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Öğe 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 Beclin-1, an autophagy-related protein, is associated with the disease severity of COVID-19(Pergamon-Elsevier Science Ltd, 2021) Okuyan, Hamza Malik; Dogan, Serdar; Bal, Tayibe; Cabalak, MehmetAims: Coronavirus disease 2019 (COVID-19), which is a highly contagious disease, is an ongoing outbreak worldwide with high morbidity and mortality. The approaches targeting the autophagy processes might have promising diagnostic and therapeutic values against Coronavirus infection. Here, we aimed to investigate the relationship of Beclin-1 (BECN1), an autophagy-related protein, with blood parameters and the clinical severity in patients with COVID-19. Materials and methods: We enrolled 108 patients with COVID-19 and 21 healthy controls in this study, from September 2020 to January 2021 and divided all patients into two groups according to the severity of the disease: The non-severe group and the severe group. BECN1 levels and blood parameters were measured with Enzyme-Linked Absorbent Assay and routine techniques, respectively. Key findings: Serum BECN1 levels were increased in patients with COVID-19 compared to the healthy controls, and its concentrations were significantly higher in the severe group than in the non-severe group (p < 0.001). BECN1 levels showed a significantly positive correlation with coagulation markers such as D-dimer and Fibrinogen (FIB) and inflammation markers such as C-reactive protein (CRP), Procalcitonin (PCT), Ferritin and biochemical markers such as Blood urea nitrogen and Lactate dehydrogenase (p < 0.001). We detected that areas under the ROC curve for BECN1, D-dimer, FIB, PCT, CRP and Ferritin were 0.8662, 0.9110, 0.8278, 0.9996 and 0.9284, respectively (p < 0.0001). Significance: BECN1 may serve as a predictive biomarker in evaluating the disease severity of COVID-19. Our data suggest that BECN1 mediated-autophagy modulation might have a promising value in improving the clinical outcomes of COVID-19.Öğe Borik asit uygulamasının sıçan böbrek ve testis dokusunda oluşturduğu hasara karşı omega-3 yağ asitlerinin koruyucu etkisinin histopatolojik olarak incelenmesi(2014) Nacar, Ahmet; Selçuk, Yasin; Okuyan, Hamza Malik; Sefil Kaplan, Nebihat; Deligönül, Erkan; Nacar, EmelAmaç: Bu çalışmada borik asitin böbrek ve testis dokuları üzerine toksik etkilerine karşı omega-3 yağ asitlerinin koruyucu etkileri araştırıldı. Yöntemler: Çalışmada 32 adet Wistar albino rat kullanı- larak 4 grup oluşturuldu. Kontrol, Omega-3 (10 gün sü- reyle 400 mg/kg/gün), Borik asit (375 mg/kg/gün, 10 gün), Borik asit+Omega-3. Böbrek ve testis dokuları belirli histopatolojik bulguların yaygınlığına göre puanlandı. Bulgular: Histopatolojik analizde, borik asit testis ve böbrekte anlamlı derecede hasar oluşturdu. En belirgin bulgular böbrekte glomerüllerde büzülme, nekroz, kanama ve tübüler hücrelerde dejenerasyon; testiste ise seminifer tübülde hücre kaybı, hücrelerin bazal laminadan kopması ve epitel hücrelerin dejenerasyonu şeklindeydi. Omega-3 uygulaması bu hasarı belirgin bir biçimde hafifletti. Sonuç: Literatür analizimize göre bu çalışma borik asitin indüklediği böbrek ve testis hasarına karşı omega-3 yağ asitlerinin koruyucu etkilerinin gösterildiği ilk çalışmadır.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 Ebselen, an Active Seleno-Organic Compound, Alleviates Articular Cartilage Degeneration in a Rat Model of Knee Osteoarthritis(Springernature, 2023) Okuyan, Hamza Malik; Yurtal, Ziya; Karaboga, Ihsan; Kacmaz, Filiz; Kalacı, AydınerOsteoarthritis (OA) is a prevalent articular disease mainly characterized by extracellular matrix degradation, apoptosis, and inflammation, which lead to cartilage destruction and abnormal bone metabolism. With undesirable side effects, current limited symptomatic treatments are aimed at relieving pain and improving joint mobility in patients with OA. Intra-articular (IA) hyaluronic acid (HA) injection, as a nonsurgical therapy, is commonly used in the clinical management of knee OA, but the efficacy of this therapeutic option remains controversial. Ebselen has tremendous pharmacological importance for some diseases due to its antioxidant, antiapoptotic, and anti-inflammatory features. However, there is no research examining the therapeutic effect of Ebselen in OA using the rat OA model. Therefore, we aimed to investigate the therapeutic effect of Ebselen on cartilage degeneration and its role in bone morphogenetic protein 2 (BMP2) and nuclear factor kappa B (NF-kappa B) signaling in the molecular pathogenesis of OA. We induced a knee OA model in rats with an IA injection of monosodiumiodoacetate (MIA). After the treatment of Ebselen, we evaluated its chondroprotective effects by morphological, histopathological, and immunohistochemical methods and an enzyme-linked immunosorbent assay. We report for the first time that Ebselen treatment alleviated articular cartilage degeneration in the rat knee OA model and reduced MIA-induced BMP2 and NF-kappa B expressions. In addition, our results unveiled that Ebselen decreased IL-beta and IL-6 levels but did not affect COMP levels in the rat serum. Ebselen could be a promising therapeutic drug for the prevention and treatment of OA by alleviating cartilage degeneration and regulating BMP2 and NF-kappa B expressions.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 Etanol uygulamasının böbrek dokusunda oluşturduğu hasar ve bu hasara karşı Omega-3 yağ asitlerinin koruyucu etkisinin incelenmesi(Hatay Mustafa Kemal Üniversitesi, 2011) Okuyan, Hamza Malik; Nacar, Ahmet; Yıldırım, AyşeÇalışmada, etanolün böbrek dokusunda oluşturduğu hasar ve bu hasara karşı omega-3 yağ asitlerinin koruyucu etkisi histolojik metotlarla incelenmiştir.Deneylerde, 250±20 ağırlığında 56 adet wistar albino erkek erişkin sıçan kullanıldı. Deney hayvanları rastgele 8 gruba ayrıldı. Gruplar; akut kontrol grubu (n=7), akut omega-3 grubu (n=7), akut etanol grubu (n=7), akut etanol + omega-3 grubu (n=7), kronik kontrol grubu (n=7), kronik omega-3 grubu (n=7), kronik etanol grubu (n=7) ve kronik etanol + omega-3 grubudur (n=7). Serum fizyolojik, etanol (3 g/kg/gün) ve omega-3 yağ asidi (400 mg/kg/gün) akut gruplara 3 gün kronik gruplara ise 15 gün boyunca oral yolla uygulandı. Deneylerin sonunda böbrek dokuları ışık mikroskobik inceleme için çıkarıldı.Böbrek dokularının fiksasyonu %10 tamponlanmış nötral formaldehit ile yapıldıktan sonra rutin histolojik teknikler uygulandı ve dokular Hematoksilen-Eosin (H&E) ve Periodik Asit-Schiff (PAS) boyama metoduyla görüntülendi. Rastgele sistematik örnekleme yapıldıktan sonra preparatlar skorlama yapılarak değerlendirildi. Bowman aralığının değerlendirilmesinde ise her gruptan 100 farklı böbrek cisimciği ölçüm yapılarak incelendi. Yapılan bu incelemeler one way ANOVA ile değerlendirildi.Elde edilen bulgulara göre; kronik etanol grubu dokularında konjesyon, Bowman aralığında daralma, hiperselülerite, tübül hasarı, glomerül hasarı ve vakuolizasyon histopatolojik bulguları tespit edildi. Kronik etanol+omega-3 grubunda ise histopatolojik bulgular azalmıştı. Akut gruplarda belirgin bir histopatolojik değişiklik yoktu. Histolojik incelemeler istatistiksel sonuçlar ile uyumluydu.Sonuç olarak omega-3 yağ asitlerinin etanolün oluşturduğu nefrotoksisiteyi önlediği tespit edildi.Öğe Expression level of UCMA as a candidate molecular targetin osteoarthritis(2021) Okuyan, Hamza Malik; Arslan, Ahmet; Iğcı, Yusuf Ziya; Göğebakar, Bülent; Bilgiç, Nilüfer; Gündüz, Kübra; Sönmez, DilaraAim: Osteoarthritis (OA) is a degenerative joint disorder that damages cartilage, synovium and subchondral bone, and there is yet no effective treatment for OA. The identification of novel therapeutic methods is crucially needed for better treatment of OA. Upper zone of growth plate and cartilage matrix associated (UCMA) was discovered as a chondrocyte specific protein in 2008, but its expression is solely not specific to cartilage tissue. Although UCMA is implicated in cartilage and bone metabolic processes, the molecular function of UCMA in OA is not elucidated yet. We aimed to examine the potential effect of UCMA in osteoblast metabolism associated with OA. Materials and Methods: We created an in vitro OA model by inducing osteoblast cell line with IL-1?. The expression levels of 12 related genes were determined using the qRT-PCR method. The MMP1 and OPG expression levels in the supernatants of cells were detected with ELISA. Results: We found that there was a dramatic increase in the levels of UCMA expression and other OA-related markers. We showed that IL-1? triggered the expression of main transcription factors playing a role during bone formation. MMP1 and OPG synthesis and secretions were increased in IL-1? induced-hFOB1.19 cell line significantly. Conclusion: Our study, as the first one using the human osteoblast cell line, provides good evidence about the potential value of UCMA in the pathophysiology of OA and shows that UCMA can be a promising molecular target to develop therapeutic approaches for OA.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 the protective effect of erdosteine against cyclosporine-induced injury in rat liver with histological and biochemical methods(2015) Nacar, Ahmet; Karaboğa, İhsan; Okuyan, Hamza Malik; Kaplan Sefil, Nebihat; Nacar, Emel; Motor, Sedat; Akküçük, Seçkin; Özkan, Orhan VeliBackground/aim: In the present study, the protective effect of erdosteine against cyclosporine-induced injury in rat liver was investigated with histological and biochemical methods. Materials and methods: Thirty-two Wistar albino male rats were randomly divided into 4 groups: control (n = 8), cyclosporine (n = 8, 20 mg kg–1 day–1 i.p.), cyclosporine + erdosteine (n = 8, erdosteine 12 mg kg–1 day–1 orally), and erdosteine (n = 8). At the end of day 12, liver tissues were removed for histological and biochemical analysis. After liver tissues were fixed in 10% buffered neutral formalin, routine histological processes were applied and tissue sections were stained with hematoxylin and eosin, periodic acid–Schiff, and elastic fiber stain methods. One hundred lobules of liver were examined for each group and evaluated statistically. The levels of malondialdehyde and glutathione peroxidase, as well as the activities of superoxide dismutase, were determined. Results: The cyclosporine group showed significant histopathological changes compared to the control. In the cyclosporine + erdosteine group, histopathological changes of hepatic damage were markedly reduced. Histological findings were supported by biochemical results. Conclusion: Erdosteine could attenuate cyclosporine-induced liver injury.Öğe Protective effects of hesperetin on lipopolysaccharide-induced acute lung injury in a rat model(Baycinar Medical Publ-Baycinar Tibbi Yayincilik, 2020) Kaya, Serkan; Kaya, Sinem Albayrak; Polat, Elif; Erboga, Zeynep Fidanol; Duran, Yasin; Polat, Fatin Rustu; Okuyan, Hamza MalikBackground: In this experimental study, we aimed to investigate the effects of hesperetin. a natural flavonoid, on a lipopolysaccharide-induced acute lung injury model in rats. Methods: Between March 2019 and May 2019, a total of 18 adult male Wistar albino rats, weighing approximately 250 to 300 g, were randomly divided into three groups as control, lipopolysaccharide, and lipopolysaccharide + hesperetin groups (n=6 in each group). The wetidry weight ratio of lung tissue was determined. Histopathological changes were examined using light and scanning electron microscopy. Pulmonary nuclear factor-kappa beta, inducible nitric oxide synthase, and alpha-smooth muscle antigen activity were determined with indirect immunohistochemical methods. Pulmonary apoptosis was detected with the terminal deoxynucleotidyl transferase dUTP nick-end labeling method. Tumor necrosis factor-alpha. interleukin-1 beta, interleukin-6, and interleukin-10 concentrations were measured with enzyme-linked immunosorbent assay. Results: Treatment with hesperetin significantly improved the architecture of lung tissue and reduced the wet/dry weight ratio, nuclear factor-kappa beta, inducible nitric oxide synthase, and alphasmooth muscle antigen expression, pulmonary apoptosis, and levels of proinflammatory cytokines. Conclusion: Our study results suggest that hesperetin has a potent protective effect against lipopolysaccharide-induced acute lung injury in rats via suppression of the proinflammatory cytokine cascade, nuclear factor-kappa beta. signaling pathway activation, and apoptosis.Öğe Relationship of Semaphorin Proteins with Blood Markers in Patients with COVID-19(2023) Okuyan, Hamza Malik; Doğan, Serdar; Bal, Tayibe; Çabalak, MehmetAim: The COVID outbreak is a serious health problem affecting socio-economic life and healthcare systems worldwide. Although the role of Semaphorins in some diseases is relatively known, the association of these molecules with the pathogenesis of COVID-19 remains unclear. Therefore, we aimed to investigate the relationship of Semaphorins (Sema3A, Sema4A, Sema4D and Sema7A) with biochemical and inflammatory alterations and their roles in predicting the presence of disease and disease severity in COVID-19 patients. Material and Method: A total of 144 COVID-19 patients and 20 healthy individuals were enrolled in the current study. Serum Semaphorins were analyzed using Enzyme-linked Immunosorbent Assay. Other laboratory parameters were measured using routine laboratory techniques. Results: Sema3A concentrations were elevated in both patients with severe and non-severe COVID-19 groups compared with healthy controls (p<0.0001). Sema4A levels were significantly decreased in patients with the severe COVID-19 group (p=0.002). Sema3A was negatively correlated with routine hematological markers such as EOS, RBC, HGB, HCT and MCV. Further, Sema3A was positively correlated with coagulation markers such as D-dimer and fibrinogen and the inflammatory markers, such as ESR, CRP, PCT and ferritin and biochemical markers such as ALT, AST, BUN, CK and LDH. Sema4A was negatively correlated with WBC, while it was positively correlated with LYM and HCT. Sema3A levels over 3.03 ng/mL and Sema4A concentrations of less than 11.8 ng/mL may predict the presence of COVID-19 (p<0.0001, p=0.02, respectively). Conclusion: Our data presented here suggest that Sema3A and Sema4A could be diagnostic markers for COVID-19 and may have importance in the clinical management of the disease.Öğe Relationship of Thrombospondin-1 and Thrombospondin-2 with hematological, biochemical and inflammatory markers in COVID-19 patients(Walter De Gruyter Gmbh, 2023) Dogan, Serdar; Okuyan, Hamza Malik; Bal, Tayibe; Cabalak, Mehmet; Begen, Mehmet A.Objectives: Roles of Thrombospondin-1 (TSP-1) and Thrombospondin-2 (TSP-2) in tissue repair and inflammation are well-documented, but the association of their serum expressions with the pathogenesis of COVID-19 remains unclear. We investigate the roles of TSP-1 and TSP-2 in COVID-19. Methods: 106 SARS-CoV-2 infected patients and 23 healthy people were enrolled in our study. COVID-19 patients were divided into two groups as non-severe and severe. TSP-1 and TSP-2 concentrations were measured with an enzyme-linked Immunosorbent Assay, and blood markers were analyzed with routine laboratory techniques. Results: COVID-19 patients had significantly higher TSP-1 and TSP-2 levels than healthy controls. TSP-1 and TSP-2 positively correlated with inflammatory markers, including ESR, CRP, PCT, ferritin, and biochemical parameters such as ALT, AST, BUN, CK, and LDH. In addition, TSP-1 and TSP-2 were negatively correlated with hematological markers such as LYM, EOS, and HGB. Receiver operating characteristic analyses revealed that COVID-19 may be predicted with TSP-1 levels over 189.94 ng/mL and TSP-2 levels higher than 0.70 ng/mL. Conclusions: Our analysis suggests that TSP-1 and TSP-2 expressions at the systemic level may have clinical importance for COVID-19.Öğe Upper Zone of Growth Plate and Cartilage Matrix (UCMA) Levels in Patients with Chronic Kidney Disease(Inst Tecnologia Parana, 2020) Okuyan, Hamza Malik; Ozcan, Oguzhan; Dogan, Serdar; Arpaci, Abdullah; Turgut, Faruk HilmiChronic kidney disease (CKD) is an important health problem across the world affecting the adult population with an enormous social and economic burden. Calcium regulation is also affected in patients with CKD, and related to several disorders including vascular calcifications, mineral bone disorders, and cardiovascular diseases (CVD). Upper zone of growth plate and cartilage matrix (UCMA) is vitamin K-dependent protein (VKDP) and acts as a calcification inhibitor in the cardiovascular system. The molecular mechanism of UCMA action remains unclear in CKD. In the current study, we aimed to investigate serum total UCMA levels and its association with calcium metabolism parameters in CKD patients including hemodialysis (HD) patients. Thirty-seven patients with CKD stage 3-5, 41 HD patients, and 34 healthy individuals were enrolled in this cross-sectional study. Serum UCMA and calcification related protein levels (Matrix Gla Protein (MGP), Osteocalcin (OC), and Fetuin-A) were analyzed with enzyme-linked immunosorbent assay (ELISA). Calcium mineral disorder parameters (Serum Ca, P, iPTH) were quantified with routine techniques. We, for the first time, report the potential biomarker role of UCMA in CKD including HD. Serum total UCMA levels were significantly higher in patients with CKD including HD patients than the healthy controls. Also, serum UCMA levels showed negative correlations with serum calcium, and eGFR, while showed positive relationships with P, iPTH, MGP, OC. Increased total UCMA levels may have a role in the Ca metabolism disorder and related to the pathogenesis of Vascular Calcification in patients with CKD.Öğe Urotensin II (U-II), a novel cyclic peptide, possibly associated with the pathophysiology of osteoarthritis(Elsevier Science Inc, 2014) Gogebakan, Bulent; Uruc, Vedat; Ozden, Raif; Duman, Ibrahim Gokhan; Yagiz, Abdullah Erman; Okuyan, Hamza Malik; Aldemir, OzgurSynovial fibrosis is one of the main outcomes of osteoarthritis. Some authors have reported that urotensinII (U-II) may cause pathologic fibrosis in cardiovascular system, lung and liver. However there are no previous reports available in the literature about its relationship with the synovial fibrosis in osteoarthritis. The aim of this study was to compare the U-II levels in knee synovial fluids obtained from osteoarthritic and non-osteoarthritic patients. Two groups were created, the osteoarthritis group and non-osteoarthritic control group. The control group was consisted of patients who underwent arthroscopic surgery for other reasons than cartilage disorders. In the osteoarthritis group all patients had grade 4 primer degenerative osteoarthritis and were treated with total knee arthroplasty. Minimum 1 mL knee synovial fluids were obtained during operation. Levels of U-II were measured by using ELISA kit U-II levels were significantly higher in the osteoarthritic group than that in the control group. No correlation was found between U-II levels and age. In conclusion, the significantly high U-II levels in the knee synovial fluid of osteoarthritic patients supported our hypothesis that U-II may be associated with the synovial fibrosis in osteoarthritis.(c) 2014 Elsevier Inc. All rights reserved.Öğe UROTENSİN II’NİN İNSAN OSTEOBLAST HÜCRELERİNDE ENFLAMASYONLA İLİŞKİLİ ROLÜ(2021) Okuyan, Hamza Malik; Terzi, Menderes Yusuf; Duran, Gülay Gülbol; Kalacı, AydınerOsteoartrit (OA), kemik, kıkırdak ve sinoviyal dokuda katabolik değişikliklere neden olan yaygın bir eklem hastalığıdır. OA’nıngüncel tedavisi, hastalığı tamamen iyileştirmek için yeterli değildir. Eklem kondrositlerinin yanı sıra, kemik hücrelerindeki OA ile ilişkili mekanizmaların anlaşılması bu hastalığın önlenmesi ve tedavisine katkı sağlayacaktır. Urotensin II (UTS2), nörohormon benzeri aktiviteye sahip polipeptid bir moleküldür ve kardiyovasküler, pulmoner, renal ve merkezi sinir sisteminde eksprese edildiği bilinmektedir. Pek çok sistem üzerinde patofizyolojik etkileri olan UTS2’nin, OA’daki moleküler mekanizması tam olarak bilinmemektedir. Bu çalışmada, insan osteoblast hücreleri kullanılarak UTS2’nin OA patogenezindeki enflamasyonla ve apoptozis ile ilişkili rolünün incelenmesi amaçlanmıştır. Bu çalışmada, insan osteoblast hücreleri, tümör nekroz faktörü alfa (TNF-?) ve UTS2’ye maruz bırakıldı. İnkübasyon süresinin sonunda hücrelerden RNA izole edildi ve kantitatif ters transkripsiyon-polimeraz zincir reaksiyonu analizleri yapıldı. TNF-? maruziyeti, interlökin 6 ve nükleer faktör kappa B gen ekspresyon seviyelerinde anlamlıdüzeyde bir artışa neden olmuştur. UTS2 maruziyeti, kendi gen ekspresyon seviyesini azaltmıştır. TNF-a ve UTS2 maruziyetleri, Kaspaz-3 gen ekspresyonu üzerinde istatistiksel olarak anlamlı bir farklılığa neden olmamıştır. Çalışmamızda, bulgularımız; insan osteoblast hücrelerinde UTS2’nin eksprese edildiğini ve UTS2’nin hücre kültür ortamına eklenmesi bu genin kendi ekspresyon seviyeleri üzerinde etkili olabileceğini göstermektedir.Öğe Urotensin-II Prevents Cartilage Degeneration in a Monosodium Iodoacetate-Induced Rat Model of Osteoarthritis(Springer, 2022) Terzi, Menderes Yusuf; Okuyan, Hamza Malik; Karaboga, Ihsan; Gokdemir, Cemil Emre; Tap, Duygu; Kalacı, AydınerOsteoarthritis (OA) is a common degenerative articular disorder caused by traumatic or spontaneous factors such as genetics, obesity, and advanced age. Comprehending the pathogenic mechanism of OA ensures the development of novel disease-modifying therapeutics rather than conventional palliative drugs with undesired side effects. Urotensin-II (UII) is a multifunctional short cyclic peptide implicated in several disorders. We aimed to analyze the effects of intraarticular UII treatment in a monosodium iodoacetate (MIA)-induced OA rat model. We divided animals into six groups to test three different concentrations of UII with histopathological and immunohistochemical analyses of bone morphogenetic protein-2 (BMP-2), nuclear factor kappa B subunit 1 (NF-kappa B), and intrinsic UII expression. We analyzed serum levels of cartilage related and inflammatory markers post-OA. We observed a noticeable amelioration of the MIA-induced knee damage in UII-treated animals after gross morphology examination. Mankin scoring after histopathological stainings revealed a partial prevention of articular tissue damage in UII-treated animals. We found a significant reduction in BMP-2 and NF-kappa B while an increase in intrinsic UII expressions upon exogenous UII injection after immunohistochemical analyses. The Mankin scores were significantly correlated with BMP-2, NF-kappa B, and intrinsic UII levels. There was no significant alteration in serum markers after UII treatment. We are the first group showing the protective effect of UII on the destructed knee joints of osteoarthritic rats by downregulating the BMP-2 and NF-kappa B and upregulating intrinsic UII expressions. To uncover the mechanistic role of UII during OA, further experiments are warranted. [GRAPHICS] .Öğe Urotensin-II Prevents Cartilage Degeneration in a Monosodium Iodoacetate-Induced Rat Model of Osteoarthritis (vol 28, 140, 2022)(Springer, 2024) Terzi, Menderes Yusuf; Okuyan, Hamza Malik; Karaboga, Ihsan; Gokdemir, Cemil Emre; Tap, Duygu; Kalacı, Aydıner[Abstract Not Available]
