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The Canakkale Wars Gallipoli Historical Area (CWGHA) has national and international importance due to its historical and natural value. The area is rich in terms of its biodiversity, untouched coasts, archaeological sites, wetland. It has value as important natural and cultural resource potential for any type of tourism activity in the region. The aim of this study is to find out the potential of ecotourism, which might be one of the important means of conserving the natural and cultural resource assets of the CWGHA. For this purpose, the method of Ecotourism Opportunity Spectrum (ECOS) was applied to question the potential for ecotourism in rural areas. In this context, the potential of ecotourism and sustainable development of the area was questioned. According to the research results, there are not any residential unit which has the 'High' ecotourism opportunities. The five of the settlements (Kilitbahir, Alcitepe, Seddulbahir, Buyuk Anafarta, Kucuk Anafarta) were determined in terms of eco-tourism opportunities 'Moderate' grade, while Behramli, Kocadere and Bigali villages were 'Low' grade. These eight villages have an average potential for ecotourism activities. However, it is very clear that this potential can be applied considering the correct planning decisions and the balance of use - conservation. Various issues relating to the current state of the settlers were discussed. Also several recommendations were made based on protection to increase the ecotourism potential of these villages. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to give an overview of studies investigating the role of fludeoxyglucose F18 (F-FDG) positron emission tomography (PET) scanning in patients with aortic aneurysms with a focus on molecular characteristics of the aneurysm wall. Methods: MEDLINE, EMBASE, and the Cochrane database were searched for relevant articles. After inclusion and exclusion, we selected 18 relevant articles reporting on F-FDG PET scanning of aortic aneurysms. Results: The sample size of studies is limited, and there are no standardized imaging protocols and quantification methods. F-FDG PET scanning was shown to display molecular characteristics of the aortic wall. Different studies showed contradictory findings of aortic F-FDG uptake in aneurysm patients compared to controls. Conclusions: Non-invasively determining molecular characteristics of aortic wall weakening might lead to better rupture and growth prediction. This might influence the decision of the surgeon between conservative and surgical treatment of aneurysms. To date, there is conflicted evidence regarding the use of F-FDG PET scanning to predict aneurysm rupture and growth. The role of F-FDG PET scanning in rupture risk prediction needs to be further investigated, and standardized imaging protocols and quantification methods need to be implemented. [ABSTRACT FROM AUTHOR]

In this study; existed conditions, general features, planning principles and standarts of the sport areas in Çankırı provincial center were examined and physical efficiency of these areas were evaluated in terms of field, facility capacity, facility size, facility type, and facility number, also service areas. Service areas were determined by using Geographical Information System (GIS). The total areas of the sport areas in the provincial center were found as 161 decares, for accessing to planning standarts of sport area, it would be determined that needed 241 decares sport areas which has been 28 new sport facilities in the provincial center. As a result, according to planning criteria of sport areas, the sport areas in Çankırı provincial center were found insufficiently in terms of the facility type and number, facility capacity and size and service area and the number of sport area. In addition, it was determined that most of the existing sport areas were neglected by professional maintance and these areas were planned without any considerations with green areas. According to these result, accurate proposal were presented to be sufficient and successful in existing and future sport areas in the provincial center. [ABSTRACT FROM AUTHOR]

Objective: Since the joint microenvironment and tissue homeostasis are highly dependent on synovial fluid, we aimed to compare the essential chondrocyte signaling signatures of non-osteoarthritic vs end-stage osteoarthritic knee synovial fluid. Moreover, we determined the phenotypic consequence of the distinct signaling patterns on articular chondrocytes., Methods: Protein profiling of synovial fluid was performed using antibody arrays. Chondrocyte signaling and phenotypic changes induced by non-osteoarthritic and osteoarthritic synovial fluid were analyzed using a phospho-kinase array, luciferase-based transcription factor activity assays, and RT-qPCR. The origin of osteoarthritic synovial fluid signaling was evaluated by comparing the signaling responses of conditioned media from cartilage, synovium, infrapatellar fat pad and meniscus. Osteoarthritic synovial fluid induced pathway-phenotype relationships were evaluated using pharmacological inhibitors., Results: Compared to non-osteoarthritic synovial fluid, osteoarthritic synovial fluid was enriched in cytokines, chemokines and growth factors that provoked differential MAPK, AKT, NFκB and cell cycle signaling in chondrocytes. Functional pathway analysis confirmed increased activity of these signaling events upon osteoarthritic synovial fluid stimulation. Tissue secretomes of osteoarthritic cartilage, synovium, infrapatellar fat pad and meniscus activated several inflammatory signaling routes. Furthermore, the distinct pathway signatures of osteoarthritic synovial fluid led to accelerated chondrocyte dedifferentiation via MAPK/ERK signaling, increased chondrocyte fibrosis through MAPK/JNK and PI 3 K/AKT activation, an elevated inflammatory response mediated by cPKC/NFκB, production of extracellular matrix-degrading enzymes by MAPK/p38 and PI 3 K/AKT routes, and enabling of chondrocyte proliferation., Conclusion: This study provides the first mechanistic comparison between non-osteoarthritic and osteoarthritic synovial fluid, highlighting MAPKs, cPKC/NFκB and PI 3 K/AKT as crucial OA-associated intracellular signaling routes., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: For many proteins from osteoarthritic synovial fluid, their intra-articular tissue of origin remains unknown. In this study we performed comparative proteomics to identify osteoarthritis-specific and joint tissue-dependent secreted proteins that may serve as candidates for osteoarthritis biomarker development on a tissue-specific basis., Design: Protein secretomes of cartilage, synovium, Hoffa's fat pad and meniscus from knee osteoarthritis patients were determined using liquid chromatography tandem mass spectrometry, followed by label-free quantification. Validation of tissue-dependent protein species was conducted by ELISA on independent samples. Differential proteomes of osteoarthritic and non-osteoarthritic knee synovial fluids were obtained via similar proteomics approach, followed by ELISA validation., Results: Proteomics revealed 64 proteins highly secreted from cartilage, 94 from synovium, 37 from Hoffa's fat pad and 21 from meniscus. Proteomic analyses of osteoarthritic vs non-osteoarthritic knee synovial fluid revealed 70 proteins with a relatively higher abundance and 264 proteins with a relatively lower abundance in osteoarthritic synovial fluid. Of the 70 higher abundance proteins, 23 were amongst the most highly expressed in the secretomes of a specific intra-articular tissue measured. Tissue-dependent release was validated for SLPI, C8, CLU, FN1, RARRES2, MATN3, MMP3 and TNC. Abundance in synovial fluid of tissue-dependent proteins was validated for IGF2, AHSG, FN1, CFB, KNG and C8., Conclusions: We identified proteins with a tissue-dependent release from intra-articular human knee OA tissues. A number of these proteins also had an osteoarthritis-specific abundance in knee synovial fluid. These proteins may serve as novel candidates for osteoarthritis biomarker development on a tissue-specific basis., Competing Interests: Conflict of Interests TJM Welting is listed as inventor on patents: WO2017178251, WO2017178253 and US 20130123314. PJ Emans and LW van Rhijn are listed as inventors on patent US 20130123314. LW van Rhijn, PJ Emans and TJM Welting have shares in Chondropeptix and are CDO, CMO and CSO of Chondropeptix, respectively., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

During standard expansion culture (i.e., plasma osmolarity, 280 mOsm) human articular chondrocytes dedifferentiate, making them inappropriate for autologous chondrocyte implantation to treat cartilage defects. Increasing the osmolarity of culture media to physiological osmolarity levels of cartilage (i.e., 380 mOsm), increases collagen type II ( COL2A1 ) expression of human articular chondrocytes in vitro , but the underlying molecular mechanism is not fully understood. We hypothesized that TGF-β superfamily signaling may drive expression of COL2A1 under physiological osmolarity culture conditions. Human articular chondrocytes were cultured in cytokine-free medium of 280 or 380 mOsm with or without siRNA mediated TGF-β2 knockdown (RNAi). Expression of TGF-β isoforms, and collagen type II was evaluated by RT-qPCR and immunoblotting. TGF-β2 protein secretion was evaluated using ELISA and TGF-β bioactivity was determined using an established reporter assay. Involvement of BMP signaling was investigated by culturing human articular chondrocytes in the presence or absence of BMP inhibitor dorsomorphin and BMP bioactivity was determined using an established reporter assay. Physiological cartilage osmolarity (i.e., physosmolarity) most prominently increased TGF-β2 mRNA expression and protein secretion as well as TGF-β bioactivity. Upon TGF-β2 isoform-specific knockdown, gene expression of chondrocyte marker COL2A1 was induced. TGF-β2 RNAi under physosmolarity enhanced TGF-β bioactivity. BMP bioactivity increased upon physosmotic treatment, but was not related to TGF-β2 RNAi. In contrast, dorsomorphin inhibited COL2A1 mRNA expression in human articular chondrocytes independent of the osmotic condition. Our data suggest a role for TGF-β superfamily member signaling in physosmolarity-induced mRNA expression of collagen type II. As physosmotic conditions favor the expression of COL2A1 independent of our manipulations, contribution of other metabolic, post-transcriptional or epigenetic factors cannot be excluded in the underlying complex and interdependent regulation of marker gene expression. Dissecting these molecular mechanisms holds potential to further improve future cell-based chondral repair strategies.

Objective: The Hoffa's fat pad (HFP) is an intra-articular adipose tissue which is situated under and behind the patella. It contains immune cells next to adipocytes and secretes inflammatory factors during osteoarthritis (OA). In this study, we compared the release profile of prostanoids, which are involved in inflammation, of HFP from OA patients vs patients with a focal cartilage defect (CD) without evidence for OA on MRI and investigated the prostanoid modulatory anti-inflammatory action of celecoxib on HFP., Design: Prostanoid release was analyzed in conditioned medium of HFP explant cultures from 17 osteoarthritic patients and 12 CD patients, in the presence or absence of celecoxib. Furthermore, gene expression of COX enzymes and expression of genes indicative of a pro-inflammatory or anti-inflammatory phenotype of HFP was analyzed., Results: Prostanoid release by HFP from knee OA patients clustered in two subgroups with high and low prostanoid producers. HFP from high prostanoid producers released higher amounts of PGE 2 , PGF 2α and PGD 2 compared to HFP from CD patients. PGE 2 release by OA HFP was positively associated with expression of genes known to be expressed by M1 macrophages, indicating a role for macrophages. Celecoxib modulated prostanoid release by HFP, and also modulated the inflammation ratio towards a more favorable anti-inflammatory M2 phenotype, most effectively in patients with higher prostanoid release profiles., Conclusion: In knee OA patients with inflamed HFP's, celecoxib may exert positive effects in the knee joint via decreasing the release of prostanoids produced by the HFP and by favorably modulating the anti-inflammatory marker expression in HFP., (Copyright © 2018 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Culturing chondrocytes under oxygen tension closely resembling their in vivo environment has been shown to have positive effects on matrix synthesis. In redifferentiation of expanded chondrocytes, hypoxia increased collagen type II expression. However, the mechanism by which hypoxia enhances redifferentiation is still unknown. We employed novel bioreactor technology to investigate the role of TGF-β, a growth factor heavily implicated in matrix production, in chondrocytes under hypoxia. Dedifferentiated chondrocytes in alginate were cultured for 48h under hypoxic (1% pO2) or normoxic (20%) conditions, using specialized bioreactor technology. Hypoxia induced gene expression (GDF1-, PHD3, HAS2, VEGF, COX2), chondrocyte markers (SOX9, COL2, COL1, AGC1 and MMP13), as well as components of the TGF-β signaling pathway (TGF-β isoforms, receptors, and downstream effectors) were analyzed by qPCR after 48h. In addition, protein expression of COL2 and TGF-β2 were evaluated. To further elucidate the involvement of the TGF-β2, we used siRNA and ALK5 inhibition. Hypoxic culture showed robust upregulation of hypoxic markers as well as upregulation of SOX9 and COL2 expression. Of all TGF-β isoforms, only TGF-β2 was upregulated under hypoxia on both gene and protein level. In addition, both type I receptors (ALK1 and ALK5) were upregulated under hypoxia, but type II and III receptors were not. TGF-β2 downregulation via siRNA abrogated the hypoxia-induced COL2 expression, as did ALK5 inhibition, giving a strong indication that this pathway is involved in chondrocyte redifferentiation under low oxygen tension. Hypoxic culture is a common approach for cartilage tissue engineering, but its underlying mechanisms are still poorly understood. Here, we show that increased TGF-β2 signaling through ALK5 plays a role in hypoxia-induced redifferentiation of chondrocytes., (Copyright © 2014 Elsevier GmbH. All rights reserved.)