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    Association of serum ADMA, SDMA and L-NMMA concentrations with disease progression in COVID-19 patients
    (NLM (Medline), 2023) Haşimi, Adnan; Doğan, Özlem; Ceran Serdar, Ceyhan; Serdar, Muhittin Abdulkadir
    Introduction: This study determines and compares the concentrations of arginine and methylated arginine products ((asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), n-monomethyl-1-arginine (L-NMMA) and homoarginine (HA)) for assessment of their association with disease severity in serum samples of COVID-19 patients. Materials and methods: Serum arginine and methylated arginine products of 57 mild-moderate and 29 severe (N = 86) COVID-19 patients and 21 controls were determined by tandem mass spectrometry. Moreover, the concentrations of some of the routine clinical laboratory parameters -neutrophil lymphocyte ratio (NLR), C-reactive protein, ferritin, D-dimer, and fibrinogen measured during COVID-19 follow-up were also taken into consideration and compared with the concentrations of arginine and methylated arginine products. Results: Serum ADMA, SDMA and L-NMMA were found to be significantly higher in severe COVID-19 patients, than in both mild-moderate patients and the control group (P < 0.001 for each). In addition, multiple logistic regression analysis indicated L-NMMA (cut-off =120 nmol/L OR = 34, 95% confidence interval (CI) = 3.5-302.0, P= 0.002), CRP (cut-off = 32 mg/L, OR = 37, 95% CI = 4.8-287.0, P < 0.001), and NLR (cut-off = 7, OR = 22, 95% CI = 1.4-335.0, P = 0.020) as independent risk factors for identification of severe patients. Conclusions: The concentration of methylated arginine metabolites are significantly altered in COVID-19 disease. The results of this study indicate a significant correlation between the severity of COVID-19 disease and concentrations of CRP, NLR and L-NMMA. Croatian Society of Medical Biochemistry and Laboratory Medicine.
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    Does smoking influence tryptophan metabolism in periodontal inflammation? A cross-sectional study
    (John Wiley and Sons Inc, 2023) Önder, Canan; Akdoğan, Nihan; Kurgan, Şivge; Balcı, Nur; Serdar, Ceyhan Ceran; Ceran Serdar, Ceyhan; Serdar, Muhittin Abdulkadir; Günhan, Meral
    ObjectivesThe aim of this study was to identify the effects of smoking and periodontal inflammation on tryptophan-kynurenine metabolism as well as the correlation between these findings and clinical periodontal parameters. BackgroundIt has been shown that the tryptophan amino acid's primary catabolic pathway, the kynurenine pathway (KP), may serve as a key biomarker for periodontal disease. Although there are studies investigating the effect of smoking on KYN-TRP metabolism, the effect of smoking on periodontal disease through KP has not been revealed so far. MethodsThe salivary and serum samples were gathered from 24 nonsmoker (NS-P) stage III, grade B generalized periodontitis and 22 smoker (S-P) stage III, grade C generalized periodontitis patients, in addition to 24 nonsmoker (NS-C) and 24 smoker (S-C) periodontally healthy control individuals. Saliva and serum IL-6, kynurenine (KYN), and tryptophan (TRP) values, and KYN/TRP ratio were analyzed by liquid chromatography-mass spectrometry. Clinical periodontal measurements were recorded. ResultsSalivary TRP values were significantly higher in both periodontitis groups than control groups (p < .05). Salivary KYN values were highest in NS-P group (p < .05). Salivary KYN values did not differ significantly between periodontitis groups (p = .84). Salivary KYN/TRP ratio was significantly lower in NS-P group compared to other groups (p < .001). Serum TRP value is higher in S-P group than other groups; however, significant difference was found in S-C group (p < .05). Serum KYN values were significantly lower in smokers than nonsmokers. Serum KYN/TRP ratio is higher in NS-P group. NS-P group has the highest salivary IL-6 levels, NS-C group has the lowest values (p < .05). ConclusionsOur results point out that smoking exacerbates inflammation in the periodontium and increases TRP destruction and decreases IDO activity by suppressing KP in serum. As a result, kynurenine and its metabolites may be significant biomarkers in the link between smoking and periodontal disease.
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    Free amino acid composition of saliva in patients with healthy periodontium and periodontitis
    (Springer Heidelberg, 2021) Balcı, Nur; Kurgan, Şivge; Çekici, Ali; Çakır, Tülin; Serdar, Muhittin Abdulkadir
    Objectives To identify and compare the free amino acids in the saliva of periodontitis patients and healthy individuals and to assess their levels in different periodontal disease types. Materials and methods There were three groups: healthy individuals (control (C); n = 20), Stage III Grade B generalized periodontitis (GP-B; n = 20), and Stage III Grade C generalized periodontitis (GP-C; n = 20). Clinical periodontal parameters were measured. Amino acid analysis of the saliva was accomplished by liquid chromatography-mass spectrometry (LC MS/MS), taking the mean concentration. Results Citrulline and carnosine concentrations were significantly higher in patients with periodontitis than in the control group (p < 0.017). Methionine, glutamic acid, and arginine showed significantly higher concentrations in GP-C, whereas proline and tryptophan showed higher concentrations in the GP-B group (p < 0.017). There was a significant correlation between methionine, citrulline, arginine, and carnosine and clinical periodontal parameters. Conclusions Our results demonstrate that periodontal status and disease type can result in variations in salivary amino acid (AA) content in correlation with clinical inflammatory signs. The significant correlation of methionine, citrulline, carnosine, and arginine with clinical parameters, regardless of systemic status, suggests that the levels of different salivary free AAs play roles in periodontitis.
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    Influence of periodontal inflammation on tryptophan-kynurenine metabolism: A cross-sectional study
    (Springer Heidelberg, 2022) Kurgan, Şivge; Önder, Canan; Balcı, Nur; Akdoğan, Nihan; Altıngöz, Sema Merve; Serdar, Muhittin Abdulkadir; Günhan, Meral
    Objectives Kynurenine pathway (KP) is the primary way of degrading tryptophan (TRP) and generates several bioactive metabolites (such as kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxykynurenine (3OHKYN)) to regulate biological processes that include host-microbiome signaling and immune cell response. This study is aimed to determine the relationship between periodontal inflammation and tryptophan-kynurenine metabolism and identify their association with periodontal clinical parameters. Materials and methods Saliva and serum samples were collected from 20 stage III, grade B generalized periodontitis patients, and 20 periodontally healthy control individuals. Samples were analyzed for IL-6, KYN, TRP, KYN/TRP ratio, KYNA, 3OHKYN, picolinic acid (PA), and quinolinic acid (QA) by liquid chromatography-mass spectrometry. Clinical periodontal parameters (plaque index (PI), probing pocket depth (PPD), gingival recession (GR), clinical attachment loss (CAL), and bleeding on probing (BOP)) were recorded. Results Clinical parameters were significantly higher in the periodontitis group (p < 0.001). Salivary IL-6, TRP, KYN, KYNA, PA, and QA levels were significantly higher and KYN/TRP ratio was significantly lower in periodontitis group than control group (p < 0.05). Serum KYN, KYN/TRP ratio and PA levels were significantly higher in periodontitis group than control group (p < 0.05). PPD, BOP, PI, and CAL had significantly positive correlations with salivary IL-6, TRP, PA, QA, and serum KYN and significantly negative correlations with salivary KYN/TRP ratio. Conclusions Our results suggest that periodontal inflammation plays a role in local and systemic tryptophan-kynurenine metabolism.
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    Oxidative stress and foxo-1 relationship in stage iii periodontitis
    (2024) Gürbüz, Elif Selin; Güney, Zeliha; Kurgan, Şivge; Balcı, Nur; Serdar, Muhittin Abdulkadir; Günhan, Meral
    Objectives: 8-Hydroxideoxyguanosine (8-OHdG) is a marker of oxidative stress, and Forkhead Box-O1 (FOXO1) is a transcription factor and signaling integrator in cell and tissue homeostasis. This study aims to determine FOXO1 and 8-OHdG levels in serum and saliva samples of periodontitis patients and to evaluate their relationship with clinical periodontal parameters. Materials and Methods: Twenty healthy individuals, twenty generalized Stage III Grade B periodontitis patients, and nineteen generalized Stage III Grade C periodontitis patients were included in the study. Clinical periodontal parameters (plaque index (PI), probing depth (PD), bleeding on probing (BOP), and clinical attachment level (CAL)) were recorded. Salivary and serum 8-OHdG and FOX-O1 levels were analyzed by enzyme-linked immunosorbent assay (ELISA). Results: Clinical periodontal parameters showed a statistically significant increase in periodontitis groups compared to the control group (p < 0.05). 8-OHdG salivary levels were significantly higher in both periodontitis groups compared to the control group. The salivary FOXO1 levels were significantly lower in both periodontitis groups compared to the control group. Salivary FOXO1 level had a low-grade negative correlation with BOP and salivary 8-OHdG level. Conclusions: While reactive oxygen species increase in periodontal inflammation, low expression of FOXO1, an important transcription factor for antioxidant enzymes, supports that this molecule plays a vital role in tissue destruction, and FOXO1 can be seen as a potential immune modulator. Clinical relevance: The role of FOXO1 in supporting antioxidant defense may suggest that FOXO1 is a candidate target for periodontitis treatment.
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    Potential biomarkers reflecting inflammation in patients with severe periodontitis: Fractalkine (CX3CL1) and its receptor (CX3CR1)
    (Wiley, 2021) Balcı, Nur; Çekici, Ali; Kurgan, Şivge; Şahinkaya, Selin; Serdar, Muhittin Abdulkadir
    Objective The aim of this study was to determine differences in GCF and serum levels of fractalkine/CX3CL1 and its receptor/ CX3CR1 between the patients with stage III/grade B periodontitis and periodontally healthy subjects. Background Fractalkine (CX3CL1), the only member of CX3C chemokine family, is involved in the pathogenesis of several systemic inflammatory diseases' disorders including rheumatoid arthritis, cardiovascular diseases, tonsillitis, and diabetes mellitus. It has critical functions in inflammatory cell migration, adhesion, and proliferation. Methods 20 stage III/grade B periodontitis (P) and 20 healthy individuals (control; C) were included in this clinical study (all never smokers and systemically healthy). Clinical periodontal parameters were measured. Serum and GCF levels of CX3CL1, CX3CR1, and IL-1 beta were quantified by enzyme-linked immunosorbent assay and reported as total amounts and concentration. Results The GCF concentrations and also total amount of CX3CL1, CX3CR1, and IL-1 beta were statistically significantly higher in the patients with periodontitis compared with control group (P < 0.05). CX3CL1, CX3CR1, and IL-1 beta levels in the GCF were significantly and positively correlated with all the clinical periodontal parameters (PI, PPD, BOP, and CAL; P < 0.01, P < 0.05). There was a significant correlation between IL-1 beta, CX3CL1, and CX3CR1 concentrations in the GCF (respectively; r = 0.838 and r = 0.874, P < 0.01). Conclusion Fractalkine and its receptor may play role in mechanisms through the regulation of inflammation or on the pathogenesis of periodontal disease.