Investıgatıon Of Cell Death Mechanısms In Agıng Process

Bu çalışma yaşlanma sürecinde izlenen hücre ölüm mekanizmalarının araştırılması ve ayrıca anti-apoptotik ve anti-oksidan etkili melatonin ve curcuminin bu sürece etkilerinin gösterilmesi amacıyla planlandı. Çalışmamızda, melatonin (10 mg/kg/gün, sc), curcumin (30 mg/kg/gün, ip) ve salermide (100&#956;mol/&#956;l/gün, ip) uygulamalarının genç ve yaşlı sıçanların beyninde oksidatif stres, SIRT2, FOXO3a ekspresyonu ve apoptotik aktivite (BCL-2, BAX, BCL-2/BAX oranı ve BIM) üzerine etkisi araştırıldı. Bu amaçla, toplam 48 adet (3 aylık genç, n=24; 22 aylık yaşlı n=24) Wistar albino cinsi sıçan kullanılarak 8 grup oluşturuldu. Kontrol ve deney gruplarının enjeksiyonları 21 gün boyunca sürdürüldü. Beyinde serebral korteks ve hipokampus dokuları izole edildi. Total oksidan seviye (TOS) ve total antioksidan seviye (TAS) ölçümleri yapıldı ve oksidatif stres indeksi (OSI) hesaplandı. SIRT2, FOXO3a, BCL-2, BAX ve BIM ekspresyonları Western blotlama ile gösterildi. Ayrıca SIRT2 ve FOXO3a için sandviç ELISA yöntemi ile protein ölçümü yapıldı. İstatistiksel analiz için Two-way ANOVA, Pearson r si kullanıldı (p<0,05). Bulgularımız yaşlanmanın her iki beyin bölgesinde SIRT2, FOXO3a, TOS, OSI yi arttırdığını, BCL-2, BCL-2/BAX oranı ve TAS' ı ise azalttığını gösterdi. Ayrıca yaşlanmanın serebral kortekste BIM i, hipokampusta ise BAX' ı arttırdığı görüldü. Melatonin, curcumin ve salermide uygulamaları, etkileri beyinde bölge spesifik olmak üzere, yaşlanmaya bağlı görülen değişiklikleri tersine çevirmede etkili bulundu (p<0,05). Sonuç olarak, yaşlanmada eksojen melatonin ve curcumin uygulamaları, beyinde oksidatif stres ve apoptotik aktiviteyi baskılayarak nöral kayıpları engelleyebilir.The aim of this study was to investigate the cell death mechanisms in the aging process and to demonstrate the effects of anti-apoptotic and anti-oxidant melatonin and curcumin in this process. In the current study, we investigated the effects of melatonin (10 mg/kg/day, sc), curcumin (30 mg/kg/day, ip), and salermide (100&#956;mol/&#956;l/day, ip) treatments on oxidative stress parameters, SIRT2, FOXO3a expression levels and apoptotic activity in the young and aged rat brain. In this respect, a total of 48 male Wistar-albino rats (24 young rats, 3 months-old; 24 aged rats, 22 months-old) divided into 8 groups. The injections of the control and treatment groups were maintained for 21 days. Brain tissues were sampled from the cerebral cortex and hippocampus. Total oxidant status (TOS) and total antioxidant status (TAS) were measured. Oxidative stress index (OSI), was also calculated. SIRT2, FOXO3a, BCL-2, BAX and BIM expressions were tested by Western blotting. SIRT2 and FOXO3a protein levels was also measured by a sandwich ELISA method. Two-way ANOVA, Pearson s r were used for statistical analysis (p<0.05). Our findings showed that aging increased SIRT2, FOXO3a, TOS, OSI, and decreased BCL-2, BCL-2/BAX ratio and TAS in both brain regions. Aging also increased BIM in the cerebral cortex and BAX in the hippocampus. Melatonin, curcumin and salermide treatments reversed the age-related changes in the brain, while their effects are region specific. In sum, exogenous melatonin and curcumin treatments in aging can inhibit neural losses by suppressing oxidative stress and apoptotic activity in the brain

The relationship between oxidative stress and bcl-2 in hippocampus of older rats

Yaşlanmada çeşitli dokularda radikal yapımı artarken, antioksidan kapasitede azalma görülür. Bu durum hipokampusta dahil beynin farklı bölgelerinde gözlenen nörodejeneratif hastalıklarla birliktedir. Güçlü bir radikal süpürücü olarak bilinen melatonin yaşlanmada azalır. Curcumin ise oldukça güçlü antinflamatuar, antiproliferatif ve antioksidan özellikleri olan bir polifenoldür. Hücresel redoks dengenin sağlanmasında rol oynayan bcl-2?nin de antioksidan ve antiapoptotik özellikleri tanımlanmıştır. Çalışmamızda orta yaşlı sıçanlarda melatonin ve curcumin uygulamasının hipokampus dokusunda oksidatif stresin göstergesi MDA, antioksidan sistem göstergesi olarak fonksiyon gören GSH ve hücresel redoks düzenleyici bcl-2 düzeylerini nasıl etkilediğini araştırdık. Bu amaçla, MDA tayini için TBARS, GSH için modifiye Ellman, bcl-2 düzeyinin belirlenmesi için de western blot yöntemi kullanıldı. Etik kurul onayını takiben Wistar sıçanlardan laboratuvar şartları altında 12 saat aydınlık- karanlık siklusunda kalacak şekilde 5 grup oluşturuldu (13 aylık, n=30). Kontrol grubu (%1 etanol-PBS sc, saat 17:00?de, 30 gün), dimetilsülfoksit grubu (DMSO 100?l/bw ip, saat 17:00?de, 30gün), melatonin (MEL) grubu (10mg/kg+etanol-PBS sc, saat 17:00`de, 30 gün), Curcumin (CUR) (30mg/kg+DMSO ip, saat 17:00?de, 30 gün) ve MEL+CUR grubu. MEL, CUR ve MEL+CUR çalışma gruplarında hipokampus doku MDA düzeyleri PBS kontrol grubuna göre anlamlı olarak azalırken (p<0,05); CUR ve MEL+CUR gruplarındaki hipokampus doku GSH düzeylerinin PBS ve DMSO kontrol gruplarına kıyasla anlamlı olarak arttığı bulundu (p<0,05). Ayrıca; CUR ve MEL+CUR uygulaması yapılan her iki grupta da MDA ve GSH düzeyleri arasında negatif koreleasyon bulundu (sırasıyla r(6)= - 0,74; p=0,05 ve r(6)= - 0,78; p<0,05). CUR, MEL+CUR ve DMSO uygulaması yapılan gruplar, PBS kontrol grubu ve MEL uygulaması yapılan çalışma grubuyla karşılaştırıldığında hipokampal bcl2/beta aktin oranının anlamlı olarak azaldığı bulundu (p<0,05). Sonuç olarak, melatonin uygulaması radikal hasar düzeyini anlamlı düzeyde azaltırken, curcumin, curcumin ve melatoninin birlikte uygulanması radikal hasar düzeyini azaltmakla beraber GSH düzeyini de arttırmıştır. Ayrıca; Curcumin, curcumin ve melatoninin birlikte uygulanması bcl-2 düzeylerini de azaltmıştır. Dolayısıyla melatonin ve curcumin gibi antioksidanların orta yaşlardan itibaren kullanılması, yaşlanma sürecinden en çok etkilenen hipokampus gibi nöral yapıları nörodejeneratif hasarlara karşı korumada etkili olabilir.In aging process, the production of radicals in several tissues increases while antioxidant capacity reduces. This fact is observed in neurodegenerative diseases in various brain regions including hippocampus. Melatonin, which is known as a powerful scavenger of radicals, significantly decreases with aging. Curcumin is a polyphenol which has anti-inflammatory, antiproliferative and antioxidant effects. Bcl- 2, which takes a role in regulation of cellular redox state, is identified with antioxidant and antiapoptotic features. The aim of the present study was to investigate the impact of melatonin and curcumin treatments on MDA which is an oxidative stress indicator; GSH, which function as an antioxidant system indicator; and bcl- 2 which is a regulator of cellular redox status. In this respect, MDA, GSH and bcl-2 was assessed by using TBARS, modified Ellman and Western Blott techniques, respectively. Following the approval of the ethical committee, Wistar rats divided 5 groups (13 month-aged, n=30) and they were housed under laboratory conditions with 12 h-light/dark cycle. These groups were control group (1% ethanol-PBS sc, at 17:00, for 30 days), dimethyl sulfoxide (DMSO 100?l/bw ip, at 17:00, for 30 days), melatonin (MEL-10mg/kg+ethanol-PBS sc, at 17:00, for 30 days), curcumin (CUR- 30mg/kg+DMSO ip, at 17:00, for 30 days) and MEL+CUR.88 Comparing to the PBS-control group, MDA levels in hippocampus significantly decreased in treatment groups of MEL, CUR, MEL+CUR (p<0,05). Furthermore, the level of GSH increased in CUR and MEL+CUR groups, compared to PBS and DMSO groups (p<0,05). MDA and GSH were negatively correlated in CUR and MEL+CUR groups (r(6)= -0,74; p=0,05 ve r(6)= -0,78; p<0,05, respectively). Bcl2/beta actin ratio significantly decreased in CUR, MEL+CUR and DMSO groups, compared to PBS and MEL groups (p<0,05). In sum, findings indicated that the treatment of melatonin alone decreased radical damage in hippocampus. However, the treatment of curcumin alone and of curcumin and melatonin together not only decreased the radical damage, but they also increased GSH level in hippocampus. Furthermore, the treatment of curcumin alone and of curcumin and melatonin together decreased bcl-2 level. Consequently, the treatment of the antioxidants such as melatonin and curcumin in adulthood might be an effective protector against neurodegenerative damages in hippocampus through the aging process

Sedanter Kadın ve Erkekerde Beden Kitle İndeksi ile Pes Planus, Denge, Yaşam Kalitesi ve Ağrı Düzeyleri Arasındaki İlişki

Amaç: Bu çalışmanın amacı sedanter erkek ve kadınlarda beden kitle indeksi ile pes planus, denge, yaşam kalitesi ve ağrı arasındaki ilişkinin araştırılmasıdır. Gereç ve Yöntemler: Çalışmamıza 18-30 yaş aralığında, toplam 82 sedanter gönüllü (39 erkek, 43 kadın) katıldı. Katılımcıların fiziksel aktivite düzeyleri Uluslararası Fiziksel Aktivite Ölçeği ile değerlendirildi ve beden kitle indeksleri hesaplandı. Her iki ayak için pes planus değerlendirmesi Naviküler Düşme Testi (NDT) ile yapıldı. Statik denge ölçümü Tek Ayak Üstünde Durma testi ile, dinamik denge ölçümü ise Dört Adım Kare ve Zamanlı Kalk-Yürü testleri ile yapıldı. Yaşam kalitesinin değerlendirilmesinde Kısa Form-36 (SF-36) ölçeği kullanıldı, ağrı değerlendirmesi ise Vizuel Analog Skala (VAS) ile yapıldı.Bulgular: BKİ ile yaş, kilo, NDT, Dinamik Denge-Zamanlı Kalk ve Yürü test puanları arasında pozitif yönde; Statik Denge, SF-36-Fiziksel fonksiyon, SF-36-Genel sağlık puanları arasında ise negatif yönde ilişki saptandı. Erkeklerde boy, kilo ve BKİ’ nin yanı sıra NDT-sağ ayak ölçümü daha yüksek bulundu. NDT sınıflamasına göre yapılan gruplamada pes planusu olan katılımcıların kilo, BKİ ve VAS (şiddetli) ölçümlerinin daha yüksek olduğu, ayrıca statik ve dinamik dengelerinin daha kötü olduğu görüldü.Sonuç: Bulgularımız sedanter genç-erişkinlerde beden kitle indeksinin, pes planus, vücut dengesi ve yaşam kalitesi ile ilişkili olduğunu göstermekte, ayrıca pes planusun statik ve dinamik vücut dengesini olumsuz yönde etkilediğine işaret etmektedir

Protective effect of Apelin-13 in a cyclophosphamide-induced cardiorenal toxicity model in rats.

Cyclophosphamide is a chemotherapeutic drug that is widely used in the clinic and can cause multi-organ toxicity. Apelin-13 is an endogenous adipocytokine with antioxidant properties. Therefore, this study aimed to investigate the possibility of apelin-13 being a potential therapeutic agent on cardiac toxicity and nephrotoxicity caused by cyclophosphamide. In this study, a total of 4 groups were formed, including 8 rats in each group. Group 1: The control group was administered only saline (ip). Group 2: Cyclophosphamide, a single dose of 200 mg/kg (ip) on day 7. Group 3: Apelin-13 (15 μg/kg), for 7 days (ip). Group 4: Administering apelin-13 (15 μg/kg) (ip) for 7 days and a single dose of cyclophosphamide (200 mg/kg) (ip) on day 7, the rats were sacrificed on day 8. LDH, cTn1, cK-Mb, AST, ALT, ALP, MDA, creatinine, and BUN were found to be high in the cyclophosphamide group, however, these values were reduced with apelin-13 administration. Antioxidant enzymes such as SOD, GPx, CAT, and GSH decreased in the cyclophosphamide group, apelin-13 increased these enzyme activities. In addition, histopathological examinations also supported the results obtained. The findings of this study showed that apelin-13 has a protective effect against cardiorenal toxicity caused by cyclophosphamide.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

SIRT2 and FOXO3a expressions in the cerebral cortex and hippocampus of young and aged male rats: antioxidant and anti-apoptotic effects of melatonin

Melatonin has antioxidant, anti-apoptotic and anti-aging effects in the brain. Sirtuin2 (SIRT2) accumulates in the central nervous system with aging, and its inhibition appears to be protective in aging and aging-related neurodegenerative diseases. Forkhead Box-class O3a (FOXO3a) transcription factor is one of the main targets of SIRT2, and SIRT2-mediated FOXO3a deacetylation is closely related to aging, oxidative stress, and apoptosis. This study aimed to investigate the effects of melatonin on SIRT2 and FOXO3a expressions in the cerebral cortex and hippocampus of aged rats. Young (3 months, n = 18) and aged (22 months, n = 18) male Wistar rats were divided into control (4% DMSO-PBS, sc, for 21 days), melatonin (10 mg/kg, sc, for 21 days) and salermide (1 mM; 25 μl/100 g bw, ip, for 21 days) groups. SIRT2, FOXO3a, Bcl-2, Bax and Bim expressions in the cerebral cortex and hippocampus were demonstrated by Western blotting. SIRT2 and FOXO3a protein levels were also measured by a sandwich ELISA method. Oxidative stress index (OSI) was calculated by measuring total oxidant status (TOS) and total antioxidant status (TAS). Aging increased SIRT2, FOXO3a, Bim (only in the cerebral cortex), Bax (only in the hippocampus), TOS, and OSI, while decreasing Bcl-2, Bcl-2/Bax and TAS in both brain regions. Melatonin decreased SIRT2, FOXO3a, oxidative stress parameters and pro-apoptotic proteins, while increasing TAS, Bcl-2 and Bcl-2/Bax, more specifically in the hippocampus of the aged brain. Our results indicate that inhibition of SIRT2 and FOXO3a expressions appears to be involved in the protective effects of melatonin in the hippocampus of aged rats

Baculoviral vector loaded mesenchymal stem cells as efficient gene therapy tools for cancer treatment

Insufficient targeting of the therapeutic genes to tumor cells is one of the major reasons for failure in cancer gene therapy. Mesenchymal stem cells (MSCs) seem to be a good candidate as a carrier for gene therapy because of its selective tumor tissue-homing properties. In the current study, we constructed baculoviral vectors (BVs) carrying cytosine deaminase (CD) (BV-CD) or green fluorescence protein (GFP) genes (BV-GFP) and tested the transduction efficiency of the vectors in tumor and mesenchymal stem cells. We also tested the in vivo efficacy of the BV-CD vector in a colon cancer model. Our results showed that the recombinant baculoviral vectors can efficiently transduce mammalian cells and express genes of interest. The BV-CD vector treatment caused significant in vitro cytotoxicity when used with 5-fluorocytosine. MSCs loaded with the BV-CD vector caused a significant delay in tumor growth and increased survival when compared to control and MSC alone treated groups bearing colon cancer. Our results show that the recombinant BV-CD vector could be used either alone or loaded into MSCs in the treatment of established tumors

CoCoNet: Towards coast to coast networks of marine protected areas (From the shore to the high and deep sea), coupled with sea-based wind energy potential

This volume contains the main results of the EC FP7 "The Ocean of Tomorrow" Project CoCoNet, divided in two sections: 1) a set of guidelines to design networks of Marine Protected Areas in the Mediterranean and the Black Seas; 2) a smart wind chart that will allow evaluating the possibility of installing Offshore Wind Farms in both seas. The concept of Cells of Ecosystem Functioning, based on connectivity, is introduced to define natural units of management and conservation. The definition of Good Environmental Status, as defined in the Marine Strategy Framework Directive, is fully embraced to set the objectives of the project, by adopting a holistic approach that integrates a full set of disciplines, ranging from physics to bio-ecology, economics, engineering and many sub-disciplines. The CoCoNet Consortium involved scientist sfrom 22 states, based in Africa, Asia, and Europe, contributing to build a coherent scientific community

Editorial. A supplement of Scires-it on the COCONET european project

The Supplement to vol. 6, 2016 of SCIRES-IT contains the result of CoCoNet (Towards COast to COast NETworks of marine protected areas, coupled with sea-based wind energy potential), a project of the EU Oceans of Tomorrow programme (http://www.coconet-fp7.eu). The European Union requires Open Access to the results of the projects resulting from its support to scientific advancement. This is in full accordance with the policy of SCIRES-IT, an eco-sustainable open–access journal, which joins the main principles of the Berlin Declaration on Open Access with the aims of the International Convention on Biological Diversity. CoCoNet tackled two problems that are closely linked with each other: the protection of the marine environment and clean energy production. Hence, the Supplement is divided into two parts that, together, form a unicum