Effects of smoking on the salivary and GCF levels of IL-17 and IL-35 in periodontitis.

Periodontitis progression is associated with a host response in which anti-inflammatory and pro-inflammatory cytokine networks play a key role. Smoking is involved in the production of various mediators. The study aims to evaluate the levels of IL-17 and IL-35 in saliva and gingival crevicular fluid (GCF), to investigate the effects of smoking on these cytokines in smoker and non-smoker periodontitis patients. 19 smokers with periodontitis, 20 non-smokers with periodontitis, and 18 periodontally healthy subjects were included in the study. Periodontal clinical indexes were recorded and the levels of IL-17 and IL-35 in saliva and GCF were analyzed. No significant difference was detected among the groups in terms of salivary IL-17 and IL-35 levels. GCF IL-17 and IL-35 concentration levels in the non-smoker periodontitis group were significantly lower than the others (p < 0.05). Total levels of GCF IL-17 were significantly higher in both periodontitis groups than the control group; and total levels of GCF IL-35 were significantly higher in non-smoker periodontitis group than the others (p < 0.05). A positive correlation was detected between the salivary IL-17 and IL-35 levels (r = 0.884), GCF IL-17 and IL-35 concentrations (r = 0.854), and total GCF IL-17 and IL-35 (r = 0.973) levels (p < 0.01). The present study revealed a positive correlation between the IL-35 and IL-17 levels both in saliva and GCF. IL-17 and IL-35 can be considered as one of the cytokines that play a role in periodontal health and periodontitis; and smoking may be among the factors that affect the levels of these cytokines in GCF and saliva.

Correction: Serial measurement of cytokines strongly predict COVID-19 outcome.

[This corrects the article DOI: 10.1371/journal.pone.0260623.].

Evaluation of long-term antibody kinetics in healthcare workers vaccinated with inactivated COVID-19 Vero cell vaccine (CoronaVac), a propensity score-matched observational study.

OBJECTIVES: This study aimed to evaluate the long-term antibody kinetics after vaccinating with an inactivated COVID-19 Vero cell vaccine (CoronaVac) in healthcare workers (HCWs) at a single center in Turkey. METHODS: For this prospective observational study, Chemiluminescence immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA) were used for the determination of binding antibodies (bAb) and neutralizing antibodies (nAb), respectively. Antibody kinetics were compared for the potential influencing factors, and propensity score analysis was performed to match the subcohort for age. RESULTS: Early bAb and nAb response was achieved in all 343 participants. Titers of bAbs against SARS-CoV-2 on 42 days post-vaccination (dpv) were higher in HCWs who were aged <40 years and who had a history of COVID-19. SARS-CoV-2 bAb levels in HCWs on days 42 (n = 97), 90 (n = 97), and 180 (n = 97) were 175 IU/ml (3.9-250), 107 IU/ml (2.4-250), and 66.1 IU/ml (2.57-250), respectively (p<0.001). SARS-CoV-2 bAb (p<0.001) and nAb (p<0.001) titers decreased significantly over time. There was a high negative correlation between SARS-CoV-2 antibody titers and inverse optic density of nAb responses (Pearson correlation coefficient: -0.738, p<0.001). CONCLUSIONS: When the antibody responses were compared, it was seen that the vaccine immunogenicity was better in those who had prior COVID-19 history and were aged <40 years. In the course of time, it was determined that there was a significant decrease in bAb and nAb responses after the 90th day. These results may guide approval decisions for booster COVID-19 vaccines.

Toxicological aspect of bioinsecticide pyrethrum extract and expressions of apoptotic gene levels in human hepotacellular carcinoma HepG2 cells.

Pyrethrum extract (PE), an important natural bioinsecticide, is extensively used across the world to control pest insects in homes and farms. The aim of this study was to evaluate the potential cytotoxic effect of PE using MTT assay and genotoxic effect using micronucleus (MN) assay. The changes in the expressions of the apoptosis genes in mRNA levels were also investigated using Real-Time qPCR analysis as well as the ratio of apoptotic/necrotic cells with AnnexinV-FITC/Propidium iodide (PI) assay in HepG2 cells. PE markedly suppressed the cell proliferation on HepG2 cells. It significantly increased the frequency of micronucleus (MN) at 500 and 1000 µg/mL. PE also induced the percentage of the cell population of late apoptotic/necrotic cells (FITC + PI+) and necrotic cells (FITC- PI+), especially at 4000 µg/mL analyzed by flow cytometry. PE caused significant fold changes in the expression of several apoptotic genes including APAF1, BIK, BAX, BAD, BID, MCL-1, CASP3, CASP1, CASP2, FAS, FADD and TNFRSF1A. In particular, the pro-apoptotic gene Hrk (Harakiri) remarkably and dose-dependently was overexpressed of the mRNA level. As a result, PE may exhibit cyto-genotoxic effects, especially at higher concentrations and lead to significant changes in the expression of mRNA levels in several apoptotic genes.HighlightsNatural bioinsecticide PE exhibited a cytotoxic effect in HepG2 cells.PE significantly induced the micronucleus (MN) frequency at 500 and 1000 µg/mL.This bioinsecticide induced cell death and it lead to significant fold changes in the expression of mRNA levels in several apoptotic genes in HepG2 cells.The highest increase of the expression of mRNA levels was determined in Hrk (Harakiri) at 4000 µg/mL.

Serial measurement of cytokines strongly predict COVID-19 outcome.

PURPOSE: Cytokines are major mediators of COVID-19 pathogenesis and several of them are already being regarded as predictive markers for the clinical course and outcome of COVID-19 cases. A major pitfall of many COVID-19 cytokine studies is the lack of a benchmark sampling timing. Since cytokines and their relative change during an infectious disease course is quite dynamic, we evaluated the predictive value of serially measured cytokines for COVID-19 cases. METHODS: In this single-center, prospective study, a broad spectrum of cytokines were determined by multiplex ELISA assay in samples collected at admission and at the third day of hospitalization. Appropriateness of cytokine levels in predicting mortality were assessed by receiver-operating characteristic (ROC) analyses for both sampling times in paralel to conventional biomarkers. RESULTS: At both sampling points, higher levels of IL-6, IL-7, IL-10, IL-15, IL-27 IP-10, MCP-1, and GCSF were found to be more predictive for mortality (p<0.05). Some of these cytokines, such as IL-6, IL-10, IL-7 and GCSF, had higher sensitivity and specificity in predicting mortality. AUC values of IL-6, IL-10, IL-7 and GCSF were 0.85 (0.65 to 0.92), 0.88 (0.73 to 0.96), 0.80 (0.63 to 0.91) and 0.86 (0.70 to 0.95), respectively at hospital admission. Compared to hospital admission, on the 3rd day of hospitalization serum levels of IL-6 and, IL-10 decreased significantly in the survivor group, unlike the non-survivor group (IL-6, p = 0.015, and IL-10, p = 0.016). CONCLUSION: Our study results suggest that single-sample-based cytokine analyzes can be misleading and that cytokine levels measured serially at different sampling times provide a more precise and accurate estimate for the outcome of COVID-19 patients.

Is Ramadan fasting correlated with disordered eating behaviours in adolescents?

This study aimed to examine the cross-sectional relationship between Ramadan fasting as a spiritual factor with prolonged hunger and disordered eating behaviors. The study was conducted in June 2016 (11th-29th days of Ramadan) and consisted of 238 fasting and 49 non-fasting adolescents. Risk of disordered eating was evaluated using the Eating Attitudes Test-26 (EAT-26) and Three Factor Eating Questionnaire-R18 (TFEQ-R18). Body image dissatisfaction was rated with Stunkard's Figure Rating Scale (FRS). Nutritional status was assessed using a 24-hour dietary recall. There was no significant difference between energy intake, EAT-26 and TFEQ-R18 scores (except the emotional eating sub-scores) between the groups. FRS revealed that the comparisons of their "ideal" and self were not significantly different between the groups whereas the gap between the figures they think healthy and closest to self was significantly higher amongst non-fasting adolescents. Two-hundred and two (97.5%) adolescents reported fasting for religious purposes whereas only 8 (3.4%) for losing weight. The EAT-26 total scores were in the pathological range in 39 (16.8%) adolescents who fasted for religious purposes. This study suggests that motivation of adolescents to fast during Ramadan was due to spiritual decisions rather than weight control or other factors and Ramadan fasting was not correlated with disordered eating behaviors or body image dissatisfaction.

Prognostic importance of markers for inflammation, angiogenesis and apoptosis in high grade glial tumors during temozolomide and radiotherapy.

INTRODUCTION: Angiogenesis, inflammation and apoptosis have an important place in the carcinogenesis of high-grade gliomas (HGG). We evaluated the postoperative levels and the prognostic importance of tumor necrosis factor-alpha (TNFα), interleukin 6 (IL6), endoglin (CD105), vascular endothelial growth factor (VEGF), M65 and M30 as markers of inflammation, angiogenesis and apoptosis in patients with HGG. METHODS AND RESULTS: Postoperative pretreatment sera were collected from 44 newly diagnosed patients with HGG. The control group was also consisted of 44 healthy people. The median age of all patients with HGG was 59 (range: 30-80). Temozolomide concurrent with radiotherapy was given to 37 patients. Thereafter 24 patients received consolidation temozolomide monotherapy. Mean chemotherapy cycle was 4.2. Progression free survival and overall survival were 6 (95% CI; 5.16-6.83) and 16 months (95% CI; 13.07-18.93) respectively in patients treated with concurrent chemoradiotherapy and consolidation chemotherapy. Relative to the control cohort endoglin (p = 0.000) and TNFα (p = 0.000) levels were significantly lower; however VEGF (p = 0.030) levels were higher in the patient group. In contrast, there were no significant change in IL-6 levels and the plasma apoptotic markers M65 (p = 0.085) and M30 (p = 0.292). In separate log rank tests, these biological markers did not correlate with survival. DISCUSSION AND CONCLUSION: In HGG, a significant decrease in endoglin and TNFα levels was observed, while VEGF levels were significantly increased postoperatively. However, with the power from this patient population, no correlation with survival was observed.

The effect of maternal serum sFAS/sFASL system on etiopathogenesis of preeclampsia and severe preeclampsia.

Abstract Objective: The objective of the study is to evaluate whether there is a difference in serum soluble free acid synthesis (sFas)/sFasL levels between patients with preeclampsia, severe preeclampsia and normal healthy pregnancy. Methods: This is a case control study comparing serum sFas and sFasL concentrations in patients with mild preeclampsia (n=26) and patients with severe preeclampsia (n=22) in the second and the third trimester pregnancy to normal healthy pregnant controls (n=21). Maternal serum sFas and sFasL was collected at the time of diagnosis of preeclampsia or severe preeclampsia and obtained using ELISA assay. The control group's characteristics of gestational age, maternal age, BMI, parity, smoking status, and history of hypertension were matched with the study groups. While evaluating the results, mean±SD for quantitaive data, the statistical methods of Kruskal Wallis and Mann-Whitney U tests for comparements between groups were used. Results: Maternal mean serum levels of sFas and sFasL were evaluated and statistical difference was not found in both preeclamptic pregnancies (846,65±96,74pg/ml and 17,48±15.60 pg/ml) and severe preeclamptic pregnancies ( 864,29±106,30 pg/ml and 99,92±336,69 pg/ml) versus control group (830,58±127,21 pg/ml and 30,13±22,69 pg/ml). For all demographic characteristics, there was also no statistical difference between study groups and control group. Conclusions: The finding of this study showed no difference in maternal serum levels of sFas and sFasL in preeclampsia and severe preeclampcia versus control group.

TSH-induced gene expression involves regulation of self-renewal and differentiation-related genes in human bone marrow-derived mesenchymal stem cells.

Bone marrow-derived mesenchymal stem cells are pluripotent cells that are capable of differentiating into a variety of cell types including neuronal cells, osteoblasts, chondrocytes, myocytes, and adipocytes. Despite recent advances in stem cell biology, neuroendocrine relations, particularly TSH interactions remain elusive. In this study, we investigated expression and biological consequence of TSH receptor (TSHR) interactions in mesenchymal stem cells of cultured human bone marrow. To the best of our knowledge, we demonstrated for the first time that human bone marrow-derived mesenchymal stem cells expressed a functional thyrotropin receptor that was capable of transducing signals through cAMP. We extended this study to explore possible pathways that could be associated directly or indirectly with the TSHR function in mesenchymal stem cells. Expression of 80 genes was studied by real-time PCR array profiles. Our investigation indicated involvements of interactions between TSH and its receptor in novel regulatory pathways, which could be the important mediators of self-renewal, maintenance, development, and differentiation in bone marrow-derived mesenchymal stem cells. TSH enhanced differentiation to the chondrogenic cell lineage; however, further work is required to determine whether osteoblastic differentiation is also promoted. Our results presented in this study have opened an era of regulatory events associated with novel neuroendocrine interactions of hypothalamic-pituitary axis in mesenchymal stem cell biology and differentiation.

Establishment of a primary pleomorphic xanthoastrocytoma cell line: in vitro responsiveness to some chemotherapeutics.

BACKGROUND: Anaplastic pleomorphic xanthoastrocytoma is an aggressively growing, malignant, and eventually fatal tumor of the central nervous system. Testing chemotherapeutic drug sensitivity under in vitro conditions would be a useful strategy to determine sensitive or resistant drugs for fatal brain cancers. OBJECTIVE: To establish primary cell cultures of excised tumor tissue from pleomorphic xanthoastrocytoma-bearing patients and to test their sensitivity against various anticancer chemotherapy drugs. METHODS: Prepared suspensions of the excised tumor tissue from a patient who had a recurrent grade 3 pleomorphic xanthoastrocytoma was cultured in culture dishes until cells began to grow. Immunofluorescent and immunohistochemical visualizations were performed using confocal and light microscopy. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay in comparison with ³H-thymidine incorporation assay was used to test cellular toxicity of several anticancer drugs. RESULTS: We established vigorously growing primary cells of the tumor. Drug sensitivity testing was conducted successfully. CONCLUSION: Primary cell cultures of surgically removed tumor tissues may be useful in studies of cancer biology and chemotherapeutic drug sensitivity for recurrent malignant brain tumors, particularly for anaplastic pleomorphic xanthoastrocytoma.