Browsing by Subject "tumor necrosis factor"
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Item Comparison of TNF antagonism by etanercept and dexamethasone on airway epithelium and remodeling in an experimental model of asthma(2013) Yilmaz O.; Karaman M.; Bagriyanik H.A.; Firinci F.; Kiray M.; Turkeli A.; Karaman O.; Yuksel H.Background The aim of the study was to compare the influence of TNF antagonism and corticosteroid treatment on epithelial, smooth muscle and basement membrane component of airway remodeling in an experimental murine model of chronic asthma. Methods We used 30 BALB/c mice. Group 1 not exposed to ovalbumin or any medication was designated as control group. Chronic asthma model was achieved in the other three groups with intraperitoneal (IP) and inhaled ovalbumin. Then, Group 2 received IP saline, Group 3 received IP dexamethasone and Group 4 received IP etanercept. Epithelial, subepithelial smooth muscle and basement membrane thickness as well as goblet cells and mast cells were examined on samples isolated from left lung. Results Etanercept treatment led to thinner epithelial and basement membrane layer and lower goblet and mast cell number than untreated asthmatic mice (p < 0.001, p = 0.001, p = 0.005 and p = 0.03 respectively). Neither epithelial and basement membrane thickness nor mast cell number was different among mice treated with etanercept and dexamethasone (p = 0.38, p = 0.79 and p = 0.51 respectively). However, etanercept group was associated with thicker subepithelial muscle layer but lower goblet cell number (p < 0.001 and p = 0.04 respectively) than dexamethasone group. Conclusions Corticosteroids are more effective in decreasing smooth muscle mass while TNF antagonists in reducing goblet cell number in animal model of asthma. Therefore, further research is needed to assess the synergistic use of TNF antagonism and dexamethasone for more rational remodeling control. © 2013 Elsevier B.V.Item Distribution of furin, TNF-α, and TGF-β2 in the endometrium of missed abortion and voluntary first trimester termination case(Science Printers and Publishers Inc., 2015) Ozbilgin K.; Turan A.; Kahraman B.; Atay C.; Vatansever S.; Uluer E.T.; Özçakir T.Objective: To identify the role of furin, TNF-a, and TGF-b2 in human missed abortion pathogenesis. STUDY DESIGN: Decidual materials were collected from patients diagnosed with a missed abortion (n=10) (missed abortion group) and from legal voluntary termination cases at ≪ 10 gestational weeks (n=10) (normal pregnancy group). Tissue samples were collected from each group by dilation and curettage under mask anesthesia. For all tissue samples, furin, TNF-α, and TGF-β2 primary antibodies were performed by immunohistochemical staining. The number of stained cells was evaluated by using the H-score technique. Results: In immunohistochemical examination, the immunoreactivities of furin, TNF-α, and TGF-β2 were found to be higher in syncytiotrophoblastic cells in the missed abortion group than in the normal pregnancy group (p<0.005). Additionally, high immunoreactivity of TNF-α and TGF-β2 molecules was established only in cytotrophoblastic cells of missed abortions (p<0.005) in examination at decidual cells of the missed abortion group; furin immunoreactivities were detected higher in the missed abortion group than in the control group, but TNF-α and TGF-β2 immunoreactivity were increased in number in the normal pregnancy group (p<0.005). Conclusion: It is considered that high levels of furin and the 2 furin-related proteins (TNF-α and TGF-β2), which play important roles in proliferation, invasion, migration, differentiation, and survival of cells, may be the reason of proceeding decidualization, placentation, and prevention from abortion, in spite of terminating the fetal life. © Science Printers and Publishers, Inc.Item Immune and inflammatory role of hydroxyethyl starch 130/0.4 and fluid gelatin in patients undergoing coronary surgery(Academic Press, 2015) Öztürk T.; Onur E.; Cerrahoğlu M.; Çalgan M.; Nizamoglu F.; Çivi M.Objectives: Compare the effects on inflammatory (TNF-α, IL-6, IL-8 and IL-10) and immunologic (CD3+, CD4+, CD8+, CD11b+, CD16+/56+ T cells and total lymphocyte concentration) variables of hydroxyethyl starch 130/0.4, 4% modified fluid gelatin, or crystalloid when used as volume replacement fluids for acute normovolemic hemodilution (a blood conservation technique) in coronary artery bypass graft patients. Methods: Thirty patients undergoing coronary artery bypass graft surgery were randomized to receive Isolyte S® (Group ISO), 6% hydroxyethyl starch 130/0.4 (Group HES) or 4% modified gelatin solution (Group GEL) for acute normovolemic hemodilution. Blood samples were taken immediately after induction of anaesthesia (T0), and 2h (T1), 12h (T2), 24h (T3), and 48h (T4) after separation from cardiopulmonary bypass. TNF-α, IL-6, IL-8 and IL-10 levels were determined with commercially available ELISA kits. CD3+ (mature T cells), CD4+ (T helper cells), CD8+ (suppressor cytotoxic T cells), CD16+/56+ (natural killer lymphocytes), and CD11b+ (Mac-1, adhesion receptor) levels were measured using flow-cytometry reagents. The CD4+:CD8+ ratio was calculated. Results: Between-group comparisons showed significantly higher levels of TNF-α at T1 (2h after weaning from cardiopulmonary bypass) in Group HES compared to Group ISO (p=0.003). IL-8 was significantly lower in Group HES than Group GEL at T1 (p=0.0005). IL-10 was significantly higher in Group HES than in Group GEL at T1 (p=0.0001). The CD4+:CD8+ ratio in Group ISO was significantly lower than that in Group HES at T2 (p=0.003). CD11b+ levels in Group HES were also higher than those in Group GEL and group ISO at T2, but not significantly. CD16/56+ levels in Group HES were higher than those in Group GEL at T2 (p<0.003). No excessive hemorrhage occurred in any patient. Mediastinal drainage during the first 24h after surgery in Group HES (347±207mL) was not significantly different from that of Group GEL (272±177mL) or Group ISO (247±109) (p>0.05). Conclusion: Hydroxyethyl starch 130/0.4 reduced pro-inflammatory responses and increased anti-inflammatory responses to a greater degree than gelatin solution and isolyte S®. The use of hydroxyethyl starch, compared to gelatin solution and isolyte S®, resulted in less decrease in the CD4+:CD8+ ratio, suggesting less immunosuppression. © 2014 Elsevier Ltd.Item Where does current and future pediatric asthma treatment stand? Remodeling and inflammation: Bird's eye view(John Wiley and Sons Inc., 2016) Yilmaz O.; Yuksel H.Airway remodeling is the chronic outcome of inflammation in asthma and a point of intervention between pediatric and adult ages. Pediatric asthma has been of great interest in the efforts to find a valuable time to interrupt remodeling. Various experimental and clinical research have assessed the effect of current therapeutic modalities on airway remodeling in asthma and many new agents are being developed with promising results. The heterogeneity in the results of these studies may lie in the heterogeneity of pathogenesis leading to asthma and remodeling; underlying the need for individualized treatment of the unique pathogenetic characteristics of each child's asthma. The aim of this review is to summarize the evidence about the influence of current and future therapeutic modalities in the concept of inflammation and remodeling in pediatric asthma. Pediatr Pulmonol. 2016;51:1422–1429. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.Item Immunomodulatory activities of alpha lipoic acid with a special focus on its efficacy in preventing miscarriage(Taylor and Francis Ltd, 2016) Monastra G.; De Grazia S.; Cilaker Micili S.; Goker A.; Unfer V.Introduction: Alpha lipoic acid (ALA) is an essential mitochondrial co-factor and, as a free molecule, it can exert multi-level immunomodulatory functions. Both ALA and its reduced form, dihydrolipoic acid (DHLA), are believed to be able to chelate heavy metals, to regenerate essential antioxidants and to repair important molecules damaged by oxidation. The largest part of the effects of ALA/DHLA couple can be explained by a specific stimulatory activity on Nrf2-dependent gene transcription and by the inhibition of NF-kB activity. These features have prompted its use as a drug for several diseases. Areas covered: This article surveys the main features of ALA/DHLA and its therapeutic effects. Its complex and differentiated function cannot simply be reduced to anti-inflammatory, antioxidant and detoxifying action. We highlight its capability to finely modulate several physiological pathways when unbalanced. In particular, we focus our attention on pregnancy, in relation to ALA administration by oral route and by a new formulation for vaginal delivery, in patients with threatened miscarriage. Expert opinion: Future efforts should be devoted to explaining carefully ALA/DHLA mechanism of action to reactivate the physiological balance when modified during pregnancy. On the other hand, ALA safety in pregnant women and its pharmacokinetics by vaginal route, have to be studied in depth. Moreover, ALA efficacy has to be confirmed in a much larger sample of patients. © 2016 Informa UK Limited, trading as Taylor & Francis Group.Item Evaluation of the gingival inflammation in pregnancy and postpartum via 25-hydroxy-vitamin D3, prostaglandin E2 and TNF-α levels in saliva(Elsevier Ltd, 2016) Gümüş P.; Öztürk V.Ö.; Bozkurt E.; Emingil G.Background Physiological changes and immunological modifications occur during pregnancy. The clinical and biological features of periodontal infections are affected by pregnancy. The aim of the present study was to evaluate saliva levels of 25-hydroxy-vitamin D3 (25(OH)D3), prostaglandin E2 (PGE2) and TNF-alpha (TNF-α) in pregnancy, postpartum and non-pregnant controls. Methods Whole saliva samples together with full-mouth clinical periodontal recordings were obtained from 59 pregnant, 47 post partum and 70 systemically healthy non-pregnant women. Groups were also evaluated according to the periodontal health status. 25(OH)D3, PGE2 and TNF-α levels in the saliva samples were determined by enzyme-linked immunoassays. Data were statistically tested by nonparametrical tests. Results Saliva TNF-α and PGE2 levels were significantly lower and 25(OH)D3 levels were significantly higher in the pregnant group than postpartum group (p < 0.0001). Saliva TNF-α and 25(OH)D3 levels were significantly higher and PGE2 levels were significantly lower in the control group than postpartum group (p < 0.0001). In the pregnant healthy, gingivitis and periodontitis groups saliva TNF-α levels were significantly lower than postpartum and control counterparts (p < 0.0001, p = 0.032, p = 0.003 and p = 0.013; p = 0.027; p = 0.007, respectively). In control healthy, gingivitis and periodontitis groups saliva 25(OH)D3 levels were significantly higher than the postpartum counterparts (p < 0.0001, p < 0.0001, p = 0.002, respectively). In the control healthy and gingivitis groups saliva 25(OH)D3 levels were significantly higher than pregnant healthy and gingivitis (p < 0.0001). Conclusions In conclusion, within the limits of the present study it seems that pregnancy have an effect on parameters in saliva in relation to the periodontal status of the women. Further studies are required for better understanding of the impact of periodontal diseases on pregnancy or otherwise. © 2015 Elsevier Ltd. All rights reserved.Item The association of HLA-G and immune markers in recurrent miscarriages(Taylor and Francis Ltd, 2016) Eskicioğlu F.; Özdemir A.T.; Özdemir R.B.; Turan G.A.; Akan Z.; Hasdemir S.P.Objective: To determine role of human leukocyte antigen (HLA)-G, CD8, CD16, CD56, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α for recurrent miscarriages in feto–maternal interface. Method: Chorion and decidua samples were obtained from 11 women with unwanted pregnancies (healthy pregnancy, HP) and 10 women with missed abortion diagnosis after at least two pregnancy losses (recurrent miscarriage, RM). In addition, endometrial tissues were obtained from 10 non-pregnant women (NonP). The expressions of markers were evaluated using the Western blot analysis. The values obtained between different groups were compared. Results: The highest protein expression of CD56 was found in the HP compared to NonP and RM. Meanwhile, the lowest protein expression of CD16 was observed in the NonP compared to HP and RM. The HLA-G expression exhibited the highest level in HP; however, there was no statistically significant difference between groups. CD8 and IFNγ expressions were lowest in the NonP group; however, TNF-α was highest in the RM group. Conclusions: The CD56 expression of uterine NK cells may be an indicator of a HP. However, not statistically significant, the increased expression of CD16, CD8, and also significantly increased expression of TNF may be associated with the predominant cytotoxic activity in the maternal immune system in patients with RM. Although there was no change in the expression of HLA-G, this finding may mean that the maternal immune system is unresponsive to HLA-G-mediated immunosuppressive signals originating from the fetus in these cases. © 2015 Taylor & Francis.Item Effects of two different eight-week walking programs on insulin resistance and ER stressrelated markers in pre-menopausal women; [Premenopozal kadınlarda 8 haftalık farklı şiddetteki yürüyüş antrenmanlarının insülin direnci ve ER stresiyle ilişkili markerler üzerine etkileri](Turkish Biochemistry Society, 2016) Doğru Y.; Büyükyazı G.; Ulman C.; Taneli F.; Tıkız H.; Göral M.; Esen H.Objective: The relationship between exercise and endoplasmic reticulum (ER) stress, insulin resistance, and obesity is a new field of research. To our knowledge, there are no studies examining the effects of walking exercises on ER stress related markers and insulin resistance in pre-menopausal women. To examine the effect of two different eight-week walking programs on the tumor necrosis factor-alpha (TNF-α), Fetuin-A (α2 - Heremans Schmid glycoprotein), c-Jun N-terminal kinase-1 (JNK-1) and retinol- binding protein-4 (RBP-4), the related markers of ER stress and insulin resistance in pre-menopausal women. Methods: Exercise groups (moderate tempo walking group; MTWG; n=11; brisk walking group BWG; n=12) walked five days a week, starting from 30 minutes, gradually increasing up to 51 minutes. BWG walked at ~70–75% and MTWG at ~50–55 of HRRmax. Body mass index (BMI), body fat percentage (%), VO2max, serum TNF-α, Fetuin-A, JNK-1, RPB-4, blood lipids, and insulin resistance levels were determined before and after the intervention. Results: VO2max increased in both exercise groups favoring BWG; RBP-4 decreased in both exercise groups (p<0.05). Serum TNF-α and, TG (p<0.05), BMI and percent body fat (p<0.01), and insulin levels reduced significantly in BWG (p<0.05). The reductions observed in both exercise groups in insulin resistance, and the increases determined in the negative levels of JNK-1 in BWG may be clinically important. Conclusion: Both type of walking resulted in similar positive effects on RBP-4. The reduction observed in TNF-α, RBP-4, and the increases in the negative levels of JNK-1 in BWG show the positive effects of brisk walking on ER stress. The reduction in insulin resistance in relation to the possible reductions in ER stress and apoptosis in BWG may be more effective to prevent metabolic diseases. © 2016, Turkish Biochemistry Society. All rights reserved.Item Gingival crevicular fluid and salivary resistin and tumor necrosis factor-alpha levels in Obese children with gingivitis(Wiley-Blackwell, 2018) Doğusal G.; Afacan B.; Bozkurt E.; Sönmez I.Background: This study aimed to evaluate the levels of resistin and tumor necrosis factor-alpha (TNF-α) in gingival crevicular fluid (GCF) and saliva of obese children with gingivitis. Methods: One-hundred and thirty children (65 obese and 65 normal weight; age range 8 to 12 years) were recruited for the study. The children were classified into four subgroups based on their body mass and periodontal status; 1) obese children with gingivitis (OG, n = 33); 2) obese children with healthy periodontium (OH, n = 32); 3) normal weight children with gingivitis (NWG, n = 32); 4) normal weight children with healthy periodontium (NWH, n = 33). Body mass index (BMI) percentile, probing pocket depth (PPD), gingival index (GI), and plaque index (PI) were recorded. Resistin and TNF-α were analyzed in GCF and saliva samples by ELISA. Results: Obese children had higher BMI percentiles than normal weight children (p < 0.0001). PPD, GI, PI, GCF volume, GCF, and salivary resistin and TNF-α levels were similar between obese and normal weight children (P > 0.05). OG and NWG subgroups had significantly higher GI, PI, GCF volume, GCF resistin total amounts, and salivary resistin concentrations but lower GCF resistin and TNF-α concentrations than OH and NWH (P < 0.0001 for all). GCF resistin total amounts were positively correlated with GI, PI, and GCF TNF-α total amounts (P < 0.05). Conclusions: To our knowledge, this is the first study evaluated the levels of resistin in GCF and saliva of children. Obesity is not associated with GCF and salivary resistin and TNF-α levels in children in the presence of gingival inflammation. © 2018 American Academy of Periodontology.Item Allergic rhinitis and its relationship with IL-10, IL-17, TGF-β, IFN-γ, IL 22, and IL-35(Hindawi Limited, 2018) Degirmenci P.B.; Aksun S.; Altin Z.; Bilgir F.; Arslan I.B.; Colak H.; Ural B.; Kahraman D.S.; Diniz G.; Ozdemir B.; Kırmaz C.Background. We aimed in our study to research the role of new cytokines such as IL-35, IL-22, and IL-17 that may form a target for novel treatment approaches. Methods. IL-10, IL-17, TGF-β, IFN-γ, IL-22, and IL-35 serum levels of allergic rhinitis (AR) patients were measured using ELISA method. Allergic sensitization was demonstrated by the skin prick test. Patients only with olive tree sensitivity were evaluated for seasonal AR (SAR). Patients only with mite sensitivity were included in the study for perennial AR (PAR). AR clinic severity was demonstrated by the nasal symptom scores (NSS). Results. In total, 65 AR patients (patient group), having 31 PAR and 34 SAR patients, and 31 healthy individuals (control group) participated in the study. Cytokine levels between the patient group and the control group were compared; IL-17 (p = 0 038), IL-22 (p = 0 001), and TGF-β (p = 0 031) were detected as high in the patient group, and IFN-γ (p < 0 001) was detected as low in the patient group. When correlation analysis was made between age, gender, prick test result, NSS, AR duration, and cytokine levels in the patient group, a negative correlation was detected only between IFN-γ (p = 0 032/r = −0 266) level and NSS. Conclusions. Accompanied by the literature information, these results made us think that T cell subgroups and cytokines have an important role in AR immunopathogenesis. It is thought that future studies to be conducted relating to this subject will form new targets in treatment. Copyright © 2018 P. Bayrak Degirmenci et al.Item Management of psoriatic arthritis: Turkish League Against Rheumatism (TLAR) expert opinions(Turkish League Against Rheumatism (TLAR), 2018) Nas K.; Kiliç E.; Çevik R.; Bodur H.; Ataman Ş.; Ayhan F.; Akgül Ö.; Akinci A.; Altay Z.; Çapkın E.; Dağli A.Z.; Duruöz T.; Gürer G.; Göğüş F.; Garip Y.; Kaçar C.; Kamanli A.; Kaptanoğlu E.; Kaya T.; Kocabaş H.; Özdemirel E.A.; Özel S.; Sezer İ.; Sunar İ.; Yilmaz G.Objectives: This study aims to establish the first national treatment recommendations by the Turkish League Against Rheumatism (TLAR) for psoriatic arthritis (PsA) based on the current evidence. Materials and methods: A systematic literature review was performed regarding the management of PsA. The TLAR expert committee consisted of 13 rheumatologists and 12 physical medicine and rehabilitation specialists experienced in the treatment and care of patients with PsA from 22 centers. The TLAR recommendations were built on those of European League Against Rheumatism (EULAR) 2015. Levels of evidence and agreement were determined. Results: Recommendations included five overarching principles and 13 recommendations covering therapies for PsA, particularly focusing on musculoskeletal involvement. Level of agreement was greater than eight for each item. Conclusion: This is the first paper that summarizes the recommendations of TLAR as regards the treatment of PsA. We believe that this paper provides Turkish physicians dealing with PsA patients a practical guide in their routine clinical practice. © 2018 Turkish League Against Rheumatism. All rights reserved.Item Comparison of some plasma inflammation markers in elite master athletes, recreational athletes and sedentary males; [Elit Master Atletler, Rekreasyonal Atletler ve Sedanter Erkeklerde Bazı Plazma İnflamasyon Markerlerinin Karşilaştinlmasi](Turkiye Klinikleri, 2019) Gİrgİner F.; Büyükyazi G.; Ulman C.; Doğru Y.; Taneli F.; Yildiz R.; Taş M.; Keskİnoğlu P.Objective: It is known that high-intensity exercises lead to muscle damage and fibrosis. This study aims to compare some plasma inflammation markers in elite master athletes, recreational athletes and sedentary males to determine muscle injury. Material and Methods: 60 healthy male participants (min-max 45-65 years) were divided into 3 groups: Elite master athletes performing high intensity training (EMAG; n=22), recreational athletes performing moderate intensity training (RG; n=21) and sedentary controls (CG; n=17). Resting serum levels of the monocyte chemoattractant protein-1 (MCP-1), High-Sensitivity C-Reactive Protein (hsCRP), Tumor Necrosis Factor Alfa (TNF-α), Transforming Growth Factor Beta-1 (TGF-β-1), and Klotho hormone were compared among the groups. Results: Body weight, fat percentages, body mass index were lower and MaxVO2 was higher in EMAG than those of both RG and CG. TGF-β-1 and Klotho Hormone levels of EMAG and RG were higher than CG. Vitamin D levels of EMAG were found higher than those of CG. Conclusion: Regular long-term endurance training has a long-term positive impact on the regeneration of muscle damage and inflammation. The high levels of Klotho hormone determined in EMAG provides a longer and healthier life by extending the initiation process of many illnesses including metabolic diseases. © 2019 by Türkiye Klinikleri.Item Gingival crevicular fluid and salivary HIF-1α, VEGF, and TNF-α levels in periodontal health and disease(Wiley-Blackwell, 2019) Afacan B.; Öztürk V.Ö.; Paşalı Ç.; Bozkurt E.; Köse T.; Emingil G.Background: Hypoxia-inducible factor-1 alpha (HIF-1α) is expressed as an adaptive response to hypoxia, mediates angiogenesis through the expression of vascular endothelial growth factor (VEGF) and can be induced by tumor necrosis factor-alpha (TNF-α). This study aimed to investigate the gingival crevicular fluid (GCF) and salivary HIF-1α, VEGF, and TNF-α levels in periodontal health and disease. Methods: A total of 87 individuals, 20 generalized aggressive periodontitis (G-AgP), 20 chronic periodontitis (CP), 26 gingivitis patients, and 21 periodontally healthy individuals, were included. Clinical periodontal parameters were recorded; GCF and salivary samples were collected; and HIF-1α, VEGF, and TNF-α levels were measured by enzyme-linked immunosorbent assay. Nonparametric tests were used for the statistical analyses. Results: G-AgP and CP groups had significantly higher GCF HIF-1α, VEGF, and TNF-α total amounts than gingivitis and healthy groups (P < 0.05). GCF HIF-1α and TNF-α total amounts in gingivitis group were significantly higher than the healthy group (P < 0.05). GCF and salivary concentrations of biomarkers were similar in both periodontitis groups (P > 0.05). Salivary HIF-1α concentrations in gingivitis group were significantly higher than G-AgP and healthy groups (P < 0.05). GCF HIF-1α, VEGF, and TNF-α total amounts were positively correlated with the site-specific clinical periodontal parameters and with each other (P < 0.05). Conclusions: HIF-1α is detectable in GCF and saliva of periodontally diseased and healthy individuals, and the GCF levels of the biomarker can be affected by disease status. Increased GCF HIF-1α, VEGF, and TNF-α levels in both chronic and aggressive form of periodontitis might suggest the role of TNF-α/HIF-1α/VEGF pathway in the pathogenesis of periodontal diseases. © 2018 American Academy of PeriodontologyItem Evaluation of xenon, light-emitting diode (LED) and halogen light toxicity on cultured retinal pigment epithelial cells(Taylor and Francis Ltd, 2019) Sezer T.; Altinisik M.; Guler E.M.; Kocyigit A.; Ozdemir H.; Koytak A.Objective: To compare the possible toxic effects of three light sources used in vitreoretinal endoillumination systems; halogen, xenon, and light-emitting diode (LED) on retinal pigment epithelium (RPE) cell cultures, after two different exposure times. Material and methods: ARPE-19 human RPE cell cultures were exposed to halogen, xenon, and LED light sources at a distance of 1.5 cm for 30 and 60 min with equal lumen output levels. Cells in the control group were not exposed. RPE cell cultures were compared in terms of cell viability, DNA damage, apoptosis rate, and IL-1ß, IL-6, and TNF- α levels. Results: The halogen light group showed significantly more DNA damage, higher TNF-α, IL-1β, and IL-6 levels, and lower viable cell count at 30 min compared to the control group. The rates of early and late apoptosis were also significantly higher at 60 min. There were no statistically significant differences in any of the parameters between the xenon and LED light sources and the control group at 30 or 60 min. Conclusion: New generation lights, xenon, and LED, seem to be safe in terms of RPE cells. Halogen light may cause toxic effects on RPE cells when used for a long time with maximal power output. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.Item Cytokine expression profiles in Autism spectrum disorder: A multi-center study from Turkey(Academic Press, 2020) Kutuk M.O.; Tufan E.; Gokcen C.; Kilicaslan F.; Karadag M.; Mutluer T.; Yektas C.; Coban N.; Kandemir H.; Buber A.; Coskun S.; Acikbas U.; Guler G.; Topal Z.; Celik F.; Altintas E.; Giray A.; Aka Y.; Kutuk O.Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in communication and social interaction as well as restricted interests and repetitive behaviors. The pathogenesis of ASD is not completely understood, but a growing body of research has demonstrated that the immune response may be a contributing factor in the etiology and/ or ontogeny of ASD. The aim of this study was to determine the expression levels of IL-1β, IL-1α, IL-4, IL-6, IL-17, TNF-α and TGF-β in peripheral blood mononuclear cells of children with ASD and healthy controls in order to determine the contributions of cytokines to ASD. Within the study timeframe, 195 children with ASDs (80.5% male) and 162 controls (73.6% male) were enrolled. Most children with ASD had a comorbid disorder (n = 114, 58.5%), with the most common diagnoses as Intellectual Developmental Disorder (IDD, n = 64, 32.8%) and ADHD (n = 64, 32.8%). The majority of children with ASD had severe autistic symptoms as evaluated via Childhood Autism Rating Scale (CARS, n = 130, 64.6%). The mean CARS score in the ASD sample was 40.8 (S.D. = 7.6). The patients with ASD were found to have significantly higher levels of IL-6 (p < 0.001) and significantly lower levels of IL-17 (p < 0.05, all Bonferroni corrected). Treatment tended to affect IL-4 levels. Lastly, discriminant function analysis (DFA) revealed that a combination of IL-6, IL-17 and IL-1α correctly classified 56.6% of cases. Despite extensive immunological evidence suggesting immune system aberrations, further research is required to clarify the relationship between immune profiles and ASD symptoms. © 2020 Elsevier LtdItem Novel inflammatory targets for immunotherapies in pediatric patients with trichotillomania(Elsevier GmbH, 2020) Kutuk M.O.; Tufan A.E.; Kilicaslan F.; Mutluer T.; Gokcen C.; Karadag M.; Yektas C.; Kandemir H.; Buber A.; Guler Aksu G.; Topal Z.; Giray A.; Celik F.; Acikbas U.; Kutuk O.Immune dysregulation may be important in the etiology of obsessive-compulsive and related disordersandbody-focusedrepetitivebehaviors, such as Trichotillomania (TTM). The role of inflammation and inflammatory markers in TTM has received relatively little attention. This study was aimed to determine the expression levels of inflammatory markers (i.e. IL-1β, IL-1α, IL-4, IL-6, IL-17, TNF-α and TGF-β) in peripheral blood mononuclear cells of children with TTM and healthy controls and to evaluate their association with clinical variables. Seventy-seven patients with TTM and 107 healthy controls were enrolled in the study. Peripheral blood was collected in standardized conditions. The mean age of patients and controls did not differ significantly (10.8 ± 4.4 and 12.0 ± 3.2 years; respectively). The majority of patients with TTM and controls were females (n = 55, 71.4 % and n = 55, 51.4 %; respectively); with a greater preponderance of females among TTM. Patients with TTM had significantly elevated expression levels of TNF-α, IL-6 and IL-17 compared to controls. However, the expression level of IL-4 was significantly reduced in TTM patients compared to controls. Accordingly, we found a pro-inflammatory state in TTM and those findings may suggest novel treatment options for TTM and further, cross-disciplinary studies focusing on neuro- inflammation in TTM conducted on larger samples are needed. © 2020 Elsevier GmbHItem NF-ĸβ upregulates ADAMTS5 expression by direct binding after TNF-α treatment in OUMS-27 chondrosarcoma cell line(Springer, 2020) Gun Bilgic D.; Hatipoglu O.F.; Cigdem S.; Bilgic A.; Cora T.Inflammation caused-aggrecan degradation is a critical event in the pathogenesis of osteoarthritis (OA). The aggrecanases like a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) are assumed to be key players in the aggrecan destruction. To develop the comprehensive therapy method for OA, it is essential to elucidate the activation mechanism of ADAMTS5 gene after stimulation of inflammatory cytokines like tumor necrosis factor-α (TNF-α). The cell lines of human chondrosarcoma (OUMS-27) and embryonic kidney (HEK293T) were incubated with tumor necrosis factor-α (TNF-α) for certain time periods, and the expression level of ADAMTS5 was measured in both mRNA and protein levels. Tissue-specific ADAMTS5 activation was founded to be induced after TNF-α treatment. Then, the constructs for the promoter region of ADAMTS5 were prepared and luciferase assay was conducted to understand the involvement mechanism of nuclear factor-kappa beta (NF-ĸβ) in ADAMTS5 activation. It was demonstrated that NF-ĸβ induces the ADAMTS5 expression level by directly binding the promoter region of ADAMTS5. Although the TNF-α blocker is used for OA treatment, the development of a more comprehensive treatment strategy is an urgent need. Our experimental data contributes in terms of selecting NF-ĸβ as a target molecule. Up to date, NF-ĸβ has been proven to involve in the ADAMTS5 up-regulation after several pro-inflammatory cytokines stimulation. In conclusion, our findings make important contributions to the knowledge about the roles of NF-ĸβ in ADAMTS5 activation under inflammatory conditions. So, NF-ĸβ could be considered to be a potential target for OA treatment. © 2020, Springer Nature B.V.Item The Effect of Resveratrol and Quercetin on Epithelial-Mesenchymal Transition in Pancreatic Cancer Stem Cell(Routledge, 2020) Hoca M.; Becer E.; Kabadayı H.; Yücecan S.; Vatansever H.S.Resveratrol and quercetin are phytochemicals that are found in a variety of plants. The aim of this study was to investigate the effect of resveratrol and quercetin on epithelial-mesenchymal transition (EMT) of CD133+ and CD133− pancreatic cancer cells. Cancer stem cells (CD133+ cells) were obtained from the PANC-1 cells by the MiniMACS system. CD133+ and CD133− PANC-1 cells were treated with different concentrations (5, 10, 25, 50, and 100 µM) of resveratrol and quercetin. Cell growth and cytotoxicity were evaluated by MTT assay. Anticancer and anti-metastatic properties of resveratrol and quercetin were determined by immunocytochemistry using antibodies (ACTA-2, IL-1β, N-cadherin, TNF-α, and vimentin). The immunostaining intensity of CD133+ cells was stronger than CD133− cells. ACTA-2, IL-1β, and N-cadherin immunoreactivities were significantly decreased, whereas TNF-α and vimentin immunoreactivities significantly increased in quercetin-treated CD133+ cells. Moreover, N-cadherin and TNF-α immunoreactivities significantly decreased in resveratrol-treated CD133+ cells. The reduction in N-cadherin and ACTA-2 immunoreactivities was higher than the increase in vimentin immunoreactivity, quercetin could prevent EMT to a greater extent than resveratrol in pancreatic cancer stem cells because of the reduced expression of N-cadherin. Quercetin could be more effective in inhibiting metastasis compared to resveratrol. © 2020, © 2019 Taylor & Francis Group, LLC.Item Effect of non-surgical periodontal treatment on gingival crevicular fluid hypoxia inducible factor-1 alpha, vascular endothelial growth factor and tumor necrosis factor-alpha levels in generalized aggressive periodontitis patients(Wiley-Blackwell, 2020) Afacan B.; Keleş Yücel Z.P.; Paşali Ç.; Atmaca İlhan H.; Köse T.; Emingil G.Background: Hypoxia-inducible angiogenic pathway involving hypoxia inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF-α) may regulate several biological processes related to inflammation. The present study aimed to assess the effect of non-surgical periodontal treatment on gingival crevicular fluid (GCF) HIF-1α, VEGF, and TNF-α levels in generalized aggressive periodontitis (G-AgP). Methods: Twenty G-AgP patients and 20 periodontally healthy individuals were included. G-AgP patients received scaling and root planning (SRP), per quadrant at a 1-week-interval, performed with ultrasonic and periodontal hand instruments. GCF samples were collected and clinical periodontal parameters including probing depth, clinical attachment level, gingival index and plaque index were recorded at baseline, 1 and 3 months after treatment. Biomarker levels in GCF were analyzed by ELISA. Results: At baseline all clinical parameters and GCF HIF-1α, VEGF, and TNF-α levels were significantly higher in G-AgP patients compared to healthy control (P < 0.05). All clinical parameters improved over the 3-month-period in G-AgP patients (P < 0.05). GCF HIF-1α levels in G-AgP reduced at 1 and 3 months post-treatment, however, this did not reach to statistical significance (P > 0.05). GCF VEGF and TNF-α levels remained unchanged throughout the study period (P > 0.05). Conclusions: Within the limitations of the present study, although HIF-1α seems to possess a potential diagnostic value for G-AgP, it might not be a proper predictor of clinically favorable treatment outcome. SRP plus different adjunctive therapies could provide better information about the prognostic role of hypoxia-inducible angiogenic pathway in G-AgP. © 2020 The Authors. Journal of Periodontology published by Wiley Periodicals, Inc. on behalf of American Academy of PeriodontologyItem In-vitro evaluation of effects of mesenchymal stem cells on tlr3, tlr7/8 and tlr9-activated natural killer cells(Kare Publishing, 2021) Ozdemir A.T.; Kirmaz C.; Ozdemir R.B.O.; Degirmenci P.; Oztatlici M.; Degirmenci M.Objectives: In this study, it was aimed to investigate the immunomodulatory effects of Mesenchymal stem cells (MSCs) on Natural Killer (NK) cells activated by Toll-like receptor (TLR) agonists. Methods: MDA-MB-231, MCF-7 and NK-92 cells were induced with TLR3, TLR7/8 and TLR9 agonists and co-cultured with MSCs. Alterations in IFN-γ, TNF-α, Granzyme-b and Perforin expressions were determined by qPCR method, CD69 and CD107a expressions were determined by flow cytometry, and cytotoxicity was determined by MTT-assay. Results: All TLR agonists significantly increased the expressions of the IFN-γ, TNF-α, Granzyme-b, Perforin, CD69 and CD107a in-vitro. We determined that the cytokine, cytotoxic molecules, and activation markers of NK-92 cells interact-ing with breast tumor cells significantly increased by TLR3 and TLR9 agonists. However, suppression rather than activation occurred on the NK-92 cells due to the simultaneous induction of the immunosuppressive effects of MSCs by these agonists. On the other hand, the TLR7/8 agonists provided a low NK-92 induction, however, the inhibitory effects of MSCs were not triggered. Therefore, it provided a more significant activation than TLR3 and TLR9 agonists. Conclusion: Our findings suggested that TLR7/8 agonists may be a better choice to induce antitumor effects of NK cells in a tumor tissue rich in MSCs. © 2021 by Eurasian Journal of Medicine and Oncology.