Oxidative Stress and FOXO-1 Relationship in Stage III Periodontitis.

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.

Longitudinal non-targeted metabolomic profiling of urine samples for monitoring of kidney transplantation patients.

The assessment of kidney function within the first year following transplantation is crucial for predicting long-term graft survival. This study aimed to develop a robust and accurate model using metabolite profiles to predict early long-term outcomes in patient groups at the highest risk of early graft loss. A group of 61 kidney transplant recipients underwent thorough monitoring during a one-year follow-up period, which included a one-week hospital stay and follow-up assessments at three and six months. Based on their 12-month follow-up serum creatinine levels: Group 2 had levels exceeding 1.5 mg/dl, while Group 1 had levels below 1.5 mg/dl. Metabolites were detected by mass spectrometer and first pre-processed. Univariate and multivariate statistical analyses were employed to identify significant differences between the two groups. Nineteen metabolites were found to differ significantly in the 1st week, and seventeen metabolites in the 3rd month (adjusted p-value < 0.05, quality control (QC) < 30, a fold change (FC) > 1.1 or a FC < 0.91, Variable Influence on Projection (VIP) > 1). However, no significant differences were observed in the 6th month. These distinctive metabolites mainly belonged to lipid, fatty acid, and amino acid categories. Ten models were constructed using a backward conditional approach, with the best performance seen in model 5 for Group 2 at the 1st-week mark (AUC 0.900) and model 3 at the 3rd-month mark (AUC 0.924). In conclusion, the models developed in the early stages may offer potential benefits in the management of kidney transplant patients.

Wnt signaling in periodontitis.

OBJECTIVE: This study aimed to evaluate the Wnt/ß-catenin signaling pathway activity in gingival samples obtained from patients with periodontitis. MATERIALS AND METHODS: Fifteen patients with stage III grade B (SIIIGB) and eleven with stage III grade C (SIIIGC) periodontitis were included and compared to 15 control subjects. ß-Catenin, Wnt 3a, Wnt 5a, and Wnt 10b expressions were evaluated by Q-PCR. Topographic localization of tissue ß-catenin, Wnt 5a, and Wnt 10b was measured by immunohistochemical analysis. TNF-α was used to assess the inflammatory state of the tissues, while Runx2 was used as a mediator of active destruction. RESULTS: Wnt 3a, Wnt 5a, and Wnt 10b were significantly higher in gingival tissues in both grades of stage 3 periodontitis compared to the control group (p < 0.05). ß-Catenin showed intranuclear staining in connective tissue in periodontitis, while it was confined to intracytoplasmic staining in epithelial tissue and the cell walls in the control group. Wnt5a protein expression was elevated in periodontitis, with the most intense staining observed in the connective tissue of SIIIGC samples. Wnt10b showed the highest density in the connective tissue of patients with periodontitis. CONCLUSIONS: Our findings suggested that periodontal inflammation disrupts the Wnt/ß-catenin signaling pathway. CLINICAL RELEVANCE: Periodontitis disrupts Wnt signaling in periodontal tissues in parallel with tissue inflammation and changes in morphology. This change in Wnt-related signaling pathways that regulate tissue homeostasis in the immunoinflammatory response may shed light on host-induced tissue destruction in the pathogenesis of the periodontal disease.

Bridging the Gap between Gut Microbiota and Alzheimer's Disease: A Metaproteomic Approach for Biomarker Discovery in Transgenic Mice.

Alzheimer's Disease (AD) is a progressively debilitating form of dementia that affects millions of individuals worldwide. Although a vast amount of research has investigated the complex interplay between gut microbiota and neurodegeneration, the metaproteomic effects of microbiota on AD pathogenesis remain largely uncharted territory. This study aims to reveal the role of gut microbiota in AD pathogenesis, particularly regarding changes in the proteome and molecular pathways that are intricately linked to disease progression. We operated state-of-the-art Nano-Liquid Chromatography Mass Spectrometry (nLC-MS/MS) to compare the metaproteomic shifts of 3-month-old transgenic (3M-ALZ) and control (3M-ALM, Alzheimer's Littermate) mice, depicting the early onset of AD with those of 12-month-old ALZ and ALM mice displaying the late stage of AD. Combined with computational analysis, the outcomes of the gut-brain axis-focused inquiry furnish priceless knowledge regarding the intersection of gut microbiota and AD. Accordingly, our data indicate that the microbiota, proteome, and molecular changes in the intestine arise long before the manifestation of disease symptoms. Moreover, disparities exist between the normal-aged flora and the gut microbiota of late-stage AD mice, underscoring that the identified vital phyla, proteins, and pathways hold immense potential as markers for the early and late stages of AD. Our research endeavors to offer a comprehensive inquiry into the intricate interplay between gut microbiota and Alzheimer's Disease utilizing metaproteomic approaches, which have not been widely adopted in this domain. This highlights the exigency for further scientific exploration to elucidate the underlying mechanisms that govern this complex and multifaceted linkage.

Sepsis biomarkers for early diagnosis of bacteremia in emergency department.

INTRODUCTION: We compared the diagnostic values of individual and composite biomarkers used in the prediction of bacteremia in adult emergency department patients. METHODOLOGY: First-hour blood levels of C- reactive protein, procalcitonin, interleukin-6, lactate, lipopolysaccharide-binding protein and white blood cell count were collected from a 30-person control group and 47 adult patients. Patients included in this study were admitted to the emergency department on suspicion of sepsis. We categorized patients according to presence/absence of sepsis and bacteremia. Our control group was categorized as S-B -, septic patients with bacteremia were S+B+, and septic patients without bacteremia were S+B-. RESULTS: All biomarkers showed a statistically significant elevation when S+B- and S+B+ groups were compared with the S-B-. When S+B+ group was compared with the S+B- group only procalcitonin and lactate levels had statistically significant elevation (p < 0.005). Regression analysis demonstrated that lactate and procalcitonin were independently associated with having bacteremia in the state of sepsis and Hosmer-Lemeshow score was 0.772. The areas under the curve (AUC) values of biomarkers procalcitonin, lactate, C-reactive protein, combined 1 (procalcitonin+ lactate), and combined 2 (procalcitonin + lactate + C-reactive protein) were 0.773, 0.744, 0.523, 0.806, and 0.829 respectively. CONCLUSIONS: Combination of tests such as combined 1 or combined 2 were highly predictive of bacteremia in adult septic patients. Combined 2 demonstrated the best predictive performance and could be utilized as a tool to assist diagnosis of bacteremia before culture results are available.

Meta-analysis of hearing outcomes of chronic otitis media surgery in the only hearing ear.

OBJECTIVE: To assess the hearing outcomes of surgery for patients with chronic otitis media (COM) with or without cholesteatoma in case of the only hearing ear (OHE). METHODS: This meta-analysis included COM patients with hearing in only one ear. The PubMed, Scopus, and Cochrane databases were reviewed. RESULTS: Thirteen studies were included, 252 excluded. The total number of operated ears was 229. The patients' ages ranged from 6 to 78 years. A change greater than 10 dB in hearing thresholds in the OHE was considered as a significant result. When both the COM with (cCOM) and without cholesteatoma (ncCOM) cases were considered, the air bone gap (ABG), air conduction (AC) and bone conduction (BC) thresholds were stable or improved in 91.06% (95% CI:81.94-97.19%), 87.91% (82.14-92.34%), and 94.99% (95% CI:90.20-97.97%) of patients, respectively. Stable or improved ABG, AC and BC thresholds were observed in 92.36% (95% CI:81.67-97.86%), 87.36% (95% CI:71.46-96.23%), and 94.85% (95% CI:81.36-99.49%) of those with ncCOM, respectively. For patients with cCOM, the results were 85.96% (95% CI:81.36-99.49%), 85.20% (95% CI:76.04-91.87%), and 97.01% (95% CI:89.62-99.63%), respectively. There were no significant differences in these thresholds between either category. CONCLUSION: Hearing deterioration in AC and BC thresholds can be expected in about 13-15% and 5-3%, respectively, of patients, with ncCOM or cCOM. Our results should not be construed as a guide for determining surgery eligibility in patients with COM in the OHE.

A new haematocytometric index: Predicting severity and mortality risk value in COVID-19 patients.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 virus, is a major public health concern spanning from healthy carriers to patients with life-threatening conditions. Although most of COVID-19 patients have mild-to-moderate clinical symptoms, some patients have severe pneumonia leading to death. Therefore, the early prediction of disease prognosis and severity is crucial in COVID-19 patients. The main objective of this study is to evaluate the haemocytometric parameters and identify severity score associated with SARS-CoV-2 infection. METHODS: Clinical and laboratory records were retrospectively reviewed from 97 cases of COVID-19 admitted to hospitals in Istanbul, Turkey. The patient groups were subdivided into three major groups: Group 1 (Non-critical): 59 patients, Group 2 (Critical-Survivors): 23 patients and Group 3 (Critical-Non-survivors):15 patients. These data was tested for correlation, including with derived haemocytometric parameters. The blood analyses were performed the Sysmex XN-series automated hematology analyser using standard laboratory protocols. All statistical testing was undertaken using Analyse-it software. RESULTS: 97 patients with COVID-19 disease and 935 sequential complete blood count (CBC-Diff) measurements (days 0-30) were included in the final analyses. Multivariate analysis demonstrated that red cell distribution width (RDW) (>13.7), neutrophil to lymphocyte ratio (NLR) (4.4), Hemoglobin (Hgb) (<11.4 gr/dL) and monocyte to neutrophil ratio (MNR) (0.084) had the highest area under curve (AUC) values, respectively in discrimination critical patients than non-critical patients. In determining Group 3, MNR (<0.095), NLR (>5.2), Plateletcount (PLT) (>142 x103/L) and RDW (>14) were important haemocytometric parameters, and the mortality risk value created by their combination had the highest AUC value (AUC = 0.911, 95% CI, 0886-0.931). Trend analysis of CBC-Diff parameters over 30 days of hospitalization, NLR on day 2, MNR on day 4, RDW on day 6 and PLT on day 7 of admission were found to be the best time related parameters in discrimination non-critical (mild-moderate) patient group from critical (severe and non-survivor) patient group. CONCLUSION: NLR is a strong predictor for the prognosis for severe COVID-19 patients when the cut-off chosen was 4.4, the combined mortality risk factor COVID-19 disease generated from RDW-CV, NLR, MNR and PLT is best as a mortality haematocytometric index.

Endocan (ESM-1) levels in gingival crevicular fluid correlate with ICAM-1 and LFA-1 in periodontitis

Abstract: Endocan, a 50 kDa soluble proteoglycan, also called endothelial cell-specific molecule-1 (ESM-1), is involved in many major cellular activities and has been reported to be overexpressed in inflammatory conditions. This study aims to determine ESM-1 levels in gingival crevicular fluid (GCF) samples from individuals with periodontitis to determine the correlation between the levels of lymphocyte-function-associated antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM-1), and clinical findings of periodontitis. This study enrolled 27 individuals diagnosed with Stage III-Grade C generalized periodontitis and 16 individuals as healthy controls. Bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment loss (CAL) were calculated. Enzyme-linked immunosorbent assay (ELISA) test was used for detecting the levels of ESM-1, ICAM-1, and LFA-1 in GCF samples. PPD, BOP, CAL, and GCF volumes were significantly increased in patients with periodontitis in comparison to the control group (p < 0.001). The total amount of ESM-1, ICAM-1, and LFA-1 levels in GCF were increased in the periodontitis group (p < 0.001). ESM-1 level correlated with PPD, BOP, and CAL (p < 0.05). ICAM-1 level correlated with BOP and CAL (p < 0.05). LFA-1 level correlated with PPD and CAL (p < 0.05). Our data indicate that ESM-1, ICAM-1, and LFA-1 levels are increased in GCF of patients with periodontitis. These molecules could be associated with the pathogenesis and progression of periodontal disease.

Endocan (ESM-1) levels in gingival crevicular fluid correlate with ICAM-1 and LFA-1 in periodontitis.

Endocan, a 50 kDa soluble proteoglycan, also called endothelial cell-specific molecule-1 (ESM-1), is involved in many major cellular activities and has been reported to be overexpressed in inflammatory conditions. This study aims to determine ESM-1 levels in gingival crevicular fluid (GCF) samples from individuals with periodontitis to determine the correlation between the levels of lymphocyte-function-associated antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM-1), and clinical findings of periodontitis. This study enrolled 27 individuals diagnosed with Stage III-Grade C generalized periodontitis and 16 individuals as healthy controls. Bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment loss (CAL) were calculated. Enzyme-linked immunosorbent assay (ELISA) test was used for detecting the levels of ESM-1, ICAM-1, and LFA-1 in GCF samples. PPD, BOP, CAL, and GCF volumes were significantly increased in patients with periodontitis in comparison to the control group (p < 0.001). The total amount of ESM-1, ICAM-1, and LFA-1 levels in GCF were increased in the periodontitis group (p < 0.001). ESM-1 level correlated with PPD, BOP, and CAL (p < 0.05). ICAM-1 level correlated with BOP and CAL (p < 0.05). LFA-1 level correlated with PPD and CAL (p < 0.05). Our data indicate that ESM-1, ICAM-1, and LFA-1 levels are increased in GCF of patients with periodontitis. These molecules could be associated with the pathogenesis and progression of periodontal disease.

Relationship of periodontitis and edentulism to angiographically diagnosed coronary artery disease: A cross-sectional study.

OBJECTIVE: The objective of the study is to examine the connection between oral status and the extent of coronary artery disease (CAD), which is diagnosed by angiography. BACKGROUND: Periodontitis and tooth loss have been linked to atherosclerosis and CAD in previous studies. However, no distinct connection was revealed due to the diversity of the results and the variety of diagnostic methods. To provide a more consistent data pool and stronger evidence, there is a need for studies with standard measurements and diagnostic criteria. METHODS: 309 patients, who consulted to Ankara University, Faculty of Medicine, Department of Cardiology and had coronary angiography, were enrolled to this study. Individuals were grouped based on their coronary angiography results, as CAD (+) (n = 233) and CAD (-) (n = 76). Studied parameters included cardiovascular risk factors, plaque index (PI), remaining teeth count, bleeding on probing (BOP), and probing pocket depth (PPD). Periapical radiographs were taken from teeth with ≥4 mm PPD. Oral status was categorized as periodontally healthy subjects/patients with gingivitis (Group 1), patients with periodontitis (Group 2), and edentulous subjects (Group 3). RESULTS: PI (P < 0.001), PPD (P = 0.001), BOP (P = 0.004), the number of patients with less than 10 teeth (P = 0.014), and edentulism (P = 0.009) were significantly higher in CAD (+) patients, who were mostly older (P < 0.001) and male (P < 0.001). Multivariate logistic regression analysis revealed that Group 2 (odds ratio = 2.48, 95% confidence interval = 1.24-4.95, P = 0.010) and Group 3 (odds ratio = 2.01, 95% confidence interval = 1.14-5.17, P = 0.040) were highly associated with CAD. Two and three stenosed vessels were significantly higher in Groups 2 and 3 compared to Group 1 (P = 0.003). CONCLUSIONS: It was found that both edentulism and periodontitis were related to CAD.

The effect of α-tocopherol and selenium on human gingival fibroblasts and periodontal ligament fibroblasts in vitro.

BACKGROUND: The aim of the present study is to evaluate the effect of α-tocopherol and selenium on gingival fibroblasts (GFs) and periodontal ligament fibroblasts (PDLFs) in terms of proliferation, basic fibroblast growth factor (bFGF) release, collagen type I synthesis, and wound healing. METHODS: Primary cultures of human GFs and PDLFs were isolated. Four test groups and a control group free of medication was formed. In group E, 60 µM α-tocopherol was used, and in groups ES1, ES2, and ES3, the combination of 60 µM α-tocopherol with 5 × 10(-9) M, 10 × 10(-9) M, and 50 × 10(-9) M selenium was used, respectively. Viability, proliferation, bFGF, and collagen type I synthesis from both cell types were evaluated at 24, 48, and 72 hours, and healing was compared on a new wound-healing model at 12, 24, 36, 48, and 72 hours. RESULTS: α-Tocopherol alone significantly increased the healing rate of PDLFs at 12 hours and increased bFGF and collagen type I release from GFs and PDLFs at 24, 48, and 72 hours. The α-tocopherol/selenium combination significantly enhanced the proliferation rate of both cells at 48 hours, decreased the proliferation of PDLFs at 72 hours, and increased the healing rate of GFs at 12 hours and PDLFs at 12 and 48 hours. bFGF and collagen type I synthesis was also increased in both cell types at 24, 48, and 72 hours by α-tocopherol/selenium combination. CONCLUSION: α-Tocopherol and α-tocopherol/selenium combination is able to accelerate the proliferation rate and wound-healing process and increase the synthesis of bFGF and collagen type I from both GFs and PDLFs.

Low-level laser irradiation affects the release of basic fibroblast growth factor (bFGF), insulin-like growth factor-I (IGF-I), and receptor of IGF-I (IGFBP3) from osteoblasts.

OBJECTIVE: It was the aim of the present study to evaluate whether the laser irradiation of osteoblasts could enhance the release of growth factors including basic fibroblast growth factor (bFGF), insulin-like growth factor-I (IGF-I), and receptor of IGF-I (IGFBP3). BACKGROUND DATA: Low-level laser therapy (LLLT) has been shown to have biostimulatory effects on various cell types by enhancing production of some cytokines and growth factors. MATERIALS AND METHODS: Human mesenchymal stem cells (MSCs) were seeded in osteogenic medium and differentiated into osteoblasts. Three groups were formed: in the first group (single dose group), osteoblasts were irradiated with laser (685 nm, 25 mW, 14.3 mW/cm(2), 140 sec, 2 J/cm(2)) for one time; and in the second group, energy at the same dose was applied for 2 consecutive days (double dose group). The third group was not irradiated with laser and served as the control group. Proliferation, viability, bFGF, IGF-I, and IGFBP3 levels were compared between groups. RESULTS: Both of the irradiated groups revealed higher proliferation, viability, bFGF, IGF-I, and IGFBP3 expressions than did the nonirradiated control group. There was increase in bFGF and IGF-I expressions and decrease in IGFBP3 in the double dose group compared to single dose group. CONCLUSIONS: The results of the present study indicate that LLLT increases the proliferation of osteoblast cells and stimulates the release of bFGF, IGF-I, and IGFBP3 from these cells. The biostimulatory effect of LLLT may be related to the enhanced production of the growth factors.