93 results on '"Gradinaru D"'
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2. ESTUDOS EM ANDAMENTO FASE IB E IIA: CROSSWALK-A E CROSSWALK-C, RANDOMIZADOS E CONTROLADOS POR PLACEBO - CROVALIMABE NO TRATAMENTO E PREVENÇÃO DE EPISÓDIOS VASO-OCLUSIVOS NA DOENÇA FALCIFORME
- Author
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Salvino, MA, primary, Antmen, B, additional, Asirwa, FC, additional, Chonat, S, additional, Franceschi, L, additional, Eleftheriou, P, additional, Inati, A, additional, Mahlangu, J, additional, Nur, E, additional, Payá-Pernía, S, additional, Charania, A, additional, Gradinaru, D, additional, Hsia, A, additional, Perretti, T, additional, Sreckovic, S, additional, and Bartolucci, P, additional
- Published
- 2023
- Full Text
- View/download PDF
3. Circulating cell-free DNA in health and disease:the relationship to health behaviours, ageing phenotypes and metabolomics
- Author
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Kananen, L. (Laura), Hurme, M. (Mikko), Buerkle, A. (Alexander), Moreno-Villanueva, M. (Maria), Bernhardt, J. (Jurgen), Debacq-Chainiaux, F. (Florence), Grubeck-Loebenstein, B. (Beatrix), Malavolta, M. (Marco), Basso, A. (Andrea), Piacenza, F. (Francesco), Collino, S. (Sebastiano), Gonos, E. S. (Efstathios S.), Sikora, E. (Ewa), Gradinaru, D. (Daniela), Jansen, E. H. (Eugene H. J. M.), Dolle, M. E. (Martijn E. T.), Salmon, M. (Michel), Stuetz, W. (Wolfgang), Weber, D. (Daniela), Grune, T. (Tilman), Breusing, N. (Nicolle), Simm, A. (Andreas), Capri, M. (Miriam), Franceschi, C. (Claudio), Slagboom, E. (Eline), Talbot, D. (Duncan), Libert, C. (Claude), Raitanen, J. (Jani), Koskinen, S. (Seppo), Härkänen, T. (Tommi), Stenholm, S. (Sari), Ala-Korpela, M. (Mika), Lehtimäki, T. (Terho), Raitakari, O. T. (Olli T.), Ukkola, O. (Olavi), Kähönen, M. (Mika), Jylhä, M. (Marja), Jylhävä, J. (Juulia), Kananen, L. (Laura), Hurme, M. (Mikko), Buerkle, A. (Alexander), Moreno-Villanueva, M. (Maria), Bernhardt, J. (Jurgen), Debacq-Chainiaux, F. (Florence), Grubeck-Loebenstein, B. (Beatrix), Malavolta, M. (Marco), Basso, A. (Andrea), Piacenza, F. (Francesco), Collino, S. (Sebastiano), Gonos, E. S. (Efstathios S.), Sikora, E. (Ewa), Gradinaru, D. (Daniela), Jansen, E. H. (Eugene H. J. M.), Dolle, M. E. (Martijn E. T.), Salmon, M. (Michel), Stuetz, W. (Wolfgang), Weber, D. (Daniela), Grune, T. (Tilman), Breusing, N. (Nicolle), Simm, A. (Andreas), Capri, M. (Miriam), Franceschi, C. (Claudio), Slagboom, E. (Eline), Talbot, D. (Duncan), Libert, C. (Claude), Raitanen, J. (Jani), Koskinen, S. (Seppo), Härkänen, T. (Tommi), Stenholm, S. (Sari), Ala-Korpela, M. (Mika), Lehtimäki, T. (Terho), Raitakari, O. T. (Olli T.), Ukkola, O. (Olavi), Kähönen, M. (Mika), Jylhä, M. (Marja), and Jylhävä, J. (Juulia)
- Abstract
Circulating cell-free DNA (cf-DNA) has emerged as a promising biomarker of ageing, tissue damage and cellular stress. However, less is known about health behaviours, ageing phenotypes and metabolic processes that lead to elevated cf-DNA levels. We sought to analyse the relationship of circulating cf-DNA level to age, sex, smoking, physical activity, vegetable consumption, ageing phenotypes (physical functioning, the number of diseases, frailty) and an extensive panel of biomarkers including blood and urine metabolites and inflammatory markers in three human cohorts (N = 5385; 17‐82 years). The relationships were assessed using correlation statistics, and linear and penalised regressions (the Lasso), also stratified by sex. cf-DNA levels were significantly higher in men than in women, and especially in middle-aged men and women who smoke, and in older more frail individuals. Correlation statistics of biomarker data showed that cf-DNA level was higher with elevated inflammation (C-reactive protein, interleukin-6), and higher levels of homocysteine, and proportion of red blood cells and lower levels of ascorbic acid. Inflammation (C-reactive protein, glycoprotein acetylation), amino acids (isoleucine, leucine, tyrosine), and ketogenesis (3-hydroxybutyrate) were included in the cf-DNA level-related biomarker profiles in at least two of the cohorts. In conclusion, circulating cf-DNA level is different by sex, and related to health behaviour, health decline and metabolic processes common in health and disease. These results can inform future studies where epidemiological and biological pathways of cf-DNA are to be analysed in details, and for studies evaluating cf-DNA as a potential clinical marker.
- Published
- 2023
4. Oxidative stress and xenobiotic detoxification enzymes in rat astrocytes: Correlations with brain aging
- Author
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Gradinaru, D., Minn, A. L., Artur, Y., and Heydel, - M. J.
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- 2013
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5. Inhibition of serum lipid and LDL oxidation by Gerovital H3
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Borsa, C., Prada, G. I., Ionescu, C., Margina, D., and Gradinaru, D.
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- 2013
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6. Psychometric properties of the Romanian version of the borderline personality questionnaire in a sample of nonclinical adults
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Grădinaru Diana, Constantin Ticu, and Sorin Candel Octav
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borderline personality disorder ,borderline personality questionnaire ,psychometric properties ,nonclinical sample ,romania ,Psychology ,BF1-990 - Abstract
People with borderline personality disorder (BPD) feel instability in self-image, affects and relationships. The current study aimed to examine the psychometric properties of the Borderline Personality Questionnaire (BPQ) in a sample of 737 nonclinical Romanian adults. Results indicated mostly satisfactory internal consistency for the subscales and high internal consistency for the total score of the scale. A factor analysis showed a one-factor solution that accounted for 50.21 % of the observed variance. Evidence for convergent validity, tested by evaluating the associations between borderline traits, anxiety, depression, stress, life satisfaction and impulsivity traits, was confirmed, but the assumptions for divergent validity were not met. Results are discussed considering previous studies. Future research is needed to fully evaluate its psychometric properties.
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- 2024
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7. Redox state alteration modulates astrocyte glucuronidation
- Author
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Heurtaux, T., Benani, A., Bianchi, A., Moindrot, A., Gradinaru, D., Magdalou, J., Netter, P., and Minn, A.
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- 2004
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8. Psychotropic effects of nicotine and cotinine in mice
- Author
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Vlasceanu, A.M., primary, Chirita, C., additional, Mihai, D.P., additional, Marineci, C.D., additional, Stan, M., additional, Gradinaru, D., additional, and Baconi, D.L., additional
- Published
- 2018
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9. Correlation between erythropoietin serum levels and erythrocyte susceptibility to lipid peroxidation in elderly with type 2 diabetes
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Gradinaru, D, primary, Margina, D, additional, Ilie, M, additional, Borsa, C, additional, Ionescu, C, additional, and Prada, GI, additional
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- 2015
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10. Semi-analytical computation of displacement in linear viscoelastic materials
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Spinu, S, primary and Gradinaru, D, additional
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- 2015
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11. An engineering model for yield inception in slip-stick elastic contacts
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Spinu, S, primary and Gradinaru, D, additional
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- 2015
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12. Effects induced by natural extracts on Daphnia magna exposed to UV toxicity
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Margina, D., primary, Olaru, O., additional, Gutu, C., additional, Florea, L., additional, Gradinaru, D., additional, Purdel, C., additional, and Ilie, M., additional
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- 2015
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13. The assessment of protein carbonyls in patients with type 2 diabetes
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Carmen, P., primary, Ines, D., additional, Denisa, M., additional, Gradinaru, D., additional, and Mihaela, I., additional
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- 2015
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14. Effects induced by polyphenol-rich natural extracts against lipoperoxidation – Protection against toxicant induced oxidative stress
- Author
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Margina, D., primary, Olaru, O., additional, Ilie, M., additional, Gutu, C., additional, Petrache, S., additional, Florea, L., additional, Gradinaru, D., additional, and Dinischiotu, A., additional
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- 2015
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15. In vitro studies regarding the effects of epigalocatechin gallate on biophysical properties of PBMC isolated from chronic hyperglycemia patients
- Author
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Margina, D., primary, Ilie, M., additional, Gradinaru, D., additional, Mitrea, N., additional, and Balalau, D., additional
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- 2011
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16. 410 THE EFFECT OF PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY UPON MMP2MMP9 TIMP1 AND NOX1 RELEASE IN PATIENTS WITH STABLE ANGINA
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Revnic, C., primary, Ginghina, C., additional, Mereuta, A., additional, Gradinaru, D., additional, and Revnic, F., additional
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- 2011
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17. 475 THE IMPACT OF PERCUTANEOUS CORONARY INTERVENTION (PCI) WITH STENT IMPLANTATION UPON MMP9 AND INFLAMATORY MARKERS IN PATIENTS WITH ACUTE CORONARY SYNDROMES
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Revnic, F., primary, Revnic, C.R., additional, Ginghina, C., additional, Mereuta, A., additional, Gradinaru, D., additional, Prada, G., additional, Prada, S., additional, Pena, C., additional, Borsa, C., additional, and Ionescu, C., additional
- Published
- 2011
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18. Correlations between eyelid tumors and tear lipocalin, lysozyme and lactoferrin concentrations in postmenopausal women.
- Author
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Careba, I., Gradinaru, D., Chiva, A., Totir, M., Ciuluvica, R., Gradinaru, S., and Ungureanu, E.
- Subjects
- *
LIPOCALIN-1 , *LYSOZYMES , *LACTOFERRIN , *POSTMENOPAUSE , *DISEASES in women ,EYELID tumors - Abstract
Rationale: Common ophthalmological problems are found in patients with eyelid tumors and include ocular surface diseases, such as dry eyes, eyelid disorders, excessive tearing and ocular inflammation. Objective: The potential correlation between the symptomatology, tear break-up time (TBUT) and lipocalin, lactoferrin and lysozyme concentrations in the tear film were investigated in a group of symptomatic dry-eyed postmenopausal (PM) women compared to agematched controls, considering the patients with eyelid tumors. Methods and Results: 66 females were divided into two groups of 33 females each, one group having dry eye (DE) and one asymptomatic group (non-dry eye) (NDE), based on their responses to the OSDI questionnaire, TBUT and Schirmer test evaluation. Tears were collected via capillary tubes. Tear lysozyme, lactoferrin and lipocalin concentrations were determined via electrophoresis and the results for patients with or without eyelid tumors were compared. The results revealed significant differences in lysozyme concentration between patients with or without eyelid tumors in the DE group (p = 0.004). Lower levels for TBUT and lactoferrin in the DE group were also found, compared to the NDE group for eyelid tumors patients. Tear lipocalins were in the same range in both groups. Discussion: Within a PM population, some components of the tear film were found to be at lower levels in patients with eyelid tumors, compared to patients without this pathology, which resulted in the development of DE or in the enhancement of the symptoms of an existing DE. [ABSTRACT FROM AUTHOR]
- Published
- 2015
19. Transition metal complexes with thiosemicarbazide-based ligands. 14. Iron(IV) complexes with 2,4-pentanedione bis(S-alkylisothiosemicarbazone). Crystal and molecular structure of iodo{2,4-pentanedione bis(S-ethylisothiosemicarbazonato)(3-)}iron(IV)
- Author
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Gerbeleu, N. V., primary, Simonov, Yu. A., additional, Arion, V. B., additional, Leovac, V. M., additional, Turta, K. I., additional, Indrichan, K. M., additional, Gradinaru, D. I., additional, Zavodnik, V. E., additional, and Malinovskii, T. I., additional
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- 1992
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20. High voltage high frequency silicon bipolar transistors.
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Gradinaru, D., Ng, W.T., and Salama, C.A.T.
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- 1999
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21. Rat olfactory bulb and epithelium UDP-glucuronosyltransferase 2A1 (UGT2A1) expression: in situ mRNA localization and quantitative analysis
- Author
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Heydel, J. M., Leclerc, S., Bernard, P., Pelczar, H., Gradinaru, D., Magdalou, J., Minn, A., Artur, Y., and Goudonnet, H.
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- 2001
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22. A COMPARATIVE STUDY OF THE EVOLUTION OF REAL INCOMES OF PENSIONERS AND UNEMPLOYED USING GENETIC ALGORITHMS
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Gradinaru Dorin and Balan Ionut
- Subjects
genetic algorithm, cross-over, mutation, unemployed, pensioners ,Business ,HF5001-6182 ,Finance ,HG1-9999 - Abstract
In a market economy we can have difficulties in real income measuring, due to changes in prices and wages that may be in short intervals of time. When we want to compare real income obtained in different periods of time it is used, most often, a "trash da
- Published
- 2009
23. In vitro studies regarding the protective effects of procaine and GH3 against lipid peroxidation
- Author
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Ungurianu, A., Denisa Margina, and Gradinaru, D.
24. A NUMERICAL SOLUTION TO THE CATTANEO-MINDLIN PROBLEM PART II: PROGRAM VALIDATION AND LOADING HISTORY SIMULATION
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Spinu Sergiu and Gradinaru Dorin
- Subjects
Technology ,Mechanical engineering and machinery ,TJ1-1570 - Published
- 2011
25. NUMERICAL ANALYSIS OF ELASTIC CONTACT BETWEEN FOURTH ORDER POLYNOMIAL SURFACES
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Gradinaru Dorin and Spinu Sergiu
- Subjects
Technology ,Mechanical engineering and machinery ,TJ1-1570 - Published
- 2011
26. NUMERICAL SIMULATION OF ELASTIC TORSIONAL CONTACT WITH SLIP AND STICK
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Gradinaru Dorin and Spinu Sergiu
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Technology ,Mechanical engineering and machinery ,TJ1-1570 - Published
- 2011
27. A NUMERICAL SOLUTION TO THE CATTANEO-MINDLIN PROBLEM PART I: ALGORITHM DESCRIPTION
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Spinu Sergiu and Gradinaru Dorin
- Subjects
Technology ,Mechanical engineering and machinery ,TJ1-1570 - Published
- 2011
28. Circulating cell-free DNA in health and disease - the relationship to health behaviours, ageing phenotypes and metabolomics
- Author
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Laura Kananen, Mikko Hurme, Alexander Bürkle, Maria Moreno-Villanueva, Jürgen Bernhardt, Florence Debacq-Chainiaux, Beatrix Grubeck-Loebenstein, Marco Malavolta, Andrea Basso, Francesco Piacenza, Sebastiano Collino, Efstathios S. Gonos, Ewa Sikora, Daniela Gradinaru, Eugene H. J. M. Jansen, Martijn E. T. Dollé, Michel Salmon, Wolfgang Stuetz, Daniela Weber, Tilman Grune, Nicolle Breusing, Andreas Simm, Miriam Capri, Claudio Franceschi, Eline Slagboom, Duncan Talbot, Claude Libert, Jani Raitanen, Seppo Koskinen, Tommi Härkänen, Sari Stenholm, Mika Ala-Korpela, Terho Lehtimäki, Olli T. Raitakari, Olavi Ukkola, Mika Kähönen, Marja Jylhä, Juulia Jylhävä, Tampere University, Health Sciences, BioMediTech, Department of Clinical Chemistry, Clinical Medicine, Department of Clinical Physiology and Nuclear Medicine, Kananen L., Hurme M., Burkle A., Moreno-Villanueva M., Bernhardt J., Debacq-Chainiaux F., Grubeck-Loebenstein B., Malavolta M., Basso A., Piacenza F., Collino S., Gonos E.S., Sikora E., Gradinaru D., Jansen E.H.J.M., Dolle M.E.T., Salmon M., Stuetz W., Weber D., Grune T., Breusing N., Simm A., Capri M., Franceschi C., Slagboom E., Talbot D., Libert C., Raitanen J., Koskinen S., Harkanen T., Stenholm S., Ala-Korpela M., Lehtimaki T., Raitakari O.T., Ukkola O., Kahonen M., Jylha M., and Jylhava J.
- Subjects
Aging ,Frailty ,Biology and Life Sciences ,Metabolomic ,3121 Internal medicine ,3142 Public health care science, environmental and occupational health ,3141 Health care science ,Cell-free DNA ,Health behaviours ,Medicine and Health Sciences ,Health behaviour ,Metabolomics ,3111 Biomedicine ,Geriatrics and Gerontology ,Morbidity ,Biomarker of ageing - Abstract
Circulating cell-free DNA (cf-DNA) has emerged as a promising biomarker of ageing, tissue damage and cellular stress. However, less is known about health behaviours, ageing phenotypes and metabolic processes that lead to elevated cf-DNA levels. We sought to analyse the relationship of circulating cf-DNA level to age, sex, smoking, physical activity, vegetable consumption, ageing phenotypes (physical functioning, the number of diseases, frailty) and an extensive panel of biomarkers including blood and urine metabolites and inflammatory markers in three human cohorts (N = 5385; 17–82 years). The relationships were assessed using correlation statistics, and linear and penalised regressions (the Lasso), also stratified by sex.cf-DNA levels were significantly higher in men than in women, and especially in middle-aged men and women who smoke, and in older more frail individuals. Correlation statistics of biomarker data showed that cf-DNA level was higher with elevated inflammation (C-reactive protein, interleukin-6), and higher levels of homocysteine, and proportion of red blood cells and lower levels of ascorbic acid. Inflammation (C-reactive protein, glycoprotein acetylation), amino acids (isoleucine, leucine, tyrosine), and ketogenesis (3-hydroxybutyrate) were included in the cf-DNA level-related biomarker profiles in at least two of the cohorts.In conclusion, circulating cf-DNA level is different by sex, and related to health behaviour, health decline and metabolic processes common in health and disease. These results can inform future studies where epidemiological and biological pathways of cf-DNA are to be analysed in details, and for studies evaluating cf-DNA as a potential clinical marker.
- Published
- 2023
- Full Text
- View/download PDF
29. Bacterial DNAemia in older participants and nonagenarian offspring and association with redox biomarkers
- Author
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Robertina Giacconi, Patrizia D’Aquila, Marco Malavolta, Francesco Piacenza, Alexander Bürkle, María Moreno Villanueva, Martijn E T Dollé, Eugène Jansen, Tilman Grune, Efstathios S Gonos, Claudio Franceschi, Miriam Capri, Daniela Gradinaru, Beatrix Grubeck-Loebenstein, Ewa Sikora, Wolfgang Stuetz, Daniela Weber, Olivier Toussaint, Florence Debacq-Chainiaux, Antti Hervonen, Mikko Hurme, P Eline Slagboom, Christiane Schön, Jürgen Bernhardt, Nicolle Breusing, Talbot Duncan, Giuseppe Passarino, Dina Bellizzi, Mauro Provinciali, Tampere University, BioMediTech, Giacconi R., D'Aquila P., Malavolta M., Piacenza F., Burkle A., Villanueva M.M., Dolle M.E.T., Jansen E., Grune T., Gonos E.S., Franceschi C., Capri M., Gradinaru D., Grubeck-Loebenstein B., Sikora E., Stuetz W., Weber D., Toussaint O., Debacq-Chainiaux F., Hervonen A., Hurme M., Slagboom P.E., Schon C., Bernhardt J., Breusing N., Duncan T., Passarino G., Bellizzi D., and Provinciali M.
- Subjects
Inflammation ,Aging ,Blood bacterial DNA ,Longevity ,Dysbiosis ,3111 Biomedicine ,Geriatrics and Gerontology ,Dysbiosi - Abstract
Aging and age-related diseases have been linked to microbial dysbiosis with changes in blood bacterial DNA concentration. This condition may promote chronic low-grade inflammation, which can be further aggravated by antioxidant nutrient deficiency. Low plasma carotenoids are associated with an increased risk of inflammation and cellular damage and predict mortality. However, no evidence is yet available on the relationship between antioxidants and the blood bacterial DNA (BB-DNA). Therefore, this study aimed to compare BB-DNA from (a) GO (nonagenarian offspring), (b) age-matched controls (Randomly recruited Age-Stratified Individuals from the General population [RASIG]), and (c) spouses of GO (SGO) recruited in the MARK-AGE project, as well as to investigate the association between BB-DNA, behavior habits, Charlson Comorbidity Index (CCI), leucocyte subsets, and the circulating levels of some antioxidants and oxidative stress markers. BB-DNA was higher in RASIG than GO and SGO, whereas GO and SGO participants showed similar values. BB-DNA increased in smokers and males with CCI ≥ 2 compared with those with CCI ≤ 1 within RASIG. Moreover, BB-DNA was positively associated with lymphocyte, neutrophil, and monocyte counts, but not with self-reported dietary habits. Higher quartiles of BB-DNA were associated with low lutein and zeaxanthin and elevated malondialdehyde plasma concentrations in RASIG. BB-DNA was also positively correlated with nitric oxide levels. Herein, we provide evidence of a reduced BB-DNA in individuals from long-living families and their spouses, suggesting a decreased microbial dysbiosis and bacterial systemic translocation. BB-DNA was also associated with smoking, CCI, leukocyte subsets, and some redox biomarkers in older participants.
- Published
- 2022
30. Do low molecular weight antioxidants contribute to the Protection against oxidative damage? The interrelation between oxidative stress and low molecular weight antioxidants based on data from the MARK-AGE study
- Author
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Ron Kohen, Ilya Pinchuk, Nicolle Breusing, Daniela Gradinaru, Martijn E.T. Dollé, Efstathios S. Gonos, Mikko Hurme, Maria Moreno-Villanueva, Wolfgang Stuetz, Claudio Franceschi, Dov Lichtenberg, Eugène H.J.M. Jansen, Miriam Capri, Florence Debacq-Chainiaux, Tilman Grune, Christiane Schön, Daniela Weber, Beatrix Grubeck-Loebenstein, Ewa Sikora, Jürgen Bernhardt, Alexander Bürkle, and Pinchuk I, Kohen R, Stuetz W, Weber D, Franceschi C, Capri M, Hurme M, Grubeck-Loebenstein B, Schön C, Bernhardt J, Debacq-Chainiaux F, Dollé MET, Jansen EHJM, Gonos ES, Sikora E, Breusing N, Gradinaru D, Moreno-Villanueva M, Bürkle A, Grune T, Lichtenberg D.
- Subjects
Antioxidant ,medicine.medical_treatment ,Biophysics ,Oxidative stressFree radicalsAntioxidantsReactive oxygen species ,Free radicals ,Low molecular weight antioxidants ,Pharmacology ,medicine.disease_cause ,Biochemistry ,Antioxidants ,chemistry.chemical_compound ,medicine ,Humans ,Molecular Biology ,Carotenoid ,chemistry.chemical_classification ,Reactive oxygen species ,Malondialdehyde ,Ascorbic acid ,Molecular Weight ,Oxidative Stress ,Cross-Sectional Studies ,chemistry ,Biomarker (medicine) ,Oxidation-Reduction ,Oxidative stress ,Biomarkers - Abstract
A redox steady state is important in maintaining vital cellular functions and is therefore homeostatically controlled by a number of antioxidative agents, the most important of which are enzymes. Oxidative Stress (OS) is associated with (or/and caused by) excessive production of damaging reactive oxygen and/or nitrogen species (ROS, RNS), which play a role in many pathologies. Because OS is a risk factor for many diseases, much effort (and money) is devoted to early diagnosis and treatment of OS. The desired benefit of the “identify (OS) and treat (by low molecular weight antioxidants, LMWA)” approach is to enable selective treatment of patients under OS. The present work aims at gaining understanding of the benefit of the antioxidants based on interrelationship between the concentration of different OS biomarkers and LMWA. Both the concentrations of a variety of biomarkers and of LMWA were previously determined and some analyses have been published by the MARK-AGE team. For the sake of simplicity, we assume that the concentration of an OS biomarker is a linear function of the concentration of a LMWA (if the association is due to causal relationship). A negative slope of this dependence (and sign of the correlation coefficient) can be intuitively expected for an antioxidant, a positive slope indicates that the LMWA is pro-oxidative, whereas extrapolation of the OS biomarker to [LMWA] = 0 is an approximation of the concentration of the OS biomarker in the absence of the LMWA. Using this strategy, we studied the effects of 12 LMWA (including tocopherols, carotenoids and ascorbic acid) on the OS status, as observed with 8 biomarkers of oxidative damage (including malondialdehyde, protein carbonyls, 3-nitrotyrosine). The results of this communication show that in a cross-sectional study the LMWA contribute little to the redox state and that different “antioxidants” are very different, so that single LMWA treatment of OS is not scientifically justified assuming our simple model. In view of the difficulty of quantitating the OS and the very different effects of various LMWA, the use of the “identify and treat” approach is questionable.
- Published
- 2021
31. Development and validation of cardiometabolic risk predictive models based on LDL oxidation and candidate geromarkers from the MARK-AGE data.
- Author
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Valeanu A, Margina D, Weber D, Stuetz W, Moreno-Villanueva M, Dollé MET, Jansen EH, Gonos ES, Bernhardt J, Grubeck-Loebenstein B, Weinberger B, Fiegl S, Sikora E, Mosieniak G, Toussaint O, Debacq-Chainiaux F, Capri M, Garagnani P, Pirazzini C, Bacalini MG, Hervonen A, Slagboom PE, Talbot D, Breusing N, Frank J, Bürkle A, Franceschi C, Grune T, and Gradinaru D
- Subjects
- Humans, Middle Aged, Male, Female, Aged, Adult, Cross-Sectional Studies, Biomarkers blood, Biomarkers metabolism, Oxidation-Reduction, Risk Assessment methods, Cardiovascular Diseases metabolism, Cardiovascular Diseases blood, Aging metabolism, Obesity metabolism, Obesity blood, Risk Factors, Hypertension metabolism, Hypertension blood, Lipoproteins, LDL blood, Lipoproteins, LDL metabolism, Cardiometabolic Risk Factors, Machine Learning
- Abstract
The predictive value of the susceptibility to oxidation of LDL particles (LDLox) in cardiometabolic risk assessment is incompletely understood. The main objective of the current study was to assess its relationship with other relevant biomarkers and cardiometabolic risk factors from MARK-AGE data. A cross-sectional observational study was carried out on 1089 subjects (528 men and 561 women), aged 40-75 years old, randomly recruited age- and sex-stratified individuals from the general population. A correlation analysis exploring the relationships between LDLox and relevant biomarkers was undertaken, as well as the development and validation of several machine learning algorithms, for estimating the risk of the combined status of high blood pressure and obesity for the MARK-AGE subjects. The machine learning models yielded Area Under the Receiver Operating Characteristic Curve Score ranging 0.783-0.839 for the internal validation, while the external validation resulted in an Under the Receiver Operating Characteristic Curve Score between 0.648 and 0.787, with the variables based on LDLox reaching significant importance within the obtained predictions. The current study offers novel insights regarding the combined effects of LDL oxidation and other ageing markers on cardiometabolic risk. Future studies might be extended on larger patient cohorts, in order to obtain reproducible clinical assessment models., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
32. Relationships between Serum Biomarkers of Oxidative Stress and Tobacco Smoke Exposure in Patients with Mental Disorders.
- Author
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Vlasceanu AM, Gradinaru D, Stan M, Nitescu VG, and Baconi DL
- Abstract
The role of cigarette smoking as an aggravating factor of systemic oxidative stress in patients with mental disorders has not been extensively investigated, although significantly higher rates of smoking are recorded in these subjects in comparison with the general population. In the present study, we tested the hypothesis that smoking might be an exacerbator of systemic oxidative stress, being directly correlated with the degree of exposure to tobacco smoke. We analyzed, in 76 adult subjects from a public health care unit, the relationships between serum cotinine levels as a marker of tobacco smoke exposure, and three biomarkers of oxidative stress: the serum glutathione (GSH), the advanced oxidation protein products (AOPPs), and the total serum antioxidant status (FRAP). The results indicate that the degree of tobacco smoke exposure was inversely associated with GSH levels in both passive and active smokers, suggesting that smoke particulate components' toxicity is associated with a systemic GSH depletion. Paradoxically, the lowest AOPP levels which were positively associated with GSH, were recorded in active smoking patients whereas in passive smokers individual values of AOPPs decreased along with the increase in GSH levels. Our data suggest that an enhanced inhalation of particulate constituents of cigarette smoke could induce critical changes in systemic redox homeostasis and GSH can no longer exert its antioxidant role.
- Published
- 2023
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33. Bacterial DNAemia in Older Participants and Nonagenarian Offspring and Association With Redox Biomarkers: Results From MARK-AGE Study.
- Author
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Giacconi R, D'Aquila P, Malavolta M, Piacenza F, Bürkle A, Villanueva MM, Dollé MET, Jansen E, Grune T, Gonos ES, Franceschi C, Capri M, Gradinaru D, Grubeck-Loebenstein B, Sikora E, Stuetz W, Weber D, Toussaint O, Debacq-Chainiaux F, Hervonen A, Hurme M, Slagboom PE, Schön C, Bernhardt J, Breusing N, Duncan T, Passarino G, Bellizzi D, and Provinciali M
- Subjects
- Aged, Aged, 80 and over, Humans, Male, Antioxidants metabolism, Biomarkers, DNA, Bacterial, Inflammation, Oxidation-Reduction, Oxidative Stress, Dysbiosis, Nonagenarians
- Abstract
Aging and age-related diseases have been linked to microbial dysbiosis with changes in blood bacterial DNA concentration. This condition may promote chronic low-grade inflammation, which can be further aggravated by antioxidant nutrient deficiency. Low plasma carotenoids are associated with an increased risk of inflammation and cellular damage and predict mortality. However, no evidence is yet available on the relationship between antioxidants and the blood bacterial DNA (BB-DNA). Therefore, this study aimed to compare BB-DNA from (a) GO (nonagenarian offspring), (b) age-matched controls (Randomly recruited Age-Stratified Individuals from the General population [RASIG]), and (c) spouses of GO (SGO) recruited in the MARK-AGE project, as well as to investigate the association between BB-DNA, behavior habits, Charlson Comorbidity Index (CCI), leucocyte subsets, and the circulating levels of some antioxidants and oxidative stress markers. BB-DNA was higher in RASIG than GO and SGO, whereas GO and SGO participants showed similar values. BB-DNA increased in smokers and males with CCI ≥ 2 compared with those with CCI ≤ 1 within RASIG. Moreover, BB-DNA was positively associated with lymphocyte, neutrophil, and monocyte counts, but not with self-reported dietary habits. Higher quartiles of BB-DNA were associated with low lutein and zeaxanthin and elevated malondialdehyde plasma concentrations in RASIG. BB-DNA was also positively correlated with nitric oxide levels. Herein, we provide evidence of a reduced BB-DNA in individuals from long-living families and their spouses, suggesting a decreased microbial dysbiosis and bacterial systemic translocation. BB-DNA was also associated with smoking, CCI, leukocyte subsets, and some redox biomarkers in older participants., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America.)
- Published
- 2023
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34. Discovery of New Microbial Collagenase Inhibitors.
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Nitulescu G, Mihai DP, Zanfirescu A, Stan MS, Gradinaru D, and Nitulescu GM
- Abstract
Bacterial virulence factors are mediating bacterial pathogenesis and infectivity. Collagenases are virulence factors secreted by several bacterial stains, such as Clostridium , Bacillus , Vibrio and Pseudomonas . These enzymes are among the most efficient degraders of collagen, playing a crucial role in host colonization. Thus, they are an important target for developing new anti-infective agents because of their pivotal roles in the infection process. A primary screening using a fluorescence resonance energy-transfer assay was used to experimentally evaluate the inhibitory activity of 77 compounds on collagenase A. Based on their inhibitory activity and chemical diversity, a small number of compounds was selected to determine the corresponding half maximal inhibitory con-centration (IC50). Additionally, we used molecular docking to get a better understanding of the enzyme-compound interaction. Several natural compounds (capsaicin, 4',5-dihydroxyflavone, curcumin, dihydrorobinetin, palmatine chloride, biochanin A, 2'-hydroxychalcone, and juglone) were identified as promising candidates for further development into useful anti-infective agents against infections caused by multi-drug-resistant bacterial pathogens which include collagenase A in their enzymatic set.
- Published
- 2022
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35. Candidates for Repurposing as Anti-Virulence Agents Based on the Structural Profile Analysis of Microbial Collagenase Inhibitors.
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Nitulescu G, Nitulescu GM, Zanfirescu A, Mihai DP, and Gradinaru D
- Abstract
The pharmacological inhibition of the bacterial collagenases (BC) enzymes is considered a promising strategy to block the virulence of the bacteria without targeting the selection mechanism leading to drug resistance. The chemical structures of the Clostridium perfringens collagenase A (ColA) inhibitors were analyzed using Bemis-Murcko skeletons, Murcko frameworks, the type of plain rings, and docking studies. The inhibitors were classified based on their structural architecture and various scoring methods were implemented to predict the probability of new compounds to inhibit ColA and other BC. The analyses indicated that all compounds contain at least one aromatic ring, which is often a nitrobenzene fragment. 2-Nitrobenzene based compounds are, on average, more potent BC inhibitors compared to those derived from 4-nitrobenzene. The molecular descriptors MDEO-11, AATS0s, ASP-0, and MAXDN were determined as filters to identify new BC inhibitors and highlighted the necessity for a compound to contain at least three primary oxygen atoms. The DrugBank database was virtually screened using the developed methods. A total of 100 compounds were identified as potential BC inhibitors, of which, 10 are human approved drugs. Benzthiazide, entacapone, and lodoxamide were chosen as the best candidates for in vitro testing based on their pharmaco-toxicological profile.
- Published
- 2021
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36. Do low molecular weight antioxidants contribute to the Protection against oxidative damage? The interrelation between oxidative stress and low molecular weight antioxidants based on data from the MARK-AGE study.
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Pinchuk I, Kohen R, Stuetz W, Weber D, Franceschi C, Capri M, Hurme M, Grubeck-Loebenstein B, Schön C, Bernhardt J, Debacq-Chainiaux F, Dollé MET, Jansen EHJM, Gonos ES, Sikora E, Breusing N, Gradinaru D, Moreno-Villanueva M, Bürkle A, Grune T, and Lichtenberg D
- Subjects
- Antioxidants chemistry, Cross-Sectional Studies, Humans, Molecular Weight, Oxidation-Reduction, Antioxidants pharmacology, Biomarkers metabolism, Oxidative Stress drug effects
- Abstract
A redox steady state is important in maintaining vital cellular functions and is therefore homeostatically controlled by a number of antioxidative agents, the most important of which are enzymes. Oxidative Stress (OS) is associated with (or/and caused by) excessive production of damaging reactive oxygen and/or nitrogen species (ROS, RNS), which play a role in many pathologies. Because OS is a risk factor for many diseases, much effort (and money) is devoted to early diagnosis and treatment of OS. The desired benefit of the "identify (OS) and treat (by low molecular weight antioxidants, LMWA)" approach is to enable selective treatment of patients under OS. The present work aims at gaining understanding of the benefit of the antioxidants based on interrelationship between the concentration of different OS biomarkers and LMWA. Both the concentrations of a variety of biomarkers and of LMWA were previously determined and some analyses have been published by the MARK-AGE team. For the sake of simplicity, we assume that the concentration of an OS biomarker is a linear function of the concentration of a LMWA (if the association is due to causal relationship). A negative slope of this dependence (and sign of the correlation coefficient) can be intuitively expected for an antioxidant, a positive slope indicates that the LMWA is pro-oxidative, whereas extrapolation of the OS biomarker to [LMWA] = 0 is an approximation of the concentration of the OS biomarker in the absence of the LMWA. Using this strategy, we studied the effects of 12 LMWA (including tocopherols, carotenoids and ascorbic acid) on the OS status, as observed with 8 biomarkers of oxidative damage (including malondialdehyde, protein carbonyls, 3-nitrotyrosine). The results of this communication show that in a cross-sectional study the LMWA contribute little to the redox state and that different "antioxidants" are very different, so that single LMWA treatment of OS is not scientifically justified assuming our simple model. In view of the difficulty of quantitating the OS and the very different effects of various LMWA, the use of the "identify and treat" approach is questionable., (Copyright © 2021. Published by Elsevier Inc.)
- Published
- 2021
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37. Procaine-The Controversial Geroprotector Candidate: New Insights Regarding Its Molecular and Cellular Effects.
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Gradinaru D, Ungurianu A, Margina D, Moreno-Villanueva M, and Bürkle A
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- Anesthetics, Local adverse effects, Animals, Antioxidants adverse effects, Epigenesis, Genetic drug effects, Humans, Procaine adverse effects, Aging drug effects, Anesthetics, Local pharmacology, Antioxidants pharmacology, Procaine pharmacology
- Abstract
Since its discovery in 1905 and its employment in everyday medical practice as a local anesthetic, to its highly controversial endorsement as an "anti-aging" molecule in the sixties and seventies, procaine is part of the history of medicine and gerontoprophylaxis. Procaine can be considered a "veteran" drug due to its long-time use in clinical practice, but is also a molecule which continues to incite interest, revealing new biological and pharmacological effects within novel experimental approaches. Therefore, this review is aimed at exploring and systematizing recent data on the biochemical, cellular, and molecular mechanisms involved in the antioxidant and potential geroprotective effects of procaine, focusing on the following aspects: (1) the research state-of-the-art, through an objective examination of scientific literature within the last 30 years, describing the positive, as well as the negative reports; (2) the experimental data supporting the beneficial effects of procaine in preventing or alleviating age-related pathology; and (3) the multifactorial pathways procaine impacts oxidative stress, inflammation, atherogenesis, cerebral age-related pathology, DNA damage, and methylation. According to reviewed data, procaine displayed antioxidant and cytoprotective actions in experimental models of myocardial ischemia/reperfusion injury, lipoprotein oxidation, endothelial-dependent vasorelaxation, inflammation, sepsis, intoxication, ionizing irradiation, cancer, and neurodegeneration. This analysis painted a complex pharmacological profile of procaine: a molecule that has not yet fully expressed its therapeutic potential in the treatment and prevention of aging-associated diseases. The numerous recent reports found demonstrate the rising interest in researching the multiple actions of procaine regulating key processes involved in cellular senescence. Its beneficial effects on cell/tissue functions and metabolism could designate procaine as a valuable candidate for the well-established Geroprotectors database., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 Daniela Gradinaru et al.)
- Published
- 2021
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38. The Radioprotective Effect of Procaine and Procaine-Derived Product Gerovital H3 in Lymphocytes from Young and Aged Individuals.
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Ungurianu A, Margina D, Borsa C, Ionescu C, von Scheven G, Oziol L, Faure P, Artur Y, Bürkle A, Gradinaru D, and Moreno-Villanueva M
- Subjects
- Adult, Aged, Humans, Procaine pharmacology, Lymphocytes radiation effects, Procaine therapeutic use, Radiation, Ionizing
- Abstract
Ionizing radiation induces genomic instability in living organisms, and several studies reported an ageing-dependent radiosensitivity. Chemical compounds, such as scavengers, radioprotectors, and modifiers, contribute to reducing the radiation-associated toxicity. These compounds are often antioxidants, and therefore, in order to be effective, they must be present before or during exposure to radiation. However, not all antioxidants provide radioprotection. In this study, we investigated the effects of procaine and of a procaine-based product Gerovital H3 (GH3) on the formation of endogenous and X-ray-induced DNA strand breaks in peripheral blood mononuclear cells (PBMCs) isolated from young and elderly individuals. Interestingly, GH3 showed the strongest radioprotective effects in PBMCs from young subjects, while procaine reduced the endogenous amount of DNA strand breaks more pronounced in aged individuals. Both procaine and GH3 inhibited lipid peroxidation, but procaine was more effective in inhibiting mitochondria free radicals' generation, while GH3 showed a higher antioxidant action on macrophage-induced low-density lipoprotein oxidation. Our findings provide new insights into the mechanisms underlying the distinct effects of procaine and GH3 on DNA damage., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 Anca Ungurianu et al.)
- Published
- 2020
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39. Gender- and age-dependencies of oxidative stress, as detected based on the steady state concentrations of different biomarkers in the MARK-AGE study.
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Pinchuk I, Weber D, Kochlik B, Stuetz W, Toussaint O, Debacq-Chainiaux F, Dollé MET, Jansen EHJM, Gonos ES, Sikora E, Breusing N, Gradinaru D, Sindlinger T, Moreno-Villanueva M, Bürkle A, Grune T, and Lichtenberg D
- Subjects
- Adult, Age Factors, Aged, Cross-Sectional Studies, Energy Metabolism, Female, Health Status Indicators, Humans, Male, Middle Aged, Oxidation-Reduction, Public Health Surveillance, Sex Factors, Biomarkers blood, Oxidative Stress
- Abstract
Recently, Weber et al. published a thorough investigation of the age-dependency of oxidative stress (OS) determined by the steady state concentrations of different compounds - oxidation products and antioxidants - that are in common use as biomarkers of OS in 2207 healthy individuals of the cross-sectional MARK-AGE Project. The correlations among biomarkers were significant but weak. These findings may indicate different manifestations of OS and must further be evaluated. Here, we report a refined analysis of OS based on the above-mentioned original data. We show that malondialdehyde (MDA) appears to be sensitive to both gender and age. It is significantly lower and shows a greater age-dependence in women than in men. The age-dependency of MDA in women arises in a stepwise fashion. The age-dependent slope of the steady state concentration is maximal at the age between 50 and 55 years, indicating that it may be attributed to the change of metabolism in the post-menopause. Interestingly, total glutathione (GSH) decreased with age simultaneously with the increase in MDA. Different biomarkers yield different gender- and age-dependencies. Unlike the concentration of MDA, the concentrations of the other two oxidation products, i.e. protein carbonyls and 3-nitrotyrosine were similar in men and women and appeared to be independent of age in the healthy study population. The analyzed antioxidants exhibited different gender- and age-dependencies. In conclusion, it appears that all the biomarkers assessed here reflect different types of OS and that MDA and GSH reflect the same type of OS., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2019
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40. Insulin-Leptin Axis, Cardiometabolic Risk and Oxidative Stress in Elderly with Metabolic Syndrome.
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Gradinaru D, Khaddour H, Margina D, Ungurianu A, Borsa C, Ionescu C, Prada GI, Usher J, and Elshimali Y
- Abstract
Insulin and leptin have an overlapping anorexigenic action as well as opposite effects on glucose and lipid metabolism. The study focuses on the biochemical and clinical relevance of new indices of insulin-leptin axis utilized in the study of the relationships between leptinemia, insulin sensitivity and oxidative stress, in elderly subjects with metabolic syndrome. We conducted clinical studies on elderly people with metabolic syndrome versus control subjects by creating new insulin-adipogenic indices, namely Insulin-to-Leptin Ratio (ILR) and Insulin-Adipogenic Resistance index (IAR-index). Inflammation and oxidative stress biomarkers evaluated were the high-sensitivity C-reactive protein (hsCRP), the advanced oxidation protein products (AOPP), and the serum antioxidant capacity measured as ferric reducing antioxidant potential (FRAP). The metabolic syndrome group showed significantly (p<0.01) lower levels of ILR and not significant (p=0.09) higher values of IAR-index, as compared to the control group. In metabolic syndrome subjects, the IAR-index was significantly positively correlated with uric acid (r=0.313, p<0.05), FRAP (r=0.347, p<0.05) and AOPP (r=0.677, p<0.01), and negatively correlated with HDL-cholesterol (r=- 0.340, p<0.05) as well as with the ratio FRAP/uric acid (r=- 0.315, p<0.05). ILR and IAR-index reflected the biological state of adipose and pancreatic β-cells and seem to depict the adipo-insular axis status related to metabolic and oxidative stress better than individual markers. Therefore, ILR and IAR-index could represent integrated high-potential biomarkers for disease and patient stratification., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)
- Published
- 2018
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41. Optimization Of Cancer Treatment Through Overcoming Drug Resistance.
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Elshimali YI, Wu Y, Khaddour H, Wu Y, Gradinaru D, Sukhija H, Chung SS, and Vadgama JV
- Abstract
Cancer Drug resistance is a medical concern that requires extensive research and a thorough understanding in order to overcome. Remarkable achievements related to this field have been accomplished and further work is needed in order to optimize the cure for cancer and serve as the basis for precise medicine with few or no side effects.
- Published
- 2018
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42. Chronic Monosodium Glutamate Administration Induced Hyperalgesia in Mice.
- Author
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Zanfirescu A, Cristea AN, Nitulescu GM, Velescu BS, and Gradinaru D
- Subjects
- Animals, Behavior, Animal drug effects, Brain drug effects, Brain metabolism, Brain physiopathology, Disease Models, Animal, Dose-Response Relationship, Drug, Drug Administration Schedule, Flavoring Agents administration & dosage, Formaldehyde, Hot Temperature, Hyperalgesia metabolism, Hyperalgesia physiopathology, Hyperalgesia psychology, Male, Mice, Nitric Oxide metabolism, Nitric Oxide Synthase metabolism, Nociceptive Pain metabolism, Nociceptive Pain physiopathology, Nociceptive Pain psychology, Reaction Time drug effects, Sodium Glutamate administration & dosage, Time Factors, Flavoring Agents toxicity, Hyperalgesia chemically induced, Nociceptive Pain chemically induced, Pain Threshold drug effects, Sodium Glutamate toxicity
- Abstract
Monosodium glutamate (MSG) is a widely used food additive. Although it is generally considered safe, some questions regarding the impact of its use on general health have arisen. Several reports correlate MSG consumption with a series of unwanted reactions, including headaches and mechanical sensitivity in pericranial muscles. Endogenous glutamate plays a significant role in nociceptive processing, this neurotransmitter being associated with hyperalgesia and central sensitization. One of the mechanisms underlying these phenomena is the stimulation of Ca
2+ /calmodulin sensitive nitric oxide synthase, and a subsequent increase in nitric oxide production. This molecule is a key player in nociceptive processing, with implications in acute and chronic pain states. Our purpose was to investigate the effect of this food additive on the nociceptive threshold when given orally to mice. Hot-plate and formalin tests were used to assess nociceptive behaviour. We also tried to determine if a correlation between chronic administration of MSG and variations in central nitric oxide (NO) concentration could be established. We found that a dose of 300 mg/kg MSG given for 21 days reduces the pain threshold and is associated with a significant increase in brain NO level. The implications of these findings on food additive-drug interaction, and on pain perception in healthy humans, as well as in those suffering from affections involving chronic pain, are still to be investigated., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.- Published
- 2017
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43. Adiponectin: possible link between metabolic stress and oxidative stress in the elderly.
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Gradinaru D, Margina D, Borsa C, Ionescu C, Ilie M, Costache M, Dinischiotu A, and Prada GI
- Subjects
- Adiponectin metabolism, Aged, Biomarkers blood, Case-Control Studies, Cholesterol, HDL blood, Female, Humans, Insulin Resistance, Lipoproteins, LDL blood, Male, Metabolic Syndrome etiology, Oxidation-Reduction, Risk Factors, Uric Acid blood, Adiponectin blood, Aging metabolism, Metabolic Syndrome blood, Oxidative Stress
- Abstract
Objective: The aim of this study was to evaluate the relationships between the serum levels of adiponectin and systemic oxidative stress exerted on lipids, proteins, as well as endothelial function and cardiovascular diseases (CVD) risk markers, in elderly subjects with metabolic syndrome (MS)., Methods: The serum advanced glycation and oxidation protein products, low-density lipoprotein susceptibility to oxidation (oxLDL), nitric oxide metabolic pathway products (NOx), serum lipid peroxidation, as well as total antioxidant/oxidative capacity (TAC/TOC), were analyzed in elderly subjects with MS (n = 44), compared to aged-matched control (n = 39)., Results: We pointed out significantly lower levels of adiponectin in elderly MS subjects concomitantly with significantly higher levels of oxidative stress and CVD risk markers. Significant positive correlations were found between serum adiponectin levels and HDL-cholesterol (p < 0.05) and the total cholesterol/LDL-cholesterol ratio (p < 0.01). Additionally, adiponectin levels were significantly inversely associated with insulin resistance index (HOMA-IR, r = -0.348; p < 0.05) and serum lipid peroxidation (r = -0.337; p < 0.05), and significantly positively with the antioxidant capacity (TAC, r = 0.339; p < 0.05). Conversely, adiponectin levels were significantly negatively (r = -0.310; p < 0.05) associated with serum uric acid concentration., Conclusions: The major protective role of adiponectin versus stress related to an impaired glucose and lipid metabolism suggests that adiponectin plays a critical role in adiposity-related metabolic stress and redox homeostasis.
- Published
- 2017
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44. MARK-AGE biomarkers of ageing.
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Bürkle A, Moreno-Villanueva M, Bernhard J, Blasco M, Zondag G, Hoeijmakers JH, Toussaint O, Grubeck-Loebenstein B, Mocchegiani E, Collino S, Gonos ES, Sikora E, Gradinaru D, Dollé M, Salmon M, Kristensen P, Griffiths HR, Libert C, Grune T, Breusing N, Simm A, Franceschi C, Capri M, Talbot D, Caiafa P, Friguet B, Slagboom PE, Hervonen A, Hurme M, and Aspinall R
- Subjects
- European Union, Female, Humans, Male, Aging metabolism, Biomarkers metabolism
- Abstract
Many candidate biomarkers of human ageing have been proposed in the scientific literature but in all cases their variability in cross-sectional studies is considerable, and therefore no single measurement has proven to serve a useful marker to determine, on its own, biological age. A plausible reason for this is the intrinsic multi-causal and multi-system nature of the ageing process. The recently completed MARK-AGE study was a large-scale integrated project supported by the European Commission. The major aim of this project was to conduct a population study comprising about 3200 subjects in order to identify a set of biomarkers of ageing which, as a combination of parameters with appropriate weighting, would measure biological age better than any marker in isolation., (Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)
- Published
- 2015
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45. Oxidized LDL and NO synthesis--Biomarkers of endothelial dysfunction and ageing.
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Gradinaru D, Borsa C, Ionescu C, and Prada GI
- Subjects
- Biomarkers blood, Humans, Aging blood, Cardiovascular Diseases blood, Endothelium, Vascular metabolism, Lipoproteins, LDL blood, Nitric Oxide blood, Oxidative Stress
- Abstract
Oxidized LDL (oxLDL) and nitric oxide (NO) exert contradictory actions within the vascular endothelium microenvironment influencing key events in atherogenesis. OxLDL and NO are so far regarded as representative parameters of oxidative stress and endothelial dysfunction, new targets in prevention, diagnosis and therapy of cardiovascular diseases, and also as candidate biomarkers in evaluating the human biological age. The aim of this review is to explore recent literature on molecular mechanisms and pathophysiological relationships between LDL oxidation, NO synthesis and vascular endothelium function/dysfunction in ageing, focusing on the following aspects: (1) the impact of metabolic status on both LDL oxidation and NO synthesis in relation with oxidative stress, (2) the use of oxidized LDL and NO activity as biomarkers in human studies reporting on cardiovascular outcomes, and (3) evidences supporting the importance of oxidized LDL and NO activity as relevant biomarkers in vascular ageing and age-related diseases., (Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)
- Published
- 2015
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46. Validation of protein carbonyl measurement: a multi-centre study.
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Augustyniak E, Adam A, Wojdyla K, Rogowska-Wrzesinska A, Willetts R, Korkmaz A, Atalay M, Weber D, Grune T, Borsa C, Gradinaru D, Chand Bollineni R, Fedorova M, and Griffiths HR
- Subjects
- Animals, Biotin analogs & derivatives, Biotin metabolism, Liver metabolism, Mass Spectrometry, Rats, Ultraviolet Rays, Oxidation-Reduction radiation effects, Protein Carbonylation radiation effects, Proteins metabolism
- Abstract
Protein carbonyls are widely analysed as a measure of protein oxidation. Several different methods exist for their determination. A previous study had described orders of magnitude variance that existed when protein carbonyls were analysed in a single laboratory by ELISA using different commercial kits. We have further explored the potential causes of variance in carbonyl analysis in a ring study. A soluble protein fraction was prepared from rat liver and exposed to 0, 5 and 15min of UV irradiation. Lyophilised preparations were distributed to six different laboratories that routinely undertook protein carbonyl analysis across Europe. ELISA and Western blotting techniques detected an increase in protein carbonyl formation between 0 and 5min of UV irradiation irrespective of method used. After irradiation for 15min, less oxidation was detected by half of the laboratories than after 5min irradiation. Three of the four ELISA carbonyl results fell within 95% confidence intervals. Likely errors in calculating absolute carbonyl values may be attributed to differences in standardisation. Out of up to 88 proteins identified as containing carbonyl groups after tryptic cleavage of irradiated and control liver proteins, only seven were common in all three liver preparations. Lysine and arginine residues modified by carbonyls are likely to be resistant to tryptic proteolysis. Use of a cocktail of proteases may increase the recovery of oxidised peptides. In conclusion, standardisation is critical for carbonyl analysis and heavily oxidised proteins may not be effectively analysed by any existing technique., (Copyright © 2015. Published by Elsevier B.V.)
- Published
- 2015
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47. In vitro effects of prolonged exposure to quercetin and epigallocatechin gallate of the peripheral blood mononuclear cell membrane.
- Author
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Margina D, Ilie M, Manda G, Neagoe I, Danciulescu-Miulescu R, Purdel CN, and Gradinaru D
- Subjects
- Case-Control Studies, Catechin pharmacology, Cell Membrane drug effects, Cells, Cultured, Drug Evaluation, Preclinical, Fluorescence Polarization, Glycation End Products, Advanced blood, Hypercholesterolemia blood, Membrane Fluidity drug effects, Membrane Potentials drug effects, Oxidative Stress, Antioxidants pharmacology, Catechin analogs & derivatives, Cell Membrane metabolism, Leukocytes, Mononuclear drug effects, Quercetin pharmacology
- Abstract
The study aimed to assess biophysical changes that take place in the peripheral blood mononuclear cell (PBMC) membranes when exposed in vitro to 10 μM quercetin or epigallocatechin gallate (EGCG) for 24 and 48 h. PBMCs isolated from hypercholesterolemia patients were compared to those from normocholesterolemia subjects. The membrane fluidity and transmembrane potential were evaluated and the results were correlated with biochemical parameters relevant to oxidative stress, assessed in the patients' plasma. The baseline value of PBMC membrane anisotropy for the hypercholesterolemia patients was lower than that of the control group. These results correlated with the plasma levels of advanced glycation end products, which were significantly higher in the hypercholesterolemia group, and the total plasma antioxidant status, which was significantly higher in normocholesterolemia subjects. In the case of normocholesterolemia cells in vitro, polyphenols induced a decrease in membrane anisotropy (7.25-11.88% at 24 h, 1.82-2.26% at 48 h) and a hyperpolarizing effect (8.30-8.90% at 24 h and 4.58-13.00% at 48 h). The same effect was induced in hypercholesterolemia cells, but only after 48 h exposure to the polyphenols: the decrease in membrane anisotropy was 5.70% for quercetin and 2.33% for EGCG. After 48 h of in vitro incubation with the polyphenols, PBMCs isolated from hypercholesterolemia patients exhibited the effects that had been registered in cells from normocholesterolemia subjects after 24 h exposure. These results outlined the beneficial action of the studied polyphenols, quercetin and EGCG, as dietary supplements in normocholesterolemia and hypercholesterolemia patients.
- Published
- 2014
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48. Membranar effects exerted in vitro by polyphenols - quercetin, epigallocatechin gallate and curcumin - on HUVEC and Jurkat cells, relevant for diabetes mellitus.
- Author
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Margina D, Gradinaru D, Manda G, Neagoe I, and Ilie M
- Subjects
- Anisotropy, Antioxidants pharmacology, Catechin pharmacology, Cell Membrane metabolism, Cell Survival drug effects, Chemokine CCL2 metabolism, Diabetes Mellitus drug therapy, Diabetes Mellitus metabolism, Human Umbilical Vein Endothelial Cells drug effects, Humans, Jurkat Cells drug effects, Lipid Peroxidation drug effects, Membrane Potentials drug effects, Catechin analogs & derivatives, Cell Membrane drug effects, Curcumin pharmacology, Quercetin pharmacology
- Abstract
Polyphenols are largely studied for their beneficial action in various pathologies, but the correlation with their effects on cell membranes is still elusive. In the present study we assessed the effects exerted in vitro by quercetin, epigallocatechin gallate and curcumin on membrane fluidity and transmembrane potential of human umbilical vein endothelial cells and Jurkat T lymphoblasts, in experimental conditions mimicking diabetes mellitus, i.e. high glucose conditions or increased concentration of advanced glycation end products. Results showed that the investigated polyphenols had beneficial effects on cell membranes altered in diabetic conditions, by restoring transmembrane potential and by membrane "stiffening". Moreover, they limited the release of pro-inflammatory factors, like monocyte chemotactic protein-1. These effects were more obvious for cells exposed to advanced glycation end products specific for the late stages of diabetes. Apparently, the inhibitory action of polyphenols on lipid peroxidation was associated with a decrease of membrane fluidity. Concluding, our in vitro study highlighted the potential beneficial action of polyphenols mainly in the late stages of diabetes, exerted at the level of membrane fluidity and transmembrane potential, accompanied by an anti-inflammatory effect on endothelial and immune cells., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2013
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49. Advanced oxidative and glycoxidative protein damage markers in the elderly with type 2 diabetes.
- Author
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Gradinaru D, Borsa C, Ionescu C, and Margina D
- Subjects
- Aged, Aging pathology, Atherosclerosis blood, Biomarkers blood, Diabetes Mellitus, Type 2 pathology, Female, Humans, Insulin Resistance, Male, Middle Aged, Nitric Oxide blood, Aging blood, Diabetes Mellitus, Type 2 blood, Glycation End Products, Advanced blood, Lipoproteins, LDL blood, Oxidative Stress
- Abstract
We aimed to explore the association of advanced oxidation and advanced glycation of proteins, and their interrelations with endothelial nitric oxide synthesis, oxidative stress, metabolic profile as well as other atherosclerotic risk markers in prediabetic and diabetic elderly subjects. Advanced glycation end products (AGEs), advanced oxidation protein products (AOPPs), low-density lipoprotein susceptibility to oxidation (oxLDL) and nitric oxide metabolic pathway products (NOx) were assessed in subjects with impaired fasting glucose (prediabetes, IFG; n=90), and type 2 diabetes mellitus (T2DM, n=95) versus control subjects (n=88). Higher levels of AOPPs, AGEs, oxLDL, NOx, atherosclerosis risk markers, and insulin resistance were pointed out in IFG and T2DM groups compared with control. Strong positive associations (p<0.01) of AGEs with fasting glucose and HbA1c were found in both hyperglycemic groups, whereas AOPPs were significantly correlated (p<0.01) only in T2DM. In T2DM, AGEs and AOPPs significantly (p<0.01) correlated with insulin resistance index HOMA-IR, oxLDL and small LDL particle size (TG/HDL-C), and positively with NOx. Direct associations of AGEs and AOPPs with TC/HDL-C and oxLDL/HDL-C, and AGEs-AOPPs interrelations (p<0.01) were identified in IFG and T2DM groups. AGEs and AOPPs in combination with oxLDL and NOx could be important biomarkers for evaluating the association between diabetes and atherosclerotic disorders in aging diabetic patients., Biological Significance: In the present study we have made an attempt to approach the biological and clinical significance of the oxidative and glycoxidative protein damage, in subjects with prediabetes and type-2 diabetes mellitus. AGEs and AOPPs in combination with oxLDL and NOx appear to be important biomarkers for evaluating the association between diabetes and atherosclerotic disorders in aging diabetic patients. More importantly, this cluster of biomarkers that links the short term, "real time" metabolic impairment parameters (NOx, serum glucose, HOMA-IR, serum lipid profile) and the "metabolic memory" markers resulting from the long-term hyperglycemia and hyperlipidemia-induced oxidative stress (HbA1c, AGEs, AOPPs and oxLDL), could be valuable in predicting not only vascular complications in T2DM, but also the onset of diabetes, hence enabling therapeutic interventions from the early stages of diabetes. This article is part of a Special Issue entitled: Posttranslational Protein modifications in biology and Medicine., (Copyright © 2013 Elsevier B.V. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
50. Lipid peroxidation due to in vitro and in vivo exposure of biological samples to nanoparticles.
- Author
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Dinischiotu A, Stanca L, Gradinaru D, Petrache SN, Radu M, and Serban AI
- Subjects
- Animals, Calibration, Carps, Cell Culture Techniques, Cells, Cultured, Erythrocytes metabolism, Humans, Liver metabolism, Malondialdehyde metabolism, Muscle, Skeletal metabolism, Oxidative Stress, Reference Standards, Spectrometry, Fluorescence standards, Lipid Peroxidation, Malondialdehyde chemistry, Quantum Dots toxicity
- Abstract
The increasing use of nanomaterials in biological applications raises numerous concerns about the dangers they might pose to living organisms. The rise in oxidative stress is usually the most readily observed effect induced by nanoparticles, with the measurement of lipid peroxidation levels being one of the most frequently used biological markers for its evaluation. Here, we describe the spectrophotometric and fluorimetric methods for determining the modifications of the malondialdehyde (MDA) level induced by many types of nanoparticles in in vitro and in vivo biological systems.
- Published
- 2013
- Full Text
- View/download PDF
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