Browsing by Subject "Transforming Growth Factor beta1"
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Item Influence of the selective oestrogen receptor modulator (raloxifene hydrochloride) on IL-6, TNFα, TGF-β1 and bone turnover markers in the treatment of postmenopausal osteoporosis(2007) Özmen B.; Kirmaz C.; Aydin K.; Kafesciler S.O.; Guclu F.; Hekimsoy Z.Background. Osteoporosis that is encountered frequently in postmenopausal women, may cause an increased incidence of vertebral and iliac fractures that are associated with excess morbidity. Raloxifene hydrochloride, a selective oestrogen receptor modulator, has been shown to increase bone mineral density and decrease biochemical markers of bone turnover in postmenopausal women, without stimulatory effects on breast or uterus. Levels of proinflammatory cytokines, including IL-6, and TNF-α and TGF-β1 which are important cytokines involved in remodeling, have been evaluated previously in in vitro studies of osteoporosis. However, there seems to be a paucity of in vivo research concerned with changes in these cytokines in osteoporosis. Objective. In this study, we evaluated the effects of raloxifene (Evista®; Lilly Pharmaceutical Co. USA, 60 mg/day) on biochemical bone turnover markers, serum parathyroid hormone, and 25-OH vitamin D, as well as the serum levels of IL-6, TNF-α and TGF-β1, in 22 postmenopausal, osteoporotic women before and after 12 weeks of raloxifene treatment. Methods. Well-matched, postmenopausal, non-osteoporotic control subjects were also enrolled in the study. Serum levels of all the parameters were measured in postmenopausal, osteoporotic women at baseline and end of the study. Results. It was found that serum osteocalcin and parathyroid hormone, and urine deoxypyridinoline levels decreased to normal levels with treatment. Serum 25-OH vitamin D levels after treatment in the patient group were higher than those in the control group. Serum IL-6, TNF-α and TGF-β1 levels did not change significantly with treatment. However, serum levels of IL-6 and TGF-β1 in the patient group after treatment, decreased to levels lower than those found in the control group. Serum TNF-α levels in the patient group before and after treatment, were lower than those in the control group. Conclusion. Raloxifene treatment reduces bone turnover biochemical markers, parathyroid hormone and induces 25-OH vitamin D in postmenopausal women. Moreover, it also affects some serum cytokine levels in the postmenopausal period.Item Methylphenidate has dose-dependent negative effects on rat spermatogenesis: Decreased round spermatids and testicular weight and increased p53 expression and apoptosis(2011) Cansu A.; Ekinci Ö.; Ekinci Ö.; Serdaroglu A.; Erdǒan D.; Co̧kun Z.K.; Gürgen S.G.In the present study, we aimed to evaluate the possible effects of methylphenidate on rat testes. Forty-two Wistar rats were randomly distributed into three experimental groups of 14 rats each. For 90 days, each group via gavage received the following: group 1 = tap water (control group), group 2 = 5 mg/kg/day of ritalin (methylphenidate, MPH), and group 3 = 10 mg/kg/day of ritalin. After sacrificing the animals, the body weights as well as the absolute and relative testicular weights were measured. Testes were sampled, fixed, and processed and, by histopathological examination, quantitative morphometric analysis of Sertoli cells, spermatocytes, and spermatids was performed in stages II, V, and XII. Immunohistochemistry was performed for transforming growth factor (TGF)-β1 and p 53, and the apoptotic index was assessed through the TUNEL method. Group 2 had a reduction of round spermatids in stage II. Group 3 had reduction in both stage II and stage V spermatids, as well as lower testicular weight. The p 53 expression was increased in group 3. In groups 2 and 3, the TGF-β1 expression was reduced and the apoptotic index by TUNEL was increased. Body weights remained stable on either group. Our results showed that methylphenidate might negatively affect spermatogenesis not only by reducing testicular weight and amount of round spermatids but also by increasing apoptotic death and p 53 activation. The findings of the study, however, must be cautiously interpreted. © SAGE Publications 2011.Item Statin treatment reduces oxidative stress-associated apoptosis of sciatic nerve in diabetes mellitus(2011) Grpinar T.; Ekerbiçer N.; Harzadin N.U.; Barut T.; Tarakçi F.; Tuglu M.I.Statins are lipid-lowering drugs that are widely used for treating hyperlipidemia, especially in diabetic patients. The aim of our study was to explore the effects of atorvastatin on oxidative stress and apoptosis in the sciatic nerve due to hyperglycemia. Diabetes was induced by streptozotocin. Atorvastatin was given orally for two weeks beginning from the sixth week. Microscopic examination of sciatic nerve revealed that normal tissue organization was disrupted in streptozotocin induced diabetic rats. Treatment with Atorvastatin reduced the histological damage and protected the morphological integrity of the sciatic nerve in streptozotocin induced diabetes. Increased expressions of transforming growth factor beta-1, endothelial nitric oxide synthase and TUNEL in sciatic nerve from streptozotocin induced diabetes were reduced by Atorvastatin. Atorvastatin could improve the effects of oxidative stress and apoptosis on the sciatic nerve due to diabetes. © 2011 The Biological Stain Commission.Item Cancer stem cell differentiation: TGFβ1 and versican may trigger molecules for the organization of tumor spheroids(Spandidos Publications, 2014) Oktem G.; Sercan O.; Guven U.; Uslu R.; Uysal A.; Goksel G.; Ayla S.; Bilir A.Cancer stem cells (CSCs) have the ability to self-renew similar to normal stem cells. This process is linked with metastasis and resistance to chemotherapy and radiotherapy. In the present study, we constructed an in vitro differentiation model for CSCs. CSCs isolated and proliferated for one passage were maintained as monolayers or spheroid-forming cells with serum included media for differentiation process. Differentiation of adhesion molecules and cellular ultrastructural properties were investigated and compared in both monolayer and spheroid cultures. CD133+/CD44+ cancer-initiating cells were isolated from DU-145 human prostate cancer cell line monolayer cultures and propagated as tumor spheroids and compared with the remaining heterogeneous cancer cell bulk population. Microarray-based gene expression analysis was applied to determine genes with differential expression and protein expression levels of candidates were analyzed by immunohistochemistry. Electron microscopy showed detailed analysis of morphology. TGFβ1 was found to be significantly upregulated in monolayer CSCs. High expression levels of VCAN, COL7A1, ITGβ3, MMP16, RPL13A, COL4A2 and TIMP1 and low expression levels of THBS1, MMP1 and MMP14 were detected when CSCs were maintained as serum-grown prostate CSC spheroids. Immunohistochemistry supported increased immunoreactivity of TGFβ1 in monolayer cultures and VCAN in spheroids. CSCs were found to possess multipotential differentiation capabilities through upregulation and/or downregulation of their markers. TGFβ1 is a triggering molecule, it stimulates versican, Col7A1, ITGβ3 and, most importantly, the upregulation of versican was only detected in CSCs. Our data support a model where CSCs must be engaged by one or more signaling cascades to differentiate and initiate tumor formation. This mechanism occurs with intracellular and extracellular signals and it is possible that CSCc themselves may be a source for extracellular signaling. These molecules functioning in tumor progression and differentiation may help develop targeted therapy.Item A novel association between TGFb1 and ADAMTS4 in coronary artery disease: A new potential mechanism in the progression of atherosclerosis and diabetes(2015) Uluçay S.; Çam F.S.; Batır M.B.; Sütçü R.; Bayturan Ö; Demircan K.OBJECTIVE: Coronary artery disease is characterized by atherosclerosis in the vessel wall. Recently, it has been thought that increasing LDL-binding capacity of subendothelial proteoglycan fragments that are formed by protease activity can be responsible for the initiation of atherosclerosis. ADAMTS4 is a member of the versican-degrading proteinases. In vitro studies demonstrated that TGFb inhibits the expression of ADAMTS4 in macrophages. In this study, we aimed to investigate the role and association between TGFb1 and ADAMTS4 in coronary artery disease.; METHODS: A total of 84 cases with atheroma plaque and 72 controls without plaque were analyzed. The severity of disease was determined by Gensini score. TGFb1 gene polymorphisms were genotyped by the PCR-RFLP method. TGFb1 and ADAMTS4 serum levels were measured by ELISA method. Statistical analyses of genotypes and their relationship with serum levels were performed by chi-square, student t test and ANOVA.; RESULTS: ADAMTS4 levels were higher in cases compared with controls (p<0.05). In the patient group, ADAMTS4 levels were higher than in controls and correlated with TGFb1 serum levels (r=0.29; p<0.05) and severity of disease (r=0.20; p<0.05). The TGFb1 gene CCA haplotype was associated with 3.3-fold increase in coronary artery disease (OR=3.26 95% CI 1.22-8.68; p<0.05). Unexpectedly, ADAMTS4 serum levels were also higher in diabetic cases (p=0.05).; CONCLUSION: This study has demonstrated that ADAMTS4 may be responsible for the pathogenesis of atherosclerosis. This is the first report about the association between ADAMTS4 and TGFb1 serum levels in the progression of atherosclerosis in CAD. Furthermore, it is seen that TGFb1 haplotype can cause a genetic susceptibility to CAD in the Turkish population. To our knowledge, this is also the first report suggesting higher serum ADAMTS4 levels in diabetic patients.Item Evaluation of GCF MMP-1, MMP-8, TGF-β1, PDGF-AB, and VEGF levels in periodontally healthy smokers(Turkiye Klinikleri, 2015) Eren G.; Türkoğlu H.O.; Atmaca H.; Atilla F.G.Background/aim: The effect of smoking on inflammatory biomarkers in gingival crevicular fluid (GCF) is well established in the presence of periodontal inflammation. However, it is not clear if smoking has an influence on matrix metalloproteinase (MMP) and growth factor levels in the GCF of periodontally healthy subjects. The aim of this study was to investigate GCF levels of MMP-1, MMP8, transforming growth factor (TGF)-β1, platelet-derived growth factor (PDGF)-AB, and vascular endothelial growth factor (VEGF) in smoking versus nonsmoking periodontally healthy subjects. Materials and methods: Thirty-two periodontally healthy subjects were included in this study. Probing depths, bleeding on probing, and plaque index was assessed. GCF levels of MMP-1, MMP-8, TGF-β1, PDGF-AB, and VEGF were analyzed by enzyme-linked immunosorbent assay. Results: No significant differences were observed in the distribution of demographic data between study groups. GCF total amount of PDGF-AB was significantly lower in smokers compared to nonsmokers (P = 0.014). Total amount of GCF MMP-1, MMP-8, TGF-β1, and VEGF levels were similar in both study groups (P = 0.022). Conclusion: Smoking has the effect of decreasing GCF PDGF-AB while it does not affect GCF MMP-1, MMP-8, TGF-β1, and VEGF in periodontally healthy subjects. Since increased levels of these molecules are involved in periodontal breakdown, our findings may emphasize the importance for maintenance of periodontal health in smokers. © TÜBİTAK.Item Antifibrogenic role of valproic acid in streptozotocin induced diabetic rat penis(Blackwell Publishing Ltd, 2016) Kutlu O.; Karaguzel E.; Gurgen S.G.; Okatan A.E.; Kutlu S.; Bayraktar C.; Kazaz I.O.; Eren H.We investigated the therapeutic effects of valproic acid (VPA) on erectile dysfunction and reducing penile fibrosis in streptozocin (STZ)-induced diabetic rats. Eighteen male rats were divided into three experimental groups (Control, STZ-DM, STZ-DM plus VPA) and diabetes was induced by transperitoneal single dose STZ. Eight weeks after, VPA and placebo treatments were given according to groups for 15 days. All rats were anesthetised for the measurement of in vivo erectile response to cavernous nerve stimulation. Afterward penes were evaluated histologically in terms of immune labelling scores of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1). Slides were also evaluated in terms of collagen/smooth muscle ratio and penile apoptosis. After the treatment with VPA, erectile responses were found as improved when compared with STZ-DM rats but not statistically meaningful. eNOS and VEGF immune expressions diminished in penile corpora of STZ-DM rats and improved with VPA treatment. VPA led to decrease in TGF-β1 expression and collagen content of diabetic rats' penes. Penile apoptosis was not diminished with VPA. In conclusion, VPA treatment seems to be effective for reducing penile fibrosis in diabetic rats and more prolonged treatment period may enhance erectile functions. © 2016 Blackwell Verlag GmbH.Item Role of a combination dietary supplement containing mucopolysaccharides, vitamin C, and collagen on tendon healing in rats(Turkish Association of Orthopaedics and Traumatology, 2018) Gemalmaz H.C.; Sarıyılmaz K.; Ozkunt O.; Gurgen S.G.; Silay S.Objective: The aim of this study was to investigate the effect of mucopolysaccharide, vitamin C, and collagen supplementation on the healing of Achilles tendon in rats. Methods: Sixteen rats were separated into 2 groups. Both Achilles tendons of all rats were transected 5 mm above the insertion and repaired using a Kessler suture. After the surgical repair, the study group received the daily recommended amount of the supplement by gastric gavage, while the control group received a placebo. At the end of the third week, the animals were sacrificed. The biomechanical properties of the groups were compared with ultimate tensile strength and stiffness tests. The biological properties of the 2 groups were assessed with a histomorphometric comparison to determine the amount of collagen type I (COL1), proliferating cell nuclear antigen (PCNA), and transforming growth factor β1 (TGF-β1) expression in 3 different tissue subgroups (collagen matrix, tenocytes, and endotenon fibroblasts). Results: Analysis of histomorphometric results revealed that the rats receiving dietary supplements demonstrated a significant increase in PCNA (mean value of 86 in the control group and 168.85 in the trial group; p < 0.05) and TGF-β1 (mean value of 87.57 in the control group and 161.85 in the trial group; p < 0.05) in the endotenon fibroblasts of the repair site. However, there was no difference between the groups in PCNA or TGF-β1 when the collagen matrix and the tenocytes of the repair site were examined. Furthermore, no significant difference could be found between groups in COL1 in any of the 3 tissue subgroups (collagen matrix, tenocytes, and endotenon fibroblasts). The statistical analysis also indicated that the rats receiving supplements did not demonstrate a significant increase in the ultimate tendon tensile strength or stiffness. Conclusion: The results of this study revealed no advantage to the oral administration of the trial supplement in collagen synthesis or biomechanical properties in rats after 3 weeks using the presented study design. However, the increased expression of PCNA and TGFβ1 seen in the endotenon fibroblasts of the repair site might play a role in the continuum of tendon healing. © 2018 Turkish Association of Orthopaedics and TraumatologyItem Mesenchymal Stem Cells: a Potential Treatment Approach for Refractory Chronic Spontaneous Urticaria(Springer, 2021) Özgül Özdemir R.B.; Özdemir A.T.; Kırmaz C.; Ovalı E.; Ölmez E.; Kerem H.; Evrenos M.K.; Deniz G.The etiopathogenesis of chronic spontaneous urticaria (CSU) is not fully elucidated, and almost 30–40% of patients are resistant to treatments; therefore, there is still a need for the development of new and effective treatments. This study aimed to develop experimental cellular therapy for CSU patients resistant to current treatment options. Autologous adipose tissue mesenchymal stem cells (MSC) were administered to 10 refractory CSU patients who were then followed up for six months. The efficacy of treatment was evaluated according to the weekly urticaria activity scores (UAS7) and drug use scores (DUS7). To observe the effect of treatment on immune cells, CD4+ T cell subsets were analyzed by flow cytometry, and the serum IFN-γ, TNF-α, IL2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17a, IL-21, IL-22, TGF-β1, PGE2, IDO and anti-FcεRI levels were measured using the Luminex and ELISA methods. The values obtained were compared with 10 control refractory CSU patients and five healthy controls. We found that the T cell subsets and inflammatory molecules were not affected by MSC treatment during the follow-up period. In control patients, a significant decrease was detected only at the Th2 subset, TGF-β1, PGE2, IDO and anti-FcεRI levels on the 14th day of treatment. The UAS7 and DUS7 values of the MSC-treated patients significantly decreased during the follow-up period, but in control patients, a significant but temporary decrease was seen. According to our findings, unlike conventional treatment, MSC therapy resulted in longer and more effective recovery. Our data indicate that MSCs may be an alternative and effective approach for treatment-resistant CSU patients. [Figure not available: see fulltext.] © 2020, Springer Science+Business Media, LLC, part of Springer Nature.