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Öğe Anti-proliferative effects of beta-blocker propranolol on human lung cancer and noncancer cells(Aepress Sro, 2023) Terzi, Menderes Yusuf; Urhan-kucuk, MeralOBJECTIVE: Propranolol (PRO) has been recently discovered to possess anti-tumorigenic effects in cancer patients. So, we aimed to enlighten the in vitro effects of PRO in A549 lung cancer cells and BEAS2B nontumoral lung cells.METHODS: The gene expression levels of apoptotic proteins; caspases 3, 8, and 9 (CASP3, 8, 9), apoptosis inducing factor (AIF), and DNA damage inducible transcript 3 (DDIT3) and cell cycle regulatory proteins; WEE1 G2 checkpoint kinase (WEE1) and cyclin dependent kinase inhibitor 1A (CDKN1A) were analyzed with quantitative reverse-transcription PCR to assess the effect of PRO on A549 tumor and BEAS2B nontumoral cells. The protein levels of CASP3 and AIF1 were detected with Western blot.RESULTS: PRO exerted its anti-tumorigenic effects against A549 cells by arresting cell cycle via CDNK1A and by inducing apoptosis via caspase-dependent (CASP3) and -independent pathways (AIF, DDIT3). As to nontumoral BEAS2B cells, PRO decreased the cell viability at a lesser extent compared to tumoral cells. In contrast to tumor cells, PRO reduced the protein levels of CASP3 and AIF1. Notably, at 48th hour of PRO treatment, we observed a sustained expression of elevated DDIT3 mRNA levels at 24h in BEAS2B cells unlike in A549 cells.CONCLUSION: We suggest that D DIT3 and CDKN1A play a critical role during cell fate decision after PRO treatment by protecting nontumoral cells against apoptosis and by triggering apoptosis in tumor cells. The selective action mechanism of PRO with less cytotoxicity in nontumoral lung cells puts it forward as a promising adjuvant agent in lung cancer therapy (Tab. 1, Fig. 4, Ref. 50). Text in PDF www.elis.skÖğe Association of miR-21-5p with routine biochemical markers and inflammatory cytokines in hemodialysis patients(Elsevier, 2023) Okuyan, Hamza Malik; Terzi, Menderes Yusuf; Dogan, Serdar; Emir, Tuerkan; Turgut, Faruk HilmiBackground: Although the role of miR-21-5p in some kidney diseases is relatively documented, the relationship of miR-21-5p with markers of bone metabolism and inflammation in patients receiving hemodialysis (HD) remains unclear. Here, we aim to explore the relationship of miR-21-5p with routine biochemical parameters, mineral bone disorders, and inflammatory markers in HD patients. Methods: Serum miR-21-5p expressions from 60 HD patients and 20 healthy controls were analyzed with qPCR. Bone metabolism-related parameters such as receptor activator of nuclear factor-kappa B ligand (RANKL), osteocalcin, calcium, phosphorus, and parathormone; inflammation-related markers such as tumor necrosis factor-alpha (TNF-& alpha;), interleukin (IL)-6, IL-10, and C-reactive protein (CRP); and oxidative stress markers such as total antioxidant status (TAS) and total oxidant status (TOS) were measured in serum samples of HD patients. Results: We showed for the first time that miR-21-5p expressions were increased in patients receiving HD. In addition, miR-21-5p expressions showed a significantly positive correlation with bone metabolism markers, i.e. RANKL, osteocalcin, phosphorus, and parathormone, and inflammation markers, i.e. TNF-& alpha;, IL-6, and CRP. We detected that areas under the receiver operating characteristic curve for miR-21-5p, RANKL, osteocalcin, TNF-a, IL-6, and oxidative stress index in HD patients were 0.9317, 0.7742, 0.9038, 0.7319, 0.7063, and 0.7738, respectively. Conclusion: Elevated miR-21-5p expressions are associated with routine biochemical and inflammatory markers in HD patients, suggesting that miR-21-5p might have diagnostic and/or therapeutic importance in the treatment of chronic kidney diseases.Öğe Association of serum lncRNA H19 expression with inflammatory and oxidative stress markers and routine biochemical parameters in chronic kidney disease(Springer, 2021) Okuyan, Hamza Malik; Dogan, Serdar; Terzi, Menderes Yusuf; Begen, Mehmet A.; Turgut, Faruk HilmiBackground Chronic kidney disease (CKD) is a disorder that affects millions worldwide, and current treatment options aiming at inhibiting the progression of kidney damage are limited. Long noncoding RNA (lncRNA) H19 is one of the first explored lncRNAs and its deregulation is associated with renal pathologies, such as renal cell injury and nephrotic syndrome. However, there is still no research investigating the connection between serum lncRNA H19 expressions and clinical outcomes in CKD patients. Therefore, we investigated the relation of serum lncRNA H19 expressions with routine biochemical parameters, inflammatory cytokines, oxidative stress and mineralization markers in advanced CKD patients. Methods lncRNA H19 serum levels from 56 CKD patients and 20 healthy controls were analyzed with reverse-transcription quantitative polymerase chain reaction method. Serum tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), and osteocalcin (OC) levels were measured with enzyme linked-immunosorbent assay. Total antioxidant status (TAS) and total oxidative status (TOS) levels were evaluated by the routine measurement method. Results We found that lncRNA H19 expressions were upregulated in patients with CKD compared to the controls. Furthermore, lncRNA H19 relative expression levels showed a negative relationship with glomerular filtration rate (GFR) while it was positively correlated with ferritin, phosphorus, parathyroid hormone, TNF-alpha, IL-6, OC, TAS and TOS levels. Conclusion lncRNA H19 expressions were increased in CKD stage 3-5 and HD patients, and elevated lncRNA H19 expressions were associated with decreased glomerular filtration rate, inflammation, and mineralization markers in these patients.Öğe Association of UCMA levels in serum and synovial fluid with severity of knee osteoarthritis(Wiley, 2019) Okuyan, Hamza Malik; Terzi, Menderes Yusuf; Ozcan, Oguzhan; Kalacı, AydınerAim Osteoarthritis (OA) is one of the most common joint diseases causing physical disability in the aged population. OA pathogenesis is not fully known and yet there are no effective therapeutic options against OA. Upper Zone of Growth Plate and Cartilage Matrix Associated (UCMA) is a member of vitamin K-dependent protein family, and is involved in inflammation, cardiovascular diseases, cancer, and OA. In the present study, our aim was to detect serum and synovial fluid (SF) levels of UCMA and to analyze their correlation with radiographic findings and symptomatic severity in OA patients as well as the correlation between oxidative stress levels and SF UCMA levels. Methods Forty OA patients with cartilage degeneration and 20 patients with other knee joint disorders (non-OA control) were included in the present study. We used the Kellgren-Lawrence (KL) classification and Western Ontario McMaster University Osteoarthritis Index (WOMAC) scores to assess radiographic grading and symptomatic severity of OA, respectively. UCMA levels were measured in SF and serum. And also oxidative stress markers were analyzed in SF. Results SF UCMA levels of OA patients were higher compared to those of the non-OA control group and were positively correlated with radiographic finding and symptomatic severity of OA. However, there was no significant correlation between oxidative markers of SF and the KL grade, WOMAC scores, and SF UCMA levels in OA patients. Conclusion There is a close connection between UCMA SF levels and symptomatic and radiographic severities of knee OA. Therefore, UCMA can be a promising biomarker in the diagnosis and/or prognosis of OA disease.Öğe Biological behaviors of muscarinic receptors in mesenchymal stem cells derived from human placenta and bone marrow(Mashhad Univ Med Sciences, 2020) Yegani, Arash Alizadeh; Maytalman, Erkan; Kozanoglu, Ilknur; Terzi, Menderes Yusuf; Aksu, FaziletObjective(s): Cells perform their functional activities by communicating with each other through endogenous substances and receptors. Post-translation, stem cells function properly in new host tissue by carrying specific cell surface receptors. We aimed to characterize muscarinic receptor subtypes in mesenchymal stem cells (MSCs) together with osteogenic and adipogenic differentiation markers. Materials and Methods: mRNA levels of 5 muscarinic receptor subtypes (CHRM1 to 5), BMP-6, and PPAR gamma during osteogenic and adipogenic differentiation, under the effect of atropine blockade, were measured in MSCs obtained from human fetal membrane (FM) and bone marrow (BM). Additionally, the effect of atropine on differentiation in the 1st, 2nd, and 3rd passages of MSCs, obtained from human FM and BM, were analyzed by RT-qPCR. Results: CHRM1 mRNA levels increased in the FM group, while decreasing in the BM group. We found significant decreases in CHRM3 and CHRM5 mRNA levels in FM and BM groups, respectively. Atropine had variable effects based on cell source and receptor type. BMP-6 mRNA levels in differentiated osteogenic cells increased significantly compared to undifferentiated cells in both FM and BM groups. In MSCs derived from both sources, PPAR gamma mRNA levels in differentiated adipogenic cells increased significantly. Atropine showed no effect on MSCs differentiation. Conclusion: These results indicate that expressions of muscarinic receptors in MSCs derived from BM and FM can vary and these cells keep the potential of osteogenic and adipogenic differentiation in vitro. Besides, atropine had no effect on adipogenic and osteogenic differentiation of MSCs.Öğe Can atypical response in endothelial dysfunction-related genes and microRNAs arise from low hydrogen peroxide exposure?(Aepress Sro, 2024) Urhan-kucuk, Meral; Terzi, Menderes YusufOBJECTIVE: Vascular endothelium is a tissue in which several vasoactive substances are produced and secreted. Reactive oxygen species can cause endothelial dysfunction (ED). miRNAs can be implicated in the oxidative stress-related ED during vascular disease pathogeneses. Our aim is to investigate effect of H2O2- induced oxidative stress on expression levels of genes and miRNAs that are key players in ED. METHODS: H2O2 effect on cell viability of human umbilical-vein endothelial cells (HUVEC) at 24-hour was measured with MTT. Low sub-cytotoxic H2O2 concentrations (25, 50 mu M) were selected to analyze their oxidative stress-inducing capacities with MDA assay and their effects on EDN1, NOS3, VCAM1, SERPINE1, miR21, miR22, miR126, and miR146a levels with RT-qPCR. RESULTS: Each tested H2O2 concentration reduced HUVEC cell viability. Fifty mu M H2O2 augmented cellular MDA levels. Intriguingly, EDN1, VCAM1, and SERPINE1 and all analyzed miRNAs' levels attenuated upon H2O2 treatment whereas there was no change in NOS3 levels compared to control. There was a positive correlation between miR-21 and VCAM1. CONCLUSION: Rat her than individual alterations in analyzed parameters, consistent changes in our findings i.e., parallel decreases in EDN1, VCAM1, SERPINE1 mRNA levels as well as miRNAs, suggests that H2O2 concentration-dependent modulation of expression patterns can bring about various impacts on ED (Tab. 1, Fig. 5, Ref. 63). Tex t in PDF www.elis.skÖğe The cell fate: senescence or quiescence(Springer, 2016) Terzi, Menderes Yusuf; Izmirli, Muzeyyen; Gogebakan, BulentSenescence and quiescence are frequently used as interchangeable terms in the literature unwittingly. Despite the fact that common molecules play role in decision of cell cycle arrest, senescent and quiescent cells have some distinctive phenotypes at both molecular and morphological levels. Thus, in this review we summarized the features of senescence and quiescence with respect to visual characteristics and prominent key molecules. A PubMed research was conducted for the key words; senescence'', quiescence'' and cell cycle arrest''. The results which are related to cell cycle control were selected. The selection criteria of the target articles used for this review included also key cell cycle molecules such as p53, pRB, p21, p16, mTOR, p27, etc. The results were not evaluated statistically. The mechanistic target of rapamycin (mTOR) has been claimed to be key molecule in switching on/off senescence/quiescence. Specifically, although maximal p53 activation blocks mTOR and causes quiescence, partial p53 activation sustains mTOR activity and causes senescence subsequently. In broader perspective, quiescence occurs due to lack of nutrition and growth factors whereas senescence takes place due to aging and serious DNA damages. Contrary to quiescence, senescence is a degenerative process ensuing a certain cell death. We highlighted several differences between senescence and quiescence and their key molecules in this review. Whereas quiescence (cell cycle arrest) is only one half of the senescence, the other half is growth stimulation which causes actual senescence phenotype.Öğe Comparison of the protective effect of the upper zone of the growth plate and unique cartilage matrix-associated protein with hyaluronic acid and corticosteroids on an experimental rat osteoarthritis model(Turkish League Against Rheumatism, 2024) Gokdemir, Cemil Emre; Okuyan, Hamza Malik; Karaboga, Ihsan; Terzi, Menderes Yusuf; Kalacı, AydınerObjectives: This study sought to compare the protective effect of the upper zone of the growth plate and unique cartilage matrix-associated protein (UCMA) with hyaluronic acid (HA) and corticosteroids (CS) in a rat model of osteoarthritis (OA). Materials and methods: In the experimental animal study, 40 adult male rats were randomly assigned into five groups: control, monosodium iodoacetate (MIA) + vehicle (MIA+V), MIA+HA, MIA+CS, and MIA+UCMA. The OA model was induced by an intra-articular MIA injection to the right knee, and intra-articular injections into the right knee were performed on the treatment groups seven times every three days for 21 days. The knee joints were taken for histopathology and immunohistochemistry (IHC) analyses after the rats were sacrificed. All sections were stained with hematoxylin-eosin, safranin O and fast green FCF, and toluidine blue, and bone morphogenetic protein 2 (BMP-2) and nuclear factor-kappa B (NF-kappa B) expressions were analyzed with IHC. The Mankin scoring was utilized to determine the histopathological changes in the joint tissues. Results: Mankin score was significantly higher in the MIA group compared to the control group. Histopathologically, in the UCMA-, HA-, and CS-treated groups, degenerations in the articular cartilage were milder than in the MIA+V group. Mankin score was found to be decreased significantly in the UCMA-, HA-, and CS-treated groups compared to the MIA group. Furthermore, IHC analyses revealed that NF-kappa B and BMP-2 expressions elevated in the MIA-induced OA model, while they were downregulated after UCMA, HA, and CS treatments. Conclusion: Our data revealed that UCMA could be used as a potential protective molecule in the prevention and treatment of OA. Furthermore, the protective effect of UCMA was similar to HA and CS, and its possible beneficial roles against OA may be linked to the reduced BMP-2 and NF-kappa B levels. Further experimental research would make significant contributions to a better understanding of the therapeutic effect of UCMA on degenerative cartilage tissues.Öğe The effect of fingolimod (Fty720) treatment on liver enzyme levels in relapsing-remitting multiple sclerosis patients(Duzce University Medical School, 2020) Tap, Duygu; Terzi, Menderes Yusuf; Duman, TaşkınAim: Multiple sclerosis (MS) is a chronic inflammatory pathology affecting the central nervous system. Many therapeutic options have been approved against MS until today. In this study, it was aimed to investigate the effect of fingolimod treatment (FT) on the liver enzyme levels of relapsing-remitting multiple sclerosis (RRMS) patients. Material and Methods: Body mass index, FT (0.5 mg/day) duration, and liver enzyme (alanine aminotransferase, ALT; gamma glutamyl transferase, GGT) levels of 102 RRMS patients (66 female, 36 male, mean age was 40.9±10.9 years) were gathered from polyclinic records retrospectively. Results: The FT duration of MS patients was between 0.5 and 6 years. Increased ALT and GGT levels were detected in RRMS patients after >3 month-long FT. After FT, ALT and GGT levels elevated in males almost 2 times higher than in females. It was observed that ALT and GGT levels increased by 1.3 and 1.5 times in females, while 1.6 and 1.9 times in males, respectively. Of the MS patients with increased transaminases post-FT, 7 (23.3%) males and 8 (17.4%) females were at upper limit of normal for ALT whereas 9 (34.6%) males and 14 (32.6%) females as for GGT. Age and FT duration did not affect ALT and GGT levels. Conclusion: Overall, FT elevated ALT and GGT levels of RRMS patients. Thus, it is of high importance to monitor MS patients throughout FT. So that, we suggest tracking ALT and GGT levels during and after FT to prevent possible liver damage or the occurrence of other systemic diseases. © 2020, Duzce University Medical School. All rights reserved.Öğe The Effect of Fingolimod (FTY720) Treatment on Liver Enzyme Levels in Relapsing-Remitting Multiple Sclerosis Patients(2020) Tap, Duygu; Terzi, Menderes Yusuf; Duman, TaşkınAim: Multiple sclerosis (MS) is a chronic inflammatory pathology affecting the centralnervous system. Many therapeutic options have been approved against MS until today. In thisstudy, it was aimed to investigate the effect of fingolimod treatment (FT) on the liver enzymelevels of relapsing-remitting multiple sclerosis (RRMS) patients.Material and Methods: Body mass index, FT (0.5 mg/day) duration, and liver enzyme(alanine aminotransferase, ALT; gamma glutamyl transferase, GGT) levels of 102 RRMSpatients (66 female, 36 male, mean age was 40.9±10.9 years) were gathered from polyclinicrecords retrospectively.Results: The FT duration of MS patients was between 0.5 and 6 years. Increased ALT andGGT levels were detected in RRMS patients after >3 month-long FT. After FT, ALT and GGTlevels elevated in males almost 2 times higher than in females. It was observed that ALT andGGT levels increased by 1.3 and 1.5 times in females, while 1.6 and 1.9 times in males,respectively. Of the MS patients with increased transaminases post-FT, 7 (23.3%) males and8 (17.4%) females were at upper limit of normal for ALT whereas 9 (34.6%) males and 14(32.6%) females as for GGT. Age and FT duration did not affect ALT and GGT levels.Conclusion: Overall, FT elevated ALT and GGT levels of RRMS patients. Thus, it is of highimportance to monitor MS patients throughout FT. So that, we suggest tracking ALT and GGTlevels during and after FT to prevent possible liver damage or the occurrence of other systemicdiseases.Öğe Effect of Pro-Inflammatory Cytokine IL-1?, on Urotensin II Gene Expression in Human Lung Cancer Cells(Duzce Univ, 2018) Okuyan, Hamza Malik; Terzi, Menderes Yusuf; Guneri, Cansu Onlen; Kucuk, Meral UrhanObjective: Lung cancer is the deadliest cancer type world-wide. Poor prognosis of lung cancer patients and lack of an effective treatment require detailed understanding of lung cancer pathogenesis. It was highlighted in some studies that U-II is likely to be a biomarker or molecular target for the prevention and treatment of some diseases such as lung cancer. But its molecular action mechanism has not been elucidated yet. In the present study, we aimed to investigate the role of U-II in lung cancer. Methods: In our study, A549 cells were induced with different doses of IL-1 beta at different durations (1, 3 ng/ml; 6, 24 hours). mRNA levels of GAPDH, NF-kappa B1, MMP-1, and U-II were analyzed with RT-qPCR. The Delta Delta Ct (Delta Delta Ct) method was used for data analysis. The analyzed data were expressed as the fold-change. Results: Our results indicate that U-II gene is expressed in A549 cells and IL-1 beta can induce gene expressions of U-II, MMP-1 and NF-kappa B1 in A549 cells. Conclusions: U-II is a promising molecular target in treatment and prevention of lung cancer. Therefore, further studies are needed to enlighten molecular mechanism of U-II in lung adenocarcinoma.Öğe In vitro apoptotic and antiproliferative effects of propranolol on human breast cancer cells(Natl Inst Science Communication-Niscair, 2024) Alizade, Ares; Terzi, Menderes YusufBreast cancer is an issue of concern with increasing incidence among women worldwide. Propranolol, as an antihypertensive drug, exerts anticancer effects too. We conducted this study to analyze the in vitro apoptotic and antiproliferative effects of propranolol in human MCF-7 breast cancer cells. MCF-7 cells were seeded into 6 -well plates and treated with 50 mu L propranolol for 24 hours. After cell homogenization, the levels of pro-apoptotic proteins BCL2 associated X (BAX), apoptosis inducing factor (AIF), C/-EBP homologous protein (GADD153), and glucose -regulated protein 78 (GRP78), anti-apoptotic protein BCL2 apoptosis regulator (BCL-2), and cycle -regulator WEE1 G2 checkpoint kinase (WEE1) were measured with ELISA. Propranolol significantly upregulated pro-apoptotic proteins AIF, BAX, GADD153, and GRP78 while downregulated anti-apoptotic protein BCL2. The level of WEE1, as the main regulatory cell cycle protein at the G2/M checkpoint, significantly increased after propranolol treatment. Propranolol inhibited the proliferation of MCF-7 human breast cancer cells by upregulating pro-apoptotic factors AIF, BAX, GADD153 and GRP78 and by downregulating antiapoptotic BCL2. Elevated WEE1 levels after propranolol treatment might lead the tumor cells into a sustained cell -cycle arrest which eventually resulted in caspase-dependent or -independent mitochondrial or endoplasmic-reticulum stress -induced apoptosis. So, propranolol can be utilized as a potential therapeutic agent in breast cancer therapy.Öğe In vivo protective effects of upper zone of growth plate and cartilage matrix associated protein against cartilage degeneration in a monosodium iodoacetate induced osteoarthritis model(Canadian Science Publishing, 2020) Okuyan, Hamza Malik; Terzi, Menderes Yusuf; Karaboga, Ihsan; Dogan, Serdar; Kalacı, AydınerOsteoarthritis (OA) is a degenerative disease affecting the majority of over 65 year old people and characterized by cartilage degeneration, subchondral abnormal changes, and inflammation. Despite the enormous socioeconomic burden caused by OA, currently, there is no effective therapy against it. Upper zone of growth plate and cartilage matrix associated protein (UCMA) is a vitamin K dependent protein and has a critical role in pathophysiological conditions associated with bone and cartilage. However, there is no research on the protective role of intra-articular UCMA treatment in OA pathogenesis. Therefore, we aimed to investigate the potential therapeutic role of UCMA in an in vivo model of OA. We report for the first time that intra-articular UCMA injection ameliorated cartilage degeneration in a monosodium iodoacetate induced OA rat model. Furthermore, the OA-induced activation of nuclear factor kappa B and bone morphogenetic protein 2 signals was attenuated by UCMA. Our results indicated that UCMA decreased cartilage oligomeric matrix protein levels but did not affect interleukin 6, total antioxidant status, and total oxidant status levels in the serum. In conclusion, UCMA exhibited a therapeutic potential in the treatment of OA. This protective effect of UCMA is possibly achieved by reducing the aggrecanase activity and the production of inflammatory cytokines.Öğe Investigation of Anti-Inflammatory Effects of Myrtus Communis L. Essential Oil on IL-1? Induced Human Bronchial Epithelial Cell Line: Experimental Study(Turkiye Klinikleri, 2021) Gülbol Duran, Gülay; Terzi, Menderes YusufObjective: Inflammation is the primary biological response of immune system against infection, injury, and irritation, but when it is not curbed, it can lead to autoimmune and neurodegenerative diseases or cancer. Myrtus communis L. (MC) is an aromatic plant raised in the re-gion of Mediterranean Sea and bearing several pharmacological activities. We aimed in this study to investigate anti-inflammatory effects of MC essential oil that is often utilized by the local population. Material and Methods: Cell culture experiments were conducted with healthy bronchial epithelial lung cell line (BEAS-2B). The cells were grouped in three as follows; non-treated control, interleukin-1 beta (IL-1?) induced inflammatory cells, and MC-treated inflammatory cells. Non-cytotoxic concentrations of MC were determined with MTT assay. The gene expression levels of IL-6, IL-10, inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-?), cyclooxygenase-2 (COX-2), and nuclear factor kappa b (NF?B) were analyzed with reverse transcriptase-quantitative polymerase chain reaction. The protein levels of IL-6, IL-10, iNOS, and TNF-? were detected with ELISA. Results: The elevated mRNA levels of IL-6, IL-10, and NF?B in IL-1?-induced inflammatory cells significantly reduced back to the basal levels after MC treatment. In line with the mRNA levels, the protein levels of IL-6 and IL-10 significantly increased in inflammatory cells. MC treatment reversed this increase in protein levels to the baseline as in the control group. Conclusion: We demonstrated in our study the anti-inflammatory effects of MC essential oil on BEAS-2B cells by inhibiting the expression of pro-inflammatory cytokines. To be able suggest MC essential oil as a potential therapeutic agent with a strong anti-inflammatory action, further studies testing several concentrations are warranted. © 2021 by Türkiye Klinikleri.Öğe Investigation of New Benzimidazole Derivative Compounds' Effects on A549 Cell Line(Inst Tecnologia Parana, 2020) Duran, Gulay Gulbol; Kucuk, Meral Urhan; Algul, Oztekin; Terzi, Menderes YusufChronic inflammation is a common indication of several diseases, e.g. asthma, chronic obstructive pulmonary disease (COPD), atherosclerosis, etc. Benzimidazole derivatives are preferable compounds to design new analgesic and anti-inflammatory substances due to their unique biological features. We aimed to investigate the effect of a newly synthesized benzimidazole derivative, ORT-83, on A549 human lung adenocarcinoma cell line. ORT-83 was synthesized, and a non-cytotoxic concentration of ORT-83 on A549 cells was detected with MTT assay. To analyze the anti-inflammatory effect of ORT-83, an inflammatory cell culture model was established by stimulating A549 cell line with IL1-beta (10 ng/ml). After 2 hours of treatment with IL1-beta to induce inflammation, A549 cells were exposed to ORT-83 (0.78 mu g/ml) for 24 hours. Thereafter gene expression analyses were performed with qRT-PCR. We found that ORT-83 significantly suppressed the gene expression levels of the proinflammatory cytokines; IL-6, NFkB, and TNF-alpha. However, the increased levels of IL-10 (2.8 folds) by IL-1 beta induction did not change after ORT-83 and/or dexamethasone (Dex: positive control) treatments. While Dex; a COX-2 inhibitor, reduced the COX-2 expression level in inflammatory cells from 10.03 folds to 0.71 folds, ORT-83 reduced its level to 4.37 folds. iNOS expression levels did not change in any experimental groups. In conclusion, we showed that ORT-83 exerted its anti-inflammatory effects by repressing the gene expression of proinflammatory cytokines in the inflammation-induced A549 cell line. Although ORT-83 had a weaker COX-2 inhibitory effect compared to Dex, it was shown to be still a strong anti-inflammatory compound.Öğe Myrtus communis L. Esansiyel Yağının IL-1? ile Uyarılmış İnsan Bronşiyal Epitel Hücre Hattında Antiinflamatuar Etkilerinin Araştırılması: Deneysel Çalışma(2021) Duran, Gülay Gülbol; Terzi, Menderes YusufAmaç: İnflamasyon, bağışıklık sisteminin enfeksiyona, yaralanmaya veya tahrişe ilk biyolojik tepkisi olmakla birlikte kontrol edilemediğinde otoinflamatuar ve nörodejeneratif hastalıklara veya kansere neden olabilir. Myrtus communis L. (MC) Akdeniz bölgesinde yetişen, çokça farmakolojik aktivitesi olan aromatik bir bitkidir. Bu çalışmada, halk arasında sıklıkla kullanılan MC esansiyel yağının antiinflamatuar etkisini araştırmayı amaçladık. Gereç ve Yöntemler: Sağlıklı insan bronşiyal epitel hücre hattı (BEAS-2B) ile hücre kültürü çalışmaları yapıldı. Hücreler; kontrol, interlökin-1 beta (IL-1?) ile inflamatuar hâle getirilen BEAS-2B hücreleri ve MC uygulanan inflamatuar BEAS-2B hücreleri olmak üzere 3 farklı gruba ayrıldı. MC’nin sitotoksik olmayan konsantrasyonları MTT testi ile belirlendi. IL-6, IL-10, uyarılabilir sitrik oksit sentaz [inducible nitric oxide synthase (iNOS)], tümör nekrozis faktör alfa (TNF-?), siklooksigenaz-2 [cyclooxygenase-2 (COX-2)] ve nükleer faktör kappa B (NF?B) genlerinin ekspresyon düzeyleri revers transkriptaz-kantitatif polimeraz zincir reaksiyonu ile saptandı. IL-6, IL-10, iNOS ve TNF-? protein düzeyleri ELISA ile ölçüldü. Bulgular: IL-1? ile uyarılmış inflamatuar hücrelerde artan IL-6, IL-10 ve NF?B mRNA düzeyleri, MC yağı uygulama sonrası anlamlı derecede azalarak bazal seviyelere dönmüştür. IL-6 ve IL-10 protein düzeyleri gen ekspresyon verileriyle uyumlu olarak inflamatuar hâle getirilen grupta artmış olarak saptandı. MC uygulaması inflamatuar hücrelerdeki artan protein düzeylerini kontrol gurubundaki bazal seviyeye döndürdü. Sonuç: Çalışmamızda, MC esansiyel yağının BEAS-2B hücrelerinde proinflamatuar sitokinlerin ekspresyonunu inhibe ederek, antiinflamatuar etkiye sahip olduğunu gösterdik. MC esansiyel yağının güçlü bir antiinflamatuar etkiye sahip potansiyel bir terapötik ajan olarak değerlendirilmesi için farklı konsantrasyonlarla daha fazla araştırma yapılmalıdır.Öğe Myrtus communis L. essential oil reduced colony formation and altered cell differentiation markers in lung cancer spheroids(Taylor & Francis Ltd, 2023) Terzi, Menderes Yusuf; Gulbol-Duran, GulayIt was aimed to investigate the effect of Myrtus communis L. (MC) essential oil on cancer spheroids derived from A549 cells by analyzing cell viability and expression levels of prominent cancer stem cell and apoptosis markers. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide assay was per-formed to analyze cytotoxicity of MC essential oil for 24-h and 72-h. A549 cells were cultured in plates with low adherence to obtain spheroids. The effect of MC essential oil was assessed on the clonogenicity of the spheroids. Quantitative reverse-transcription polymerase chain reaction method was utilized to measure relative expressions of cluster of differentiation 44 (CD44), prominin-1 (PROM1), POU class 5 homeobox 1 (POU5F1), ATP binding cassette subfamily G member-2 (ABCG2), and caspase-3 (CASP3). Relative protein levels of ABCG2 and CASP3 were also evaluated with Western blot analysis. MC essential oil reduced cell viability of A549 cells after 24-h and 72-h. A reduction was observed in number of cancer spheroids after MC essential oil treatment for 7 days. After 24h of MC essential oil treatment, PROM1, POU5F1, ABCG2, and CASP3 gene expressions decreased while returned to basal levels after 72h. CD44 levels did not change upon MC essential oil treatment. ABCG2 protein level reduced after 24-h MC essential oil treatment and returned to its basal level after 72-h. CASP3 protein levels did not change at either time points. MC essential oil exerted its anti-tumorigenic effects onto lung cancer spheroids derived from A549 cells by reducing cell viability of cancer cells, inhibiting spheroid formation efficiency, and downregulating several cancer stem cell markers.Öğe Pigment Epithelium-Derived Factor Improves Paracellular Blood-Brain Barrier Integrity in the Normal and Ischemic Mouse Brain(Springer/Plenum Publishers, 2020) Riabinska, Arina; Zille, Marietta; Terzi, Menderes Yusuf; Cordell, Ryan; Nieminen-Kelhae, Melina; Klohs, Jan; Pina, Ana LuisaPigment epithelium-derived factor (PEDF) is a neurotrophic factor with neuroprotective, antiangiogenic, and antipermeability effects. In the brain, blood-brain barrier (BBB) function is essential for homeostasis. Its impairment plays a crucial role in the pathophysiology of many neurological diseases, including ischemic stroke. We investigated (a) whether PEDF counteracted vascular endothelial growth factor (VEGF)-induced BBB disruption in the mouse brain, (b) the time course and route of BBB permeability and the dynamics of PEDF expression after cerebral ischemia, and (c) whether intraventricular infusion of PEDF ameliorated brain ischemia by reducing BBB impairment. C57Bl6/N mice received intraparenchymal injections of CSF, VEGF, or a combination of VEGF and PEDF. PEDF increased paracellular but not transcellular BBB integrity as indicated by an increase in the tight junction protein claudin-5. In another group of mice undergoing 60-min middle cerebral artery occlusion (MCAO), transcellular BBB permeability (fibrinogen staining in the absence of a loss of claudin-5) increased as early as 6 h after reperfusion. PEDF immunofluorescence increased at 24 h, which paralleled with a decreased paracellular BBB permeability (claudin-5). PEDF after MCAO originated from the blood stream and endogenous pericytes. In the third experiment, the intraventricular infusion of PEDF decreased edema and cell death after MCAO, potentially mediated by the improvement of the paracellular route of BBB permeability (claudin-5) in the absence of an amelioration of Evans Blue extravasation. Together, our data suggest that PEDF improves BBB function after cerebral ischemia by affecting the paracellular but not the transcellular route. However, further quantitative data of the different routes of BBB permeability will be required to validate our findings.Öğe Pigment Epithelium-Derived Factor Improves Paracellular Blood-Brain Barrier Integrity in the Normal and Ischemic Mouse Brain (vol 16, pg 513, 2020)(Springer/Plenum Publishers, 2020) Riabinska, Arina; Zille, Marietta; Terzi, Menderes Yusuf; Cordell, Ryan; Nieminen-Kelhae, Melina; Klohs, Jan; Pina, Ana Luisa[Abstract Not Available]Öğe Propranolol Treatment Reduces A549-Derived Lung Cancer Spheroids via Intrinsic Apoptosis(Erciyes Univ Sch Medicine, 2023) Terzi, Menderes YusufObjective: Propranolol (PRO), a non-selective beta-adrenergic receptor inhibitor, has been recently discovered to possess anti-tumorigenic effects in cancer patients. Therefore, we aimed to investigate the in vitro effects of PRO in A549-derived lung cancer spheroids in terms of cell viability, spheroid formation, cell cycle regulation, cell differentiation, and apoptosis. Materials and Methods: The effect of 24-hour PRO treatment on A549 cell viability was assessed using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. A sub-cytotoxic PRO concentration (125 mu M) was employed to evaluate its impact on the clonogenicity of A549-derived cancer spheroids after seven days of incubation. Messenger Ribonucleic Acid (mRNA) levels of cell cycle regulators including cyclin-dependent kinase inhibitor 1A (p21) and G2 checkpoint kinase (WEE1), apoptotic markers such as caspases 3, 8, 9 (CASP3, CASP8, CASP9), and stem cell differentiation markers, namely POU class 5 homeobox 1 (octamer-binding transcription factor 4 (OCT4)), prominin 1 (CD133), and adenosine triphosphate (ATP) binding cassette subfamily G member 2 (ABCG2) were measured using reverse transcription quantitative polymerase chain reaction (RT-qPCR) after a 24-hour treatment of cancer spheroids with PRO. Results: PRO treatment reduced cell viability and inhibited the clonogenicity of cancer spheroids by activating intrinsic apoptotic markers CASP3 and CASP9, leading to cell cycle arrest via increased p21 expression. PRO did not significantly alter stem cell differentiation markers. Conclusion: The proliferation and clonogenic activity of lung cancer spheroids can be effectively suppressed with PRO, primarily through inducing intrinsic apoptosis following p21-mediated cell cycle arrest. While short-term PRO exposure did not affect the gene expression levels of stem cell differentiation markers, the notable decrease in both cell viability and spheroid formation efficiency suggests the potential of PRO as a therapeutic drug in lung cancer treatment.
