Browsing by Author "Birlik, Merih"

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Citation - WoS: 6
Citation - Scopus: 5
Antioxidant Effect of Epigallocatechin-3 in a Bleomycin-Induced Scleroderma Model
(Turkish League Against Rheumatism, 2019) Kocak, Ayse; Harmancı, Duygu; Cavdar, Zahide; Ural, Cemre; Birlik, Merih; Sarioglu, Sulen; Yilmaz, Osman; Akdoğan, Gül
Objectives: This study aims to evaluate the antioxidant effects of epigallocatechin-3-gallate (EGCG) in a bleomycin (BLM)-induced scleroderma model. Materials and methods: Thirty-two healthy female Balb-c mice (6-8-week-old; weighing 22 +/- 5 g) were used in this study. The mice were randomly divided into four groups: control (n=8), BLM (n=8), BLM+EGCG (n=8), and EGCG (n=8). Skin tissue specimens were collected at the end of the experiments. Histopathological examinations of skin tissues were performed. Skin samples were assessed for total superoxide dismutase (SOD) activity and malondialdehyde (MDA) content. The phosphorylation of p-38 mitogen-activated protein kinase and Akt protein (the serine-threonine protein kinase encoded by the AKT), as well as the nuclear factor-kappa B (NF-kappa B) levels, were analyzed by western blotting. Results: Epigallocatechin-3-gallate-treated groups were observed to have reduced connective tissue fibrosis in the dermis area using Masson's trichrome staining method. Pp-38 and NF-kappa B were found to decrease significantly in the BLM + EGCG group compared with the BLM group. Parallel to these findings, phosphorylated Akt protein was found to increase in the BLM + EGCG group compared with the BLM group. SOD activity was increased in the EGCG group and content of MDA level was decreased in EGCG groups. Conclusion: The results of the present study demonstrated that EGCG represses pp-38 and NF-kappa B signaling pathways, exerting a protective effect for scleroderma through its anti-oxidative role.
Comparison of Pulmonary Function, Respiratory Symptoms, Functional Level, and Health-Related Quality of Life in Patients With Systemic Sclerosis According To Smoking Status
(Taylor & Francis Inc, 2022) Yakut, Hazal; Ozalevli, Sevgi; Aktan, Ridvan; Erez, Yesim; Birlik, Merih
Background Patients with systemic sclerosis (SSc) are at high risk for pulmonary and vascular complications. Smoking is an important risk factor for respiratory symptoms and vascular complications of many diseases in the general population. However, studies on the role of smoking in SSc are insufficient. Aims This study aimed to compare pulmonary function, respiratory symptoms, functional level, and health-related quality of life (HRQoL) in patients with SSc according to smoking status and to assess the correlation between cigarette consumption and these parameters in patients with SSc. Methods Seventy-two patients with SSc (smoker group; n = 35 or nonsmoker group; n = 37) were included. The pulmonary function test was measured with a spirometer. Respiratory symptoms were questioned and the perceived severity of dyspnea and fatigue was evaluated. The functional levels were determined by questioning the patients' average daily walking distance, exercise habits, and daily sedentary time. HRQoL was assessed by Scleroderma Health Assessment Questionnaire. Results The rate of respiratory symptoms including dyspnea, cough, and sputum were higher in the smoker group (p .001, p = .041, and p .001, respectively). Also, the perceived severity of dyspnea and fatigue was higher in the smoker group (p < .05). The mean daily walking distance, exercise habits, and overall HRQoL were lower (p = .004, p = .002, and p = .034, respectively) and the sedentary time and vascular complications were higher (p .001 and p = .038, respectively) in the smoker group. However, there was no significant difference between the two groups in terms of the pulmonary function test (p > .05). There was a weak to moderate correlation between cigarette consumption and respiratory symptoms, dyspnea and fatigue severity, functional level, and HRQoL in the smoker group (0.001 <= p <= .024). Conclusions Smoking may increase respiratory symptoms and vascular complications and decrease the functional level and HRQoL in patients with SSc. To maintain functional independence in patients with SSc, awareness of the harms of smoking should be increased and smoking cessation should be encouraged, along with physiotherapy and rehabilitation programs including exercise and physical activity recommendations.
Citation - WoS: 2
Citation - Scopus: 4
Effects of Epigallocatechin-3 (egcg) on a Scleroderma Model of Fibrosis
(Walter De Gruyter Gmbh, 2018) Kocak, Ayse; Harmancı, Duygu; Birlik, Merih; Sarioglu, Sulen; Yilmaz, Osman; Cavdar, Zahide; Akdoğan, Gül
Objective: The aim of the present study was to evaluate the potential protective effects of epigallocatechin-3-gallate (EGCG) on fibrosis in bleomycin induced scleroderma model. Materials and methods: Thirty-two healthy female Balb-c mice with the average body weight of 22 +/- 5 g were used in this study. The mice were randomly divided into four groups as control (n=8), Bleomycin (n=8), Bleomycin+ EGCG (n =8) and EGCG (n =8). Skin tissue samples were collected to quantify matrix metalloproteinases (MMP-1, MMP-8, MMP-13), p-SMAD 2/3 and SMAD 2/3 in protein homogenates by western blotting. TGF-beta 1 expression was determined by real-time PCR. Immunohistopathological and histopathological examinations of skin tissues were also done. Results: When measured with Masson Trichrome, EGCG treatment was found to decrease fibrosis in connective tissue compared to the BLM injected control. EGCG was decreased dermal fibrosis. Bleomycin + EGCG group showed a significant reduction in fibrosis at the dermal surface area using hematoxylin measurements compared with the BLM group. MMP-1, MMP-8 protein levels were increased and p-SMAD 2/3 protein level was decreased. TGF-beta mRNA expression was decreased in the EGCG + BLM group compared with the BLM group. Conclusion: These results suggest an antifibrotic role for EGCG.
Citation - WoS: 6
Citation - Scopus: 6
Relationship of Wnt Pathway Activity and Organ Involvement in Scleroderma Types
(Wiley, 2020) Kocak, Ayse; Harmancı, Duygu; Akdoğan, Gül; Birlik, Merih
Objective Scleroderma (SSc) is a chronic inflammatory autoimmune disease characterized by fibrosis in the skin and internal organs. In SSc, the heart, lung, kidney, gastrointestinal (GIS) system, muscle, and peri-articular structures are damaged. There is no study of the relationship between SSc type, stage, pathogenesis, organ involvement, and Wnt signaling. In this study, we aimed to show the relationship of the Wnt gene family and antagonists in SSc subtypes and different organ involvement. Methods Eighty-five SSc patients and 77 controls were included in this study. The gene expressions and protein levels of the Wnt family and antagonists were analyzed from blood samples. The relationship between these parameters and disease stage, type, and organ involvement were evaluated. Results Wnt-1, Wnt-10b, Wnt-2, and Wnt-6 gene expressions are increased and Axin-2, DKK-1, and Kremen protein expressions are decreased in SSc. Wnt-3a and Wnt-10a gene expressions are increased in generalized SSc compared to limited SSc. Wnt-1, Wnt-2 gene expressions are increased significantly in pulmonary arterial hypertension (PAH)(+) SSc compared to PAH(-) SSc. There was a positive correlation between the modified Rodnan skin score and Wnt-2 in SSc. There was a significant positive correlation between GIS involvement score and Wnt-1, Wnt-2, Wnt-4, Wnt-8a, Wnt-9b in SSc. Conclusion Wnt-1 and Wnt-2 were found higher in scleroderma and organ involvement. They may play a role in the pathogenesis of the disease.
Citation - WoS: 1
Citation - Scopus: 2
Selective JAK-1 Inhibitor Upadacitinib and Peptide PD29 Modulate the JAK and TGF-β/Smad Signaling Pathways Reducing Experimental Dermal Fibrosis
(Pergamon-elsevier Science Ltd, 2025) Kocak, Ayse; Ural, Cemre; Cavdar, Zahide; Sarioglu, Sulen; Akdogan, Gul; Birlik, Merih
This study investigates the antifibrotic and anti-inflammatory effects of Janus kinase (JAK) inhibitors and the PD29 peptide in the context of systemic sclerosis (SSc), a condition characterized by dermal thickening, chronic inflammation, and excessive extracellular matrix deposition. Pulmonary arterial hypertension (PAH) and pulmonary fibrosis represent serious and often fatal complications associated with SSc. The pathogenesis of SSc involves dysregulation of immune responses and aberrant activation of signaling pathways, including TGF beta/Smad. The antifibrotic properties of upadacitinib, a selective JAK1 inhibitor, and PD29 peptide were evaluated using a bleomycin-induced SSc mouse model and primary human lung fibroblasts. Both agents, administered individually or in combination, significantly attenuated dermal thickening, myofibroblast transdifferentiation, collagen deposition, and activation of the TGF-beta 1 signaling axis. In vivo and in vitro analyses demonstrated that upadacitinib and PD29 downregulated key fibrotic markers, including alpha-SMA, JAK1, TGF-beta 1, Smad2, and collagen-1, at both the gene and protein levels. Furthermore, treatment significantly reduced systemic inflammatory cytokines, including IL-6 and TNF-alpha. Notably, combination therapy exhibited a more pronounced effect compared to monotherapy. These findings suggest that upadacitinib and PD29 exert potent antifibrotic and anti-inflammatory effects through suppression of TGF-beta 1-mediated Smad2/3 signaling, predominantly via inhibition of JAK1 activation. Consequently, JAK inhibitors and PD29 represent promising therapeutic candidates for the management of fibrosis in systemic sclerosis.