negru, Anida Maria Babtan, Nausica Bianca Petrescu, Anca Mesaros, Cristina Gasparik, Alexandra Irimie, Alina Elena Pârvu, Maria Crişan, Aranka Ilea. ACCUMULATION OF N-EPSILON CARBOXYMETHYL LYSINE IN RAT ORAL CAVITY TISSUES AND ORGANS CORRELATED WITH AGING. International Symposium: Health through education, prevention and treatment, 7-8 December, 2018, Cluj-Napoca, Romania Anida-Maria Babtan, Aranka Ilea, Nausica Petrescu, Bianca Bosca, Maria Crișan, Manuela Lenghel, Anca Ionel, Andreea Pop, Willi Uriciuc, Codruta Mirica, Claudia Feurdean, Radu Septimiu Campian. ADVANCED GLYCATION END PRODUCTS (AGEs) ULTRASOUND EVALUATION IN FACIAL SKIN AND MUCOSA. International Symposium: Health through education, prevention and treatment, 7-8 December, 2018, Cluj-Napoca, Romania||Oral presentation|
|scientists||Boșca Adina Bianca, Șovrea Alina Simona, Miclăuș Viorel, Ruxanda Flavia, Mihu Carmen Mihaela, Melincovici Carmen, Constantin Anne Marie, Buhățel Dan, Băbțan Anida-Maria, Petrescu Bianca Nausica, Câmpian Radu Septimiu, Pârvu Alina Elena, Ilea Aranka. New data concerning the origin and activity of the multinucleated giant cells in oral cavity granulomas. The XVIth National Symposium on Microscopic Morphology with International Participation, Craiova 23-26 May 2018, Abstract Summaries pp. 26-27||Oral presentation|
|scientists||Willi A. Uriciuc, Aranka Ilea, Horatiu Vermeșan, Radu Septimiu Câmpian. Research about different methods in dental alloys casting structures. Napoca Biodent Symposium 8th Edition, Dentistry – from research to practice, 25-26 May, 2018, Cluj-Napoca, Romania||Oral presentation|
|scientists||Collino M, Liberto E, Mastrocola R, Ferrocino I, Chiazza F, Cento AS, Collotta D, Rantsiou K, Ilea A, Aragno M, Cocolin L, Bicchi C, Cordero C. The “form” makes the difference: unrevealing the differential susceptibility to sugar-induced metabolic derangements evoked by liquid and solid fructose formulations. EuroNutrition 2018. Annual Congress on Nutrition & Healthcare, October 18-20, 2018 Paris, France||Invited Talk|
|scientists||M. Collino “Innovative Technological Approaches for validation of Salivary AGEs as novel biomarkers in evaluation of risk factors in diet-related diseases” EuroNutrition 2018. Annual Congress on Nutrition & Healthcare, October 18-20, 2018 Paris, France||Invited Talk|
|scientists||Liberto E*, Cordero C, Mastrocola R, Ferrocino I, Chiazza F, Cento AS, Collotta D, Rantsiou K, Aragno M1, Cocolin L, Bicchi C and Collino M SALIVAGE: The “form” makes the difference: comprehensive two‐dimensional gas chromatography as highly informative fingerprinting tool to study the impact of fructose formulation on mice’s microbiota and its volatile metabolome signatures XII Italian Food Chemistry Congress (Camerino, September 24-27 2018)||Poster presentation|
|scientists||Manig F, Pietz F, Hellwig M, Henle T: Surveying the salivary AGEome - quantitation of glycation compounds in saliva and the impact of an AGE-rich diet. XII Italian Food Chemistry Congress, Camerino, September 24-27 2018||Poster presentation|
|scientists||Manig F, Pietz F, Hellwig M, Henle T: AGEs in saliva: indication for the metabolic fate of Maillard reaction products in vivo. 47. German Food Chemistry Congress, Berlin, September 17-19 2018||Poster presentation|
|scientists||Adina Bianca Boșca, Marian Tăulescu, Viorel Miclăuș, Mihai Negru, Anida Maria Băbțan, Nausica Bianca Petrescu, Dan Buhățel, Anca Mesaros, Cristina Gasparik, Alexandra Irimie, Alina Elena Parvu, Maria Crișan, Massimo Collino, Aranka Ilea. Expression of N-epsilon carboxymethyl lysine in rat oral cavity tissues and organs: a biomarker of aging. CHIMALI, XII Italian Food Chemistry Congress, Camerino, Italy, September 24-27, 2018||Poster presentation|
|scientists||IlAnida-Maria Băbţan, Aranka Ilea, Nausica Petrescu, Bianca Boşca, Maria Crişan, Manuela Lenghel, Anca Ionel, Dan Buhăţel, Arin Sava, Andreea Pop, Willi Uriciuc, Codruţa Mirica, Claudia Feurdean, Radu Septimiu Câmpian. EVALUATION OF AGEs AT THE SKIN AND MUCOSA LEVELS IN THE OROMAXILOFACIAL AREA THROUGH ULTRASOUNDS. Days of "Iuliu Haţieganu" University of Medicine and Pharmacy Cluj-Napoca, 7 December, 2018, Cluj-Napoca, Romania, p. 88ea Aranka, Crișan Maria, Boșca Adina Bianca, Constantin Anne-Marie, Băbțan Anida Maria, Petrescu Nausica Bianca, Buhățel Dan, Ionel Anca, Câmpian Radu Septimiu. High frequency ultrasound assessment in cutaneous senescence process. CHIMALI, XII Italian Food Chemistry Congress, Camerino, Italy, September 24-27, 2018||Poster presentation|
|scientists||Claudia Feurdean, Aranka Ilea, Ondine Lucaciu, Anca Ionel, Dan Buhajel, Arin Sava, Nausica Petrescu, Adina Sirbu, Andreea Pop, Roxana Bordea, Willi Uriciuc, Codruta Mirica, Anida-Maria Băbţan, Radu Septimiu Câmpian. INSERTION OF SALIVARY BIOSESORS IN DENTAL PROSTHESES. Days of "Iuliu Haţieganu" University of Medicine and Pharmacy Cluj-Napoca, 7 December, 2018, Cluj-Napoca, Romania, p. 90||Poster presentation|
|scientists||Boșca Adina Bianca, Dinte Elena, Ilea Aranka, Muntean Dana, Tomuta Ioan, Hangan Dana, Pârvu Alina Elena, Mihu Carmen Mihaela, Melincovici Carmen, Șovrea Alina, Constantin Anne Marie, Băbțan Anida, Petrescu Nausica, Câmpian Radu Septimiu. Clinical efficacy of a mucoadhesive nanoparticulate gel based on antibiotics, anti-inflammatory drugs and anthocyanins used in the periodontal treatment. The 22nd International Exhibition of INVENTICS – ”INVENTICA 2018” Iași, 27-29 June 2018, Iași, Romania||Poster presentation|
|scientists||V Cepas, F Manig, R Matesanz, M Hellwig, T Henle, RM Sainz: Some dietary Advanced Glycation Endproducts (AGEs) reduce cell viability and produce Reactive Oxygen Species. XII Italian Food Chemistry Congress (CHIMALI 2018). Camerino (Italy) Sept 2018||Poster presentation|
|scientists||V Cepas, R Matesanz, F Manig, M Hellwig, T Henle, RM Sainz: Dietary Glycation Endproducts (AGEs) are cytotoxic for keratinocytes. 41 Congreso de la Sociedad Española de Bioquímica y Biología Molecular. Santander (Spain) Sept 2018||Poster presentation|
|Students (Professional training school)||Vanesa Cepas. Sugars and metabolic disorders. Internatinal Day of Women and Girls in Science. Professional training school CIFP Avilés (Spain) February 2019||Oral presentation|
|Students (Elementary School)||Vanesa Cepas. From science to the table. What molecules are we eating in our foods? International Day of Women and Girls in Science. Elementary School San Pedro de Los Arcos. Oviedo (Spain) February 2019||Oral presentation|
|Students (Secondary School)||Vanesa Cepas. Sugar and metabolic disorders. Secondary School Virgen de La Luz. Avilés (Spain) November 2018||Oral presentation|
4.3 List of submitted patents and other outputs
|Patent licence||Partners involved||Year||International eu or national patent||Comment|