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Article Citation - WoS: 1Citation - Scopus: 2Cannabinoid Receptor Ligands Modulate Fibrosis and Inflammation in Idiopathic Pulmonary Fibrosis: a Preliminary Study(Tubitak Scientific & Technological Research Council Turkey, 2024) Kose, Sevil; Onen, Selin; Gizer, Merve; Boduroglu, Esin; Gonullu, Ugur; Korkusuz, PetekBackground/aim: No specific pharmacological treatment regimen for idiopathic pulmonary fibrosis (IPF) exists. Therefore, new antiinflammatory therapeutic strategies are needed. Cannabinoids (CBs), known for their inflammation-modulating and antifibrotic effects, may be potential medication candidates for treating IPF. We aim to evaluate the inflammation-modulating and antifibrotic effects of CB receptor (CBR) agonists and antagonists in lipopolysaccharide-stimulated normal human lung fibroblast, epithelial cells, IPF fibroblast cells, and monocytes. Materials and methods: We detected CBRs in normal human lung fibroblasts (LL24) and IPF fibroblast cells (LL29), epithelial cells (A549) and monocytes (THP-1) by flow cytometry. We determined TGF-(31, IL-8, and TNF-alpha inflammatory cytokines in the LL24, LL29, A549, and THP-1 cell culture supernatants on days 1 and 5 by ELISA. We evaluated the cell viability in LL24, LL29, and A549 cells on days 1, 3, and 5 spectrophotometrically and detected collagen Type I (ColI) production in the LL24 and LL29 cell culture supernatants on days 1, 3, and 5 by ELISA. Results: LL24, LL29, A549, and THP-1 cells exhibited CB1 (CB1R) and CB2 (CB2R) receptors. CB1R and CB2R agonists WIN55,2122 and JWH015 inhibited fibroblastic and epithelial cell proliferation on day 5. TGF-(31 and TNF-alpha release increased, while IL-8 release decreased in LL24, LL29, A549, and THP-1 cells in response to the administration of WIN55,212-2 and JWH015 at a 10-2 mM concentration. CB1R and CB2R antagonists AM251 and AM630 did not block agonistic responses, suggesting a nonclassical CBRmediated pathway. CB2R agonist JWH015 decreased ColI expression in IPF lung fibroblasts LL29 on day 3. Conclusion: These results suggest that CB signaling regulates the progression of pulmonary inflammation and fibrosis via CBR activation. This may offer a potential pharmacological tool for developing antifibrosis therapies.Article Citation - WoS: 6Citation - Scopus: 6Quantitative Lipidomic Analysis of Takotsubo Syndrome Patients' Serum(Frontiers Media Sa, 2022) Karnati, Srikanth; Guntas, Gulcan; Rajendran, Ranjithkumar; Shityakov, Sergey; Hoering, Marcus; Liebisch, Gerhard; Foerster, Carola Y.Takotsubo syndrome (TTS), also known as the transient left ventricular apical ballooning syndrome, is in contemporary times known as novel acute cardiac syndrome. It is characterized by transient left ventricular apical akinesis and hyperkinesis of the basal left ventricular portions. Although the precise etiology of TTS is unknown, events like the sudden release of stress hormones, such as the catecholamines and the increased inflammatory status might be plausible causes leading to the cardiovascular pathologies. Recent studies have highlighted that an imbalance in lipid accumulation might promote a deviant immune response as observed in TTS. However, there is no information on comprehensive profiling of serum lipids of TTS patients. Therefore, we investigated a detailed quantitative lipid analysis of TTS patients using ES-MSI. Our results showed significant differences in the majority of lipid species composition in the TTS patients compared to the control group. Furthermore, the computational analyses presented was able to link the altered lipids to the pro-inflammatory cytokines and disseminate possible mechanistic pathways involving TNF alpha and IL-6. Taken together, our study provides an extensive quantitative lipidome of TTS patients, which may provide a valuable Pre-diagnostic tool. This would facilitate the elucidation of the underlying mechanisms of the disease and to prevent the development of TTS in the future.Article Citation - WoS: 2Citation - Scopus: 2Protective Effect of Aerobic Exercise on the Nasal Mucosa of Rats Against the Histopathologic Changes in Cigarette Smoke Exposure(Sage Publications inc, 2020) Akkoca, Ozlem; Unlu, Ceren Ersoz; Tatar, Ilkan; Sargon, Mustafa Fevzi; Zeybek, Dilara; Oguztuzun, SerpilIntroduction: Smoking is a public health problem that has been proven to have adverse effects on human health. Aerobic exercise has positive effects on the human body, especially on the respiratory system. Objective: The aim of this experimental animal model study was to determine whether regular aerobic exercise has a protective effect against the harmful effects of cigarette smoke on the nasal mucosa of rats. Methods: A total of 24 male Wistar albino rats were randomly separated into 3 groups of 8: group 1 (cigarette smoking), group 2 (cigarette smoking and exercise), and group 3 (control group). At the end of the experiment period, histopathological (light and electron microscopy) and immunohistochemical (GSTA 1, CYP1A1, and CYP2E1) evaluations were made of the nasal mucosa of the animals. Results: Goblet cell loss and basal membrane thickening were significantly lower in group 2 and group 3 compared to group 1. In the electron microscope evaluation, the inflammatory expressions of the goblet cells were observed in a very small area in group 2. In group 1, these were distributed over large areas between the mucosal cells. There was seen to be significant swelling of the mitochondria in group 1 compared to the other groups. No statistically significant difference was determined between the groups with respect to GSTA1, CYP2E1, and CYP1A1 scores (P> .05). Conclusion: The results of this study showed that regular aerobic exercise has a protective effect against the harmful effects of smoking on the nasal mucosa of rats.Article Citation - WoS: 1Citation - Scopus: 1Is increased activator protein 1 in cerebrospinal fluid as a potential biomarker that distinguishes idiopathic intracranial from sclerosis?(Aepress Sro, 2024) Karabork, Seyda; Celik, Humeyra; Dursun, Ali Dogan; Ankarali, Handan; Turkoglu, Sule AydinOBJECTIVES: To distinguish whether idiopathic intracranial hypertension (IIH) is a condition predisposing to multiple sclerosis (MS) or an isolated disease, the current gene transcription factor Activator Protein -1 (AP -1) was evaluated with its potential to differentiate both diseases. BACKGROUND: The aim of this study was to investigate the use of AP -1 as biomarkers for the discrimination of IIH and MS. METHODS: AP -1, TNF-alpha, and IL -6 protein values in the CSF of the cases were evaluated by the ELISA method. The numerical measures of the groups and the ability of AP -1 to distinguish the groups were analyzed with the ROC curve. RESULTS: There was no difference between the groups in CSF TNF-alpha, IL -6, CSF, and serum biochemistry analyses. However, it was determined that the AP -1 concentration (pg/ml) was significantly higher in the IIH group, the sensitivity of AP -1 in separating those with IIH was 75%, and the specificity in separating those with MS was 60% in those with an AP -1 concentration of 606.5 and above. CONCLUSION: According to our results, the fact that CSF TNF-alpha and IL -6 values did not differ in IIH compared to MS revealed that IIH could not methodologically control MS, and AP -1 was a supportive parameter in differentiating both diseases (Tab. 2, Fig. 1, Ref. 31) . Text in PDF www.elis.skArticle Citation - WoS: 4Citation - Scopus: 4Neuroprotective effects of adrenomedullin in experimental traumatic brain injury model in rats(Turkish Assoc Trauma Emergency Surgery, 2022) Emmez, Gokcen; Bulduk, Erkut Baha; Yildirim, ZuhalBACKGROUND: Traumatic brain injuries cause damages in the brain in several ways, which include cell death because of edema, disruption of the blood-brain barrier, shear stress, and ischemia. In this study, we investigated the effects of adrenomedullin (AM) on oxidative stress and inflammation after head traumas in a rat model. METHODS: Eighteen male adult Wistar albino rats were randomized into three groups (n=6). No traumas were applied to the control (C) group. Traumas were applied in line with Marmarau trauma model in the trauma group. The rats in the AM treatment group were treated with post-traumatic 12 mu g/kg i.p. AM in addition to the trauma group. The rats were followed for 7 days in all groups and were then sacrificed. Brain tissues and blood samples were taken. RESULTS: In the trauma group, both tissue and serum MDA, TNF-alpha, and IL-6 levels were significantly increased compared to the control group (p<0.05). In the AM-treated group, serum TNF-alpha levels were significantly decreased compared to the trauma group (p<0.05). In the trauma group, both tissue and serum GSH levels were significantly decreased compared to the control group (p<0.05). In the trauma group, serum Vitamin D3 levels were significantly decreased compared to the control group (p<0.05). In the AM-treated group, both tissue and serum GSH levels were significantly increased compared to the trauma group (p<0.05). CONCLUSION: These results indicate that AM has neuroprotective effects on traumatic brain injury in a rat model.Article Citation - WoS: 3Citation - Scopus: 4Anti-Inflammatory, Antioxidant, and Anti-Atherosclerotic Effects of Natural Supplements on Patients With Fmf-Related Aa Amyloidosis: a Non-Randomized 24-Week Open-Label Interventional Study(Mdpi, 2022) Romano, Micol; Garcia-Bournissen, Facundo; Piskin, David; Rodoplu, Ulkumen; Piskin, Lizzy; Elzagallaai, Abdelbaset A.; Demirkaya, ErkanWe aimed to evaluate the effect of a combination of natural products on parameters related to inflammation, endothelial dysfunction, and oxidative stress in a cohort of familial Mediterranean fever (FMF) patients with Serum Amyloid A amyloidosis, in a non-randomized, 24-week open-label interventional study. Morinda citrifolia (anti-atherosclerotic-AAL), omega-3 (anti-inflammatory-AIC), and extract with Alaskan blueberry (antioxidant-AOL) were given to patients with FMF-related biopsy-proven AA amyloidosis. Patients were >18 years and had proteinuria (>3500 mg/day) but a normal estimated glomerular filtration rate (eGFR). Arterial flow-mediated dilatation (FMD), carotid intima media thickness (CIMT), and serum biomarkers asymmetric dimethylarginine (ADMA), high sensitivity C-reactive protein (hs-CRP), pentraxin (PTX3), malondialdehyde (MDA), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), and glutathione peroxidase (GSH-Px) were studied at baseline and after 24 weeks of treatment. A total of 67 FMF-related amyloidosis patients (52 male (77.6%); median age 36 years (range 21-66)) were enrolled. At the end of a 24-week treatment period with AAL, AIC, and AOL combination therapy, ADMA, MDA, PTX3, hsCRP, cholesterol, and proteinuria were significantly decreased compared to baseline, while CuZn-SOD, GSH-Px, and FMD levels were significantly increased. Changes in inflammatory markers PTX3, and hsCRP were negatively correlated with FMD change, and positively correlated with decreases in proteinuria, ADMA, MDA, cholesterol, and CIMT. Treatment with AAL, AIC and AOL combination for 24 weeks were significantly associated with reduction in inflammatory markers, improved endothelial functions, and oxidative state. Efficient control of these three mechanisms can have long term cardiovascular and renal benefits for patients with AA amyloidosis.Article Citation - WoS: 2Citation - Scopus: 2Paraoxonase and Oxidative Stress Changes in Left and Right Ventricles of Exhaustively Exercised Rats(Canadian Science Publishing, 2021) Sarikaya, Badegul; Runa, Metin; Dayanir, Duygu; Gunduztepe, Yasemin; Pinar, LamiaExhaustive exercise can cause subclinical inflammation to the heart, as it is an oxidative tissue that works continuously. The effect of exhaustive exercise on left and right ventricles (LVs, RVs) may be different. It is claimed that paraoxonase-1 (PON1), an antioxidant enzyme, has a cardioprotective effect on oxidative stress. Rats were separated as non-exercised controls (Con), those euthanized immediately after (E-0) and 24 h after exhaustive exercise (E-24). Cardiac troponin-I (cTnI), total antioxidant status (TAS), total oxidant status (TOS), PON1 activities, and histological findings in LV and RV of the exhausted rats were evaluated. TAS and PON1 levels were lower in LVs compared with RVs of all groups. TOS levels were high in LVs compared with RVs of all groups. In LVs, TAS levels decreased significantly in the E-0 group while PON1 activity decreased in E-0 and E-24 groups compared with controls. In LVs, TOS levels decreased significantly in E-0 and E-24 groups, but in RVs a decrease was seen only in the E-0 group. cTnI levels increased significantly in the E-0 group and decreased to control levels in the E-24 group. Considering the histological and biochemical findings, exhaustive exercise affected the heart to the maximum during and just after exhaustion, and LV was influenced more than RV.Article Citation - WoS: 3Citation - Scopus: 5Subclinical Inflammation Is Associated With Reductions in Muscle Oxygenation, Exercise Capacity and Quality of Life in Adults With Type 2 Diabetes(Elsevier, 2020) Bozdemir-Ozel, Cemile; Arikan, Hulya; Calik-Kutukcu, Ebru; Karaduz, Beyza Nur; Inal-Ince, Deniz; Kabakci, Giray; Dagdelen, SelcukObjectives: Exercise capacity is related to both morbidity and mortality in patients with type 2 diabetes (T2DM). The aim of this study was to investigate the relationship between subclinical inflammation level, exercise capacity, muscle oxygenation and quality of life in T2DM. Methods: This study includes 28 patients with T2DM (mean age, 51.5 +/- 5.0 years; male-to-female ratio, 6:22). Exercise capacity was evaluated using an incremental symptom-limited maximal exercise test on a bicycle ergometer. Muscle oxygenation was investigated using a wearable lactate-measuring device. Diabetes-specific quality of life was assessed using the Diabetes Quality of Life Questionnaire (DQOL). Subclinical inflammation was assessed using C-reactive protein (CRP) levels. Results: CRPlevelwasnegatively correlatedwith peakworkload during the test (r=-0.588, p=0.002), muscle oxygenation (r=-0.465, p= 0.019) and the psychological impact of treatment subscale of the DQOL (r= e0.540, p=0.017), and positively correlated with body mass index (r=0.519, p=0.008), waist circumference (r=0.426, p=0.038) and fat percentage (r=0.573, p=0.004). Therewasnocorrelation betweenCRPand fasting blood glucose or glycated hemoglobin level (p>0.05). Peakworkloadwas inversely related to fat percentage (r=-0.467, p=0.016) and the DQOLworry about the future impact of diabetes subscale (r=-0.501, p=0.021). Conclusions: In our study, subclinical inflammation negatively affected muscle oxygenation, exercise capacity and quality of life independently of glycemic indicators. Our findings suggest that the degree of glycemic control is insufficient to explain lower exercise capacity. Further studies are needed to investigate subclinical inflammation-reducing interventions in T2DM. (C) 2020 Canadian Diabetes Association.
