Goal: 03 - Sağlık ve Kaliteli Yaşam
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AMAÇ 3: SAĞLIKLI BİREYLER
Çocuk ölüm oranlarının azaltılması, anne sağlığının iyileştirilmesi, HIV/AIDS, sıtma ve diğer hastalıklar ile mücadelede büyük aşama kaydetmiş durumdayız. 1990 yılından bu yana, önlenebilir çocuk ölümlerinde dünya genelinde %50’yi aşan azalma olmuştur. Anne ölümleri de dünya genelinde %45 azalmıştır. 2000 ile 2013 arasında HIV/AIDS bulaşma oranı %30 azalmış, 6,2 milyonu aşkın insan sıtmadan kurtarılmıştır.
Bu ölümler; önleme ve tedavi, eğitim, aşı kampanyaları, cinsel ve üreme sağlığı hizmetleri vasıtasıyla önlenebilir. Sürdürülebilir Kalkınma Amaçları; AIDS, verem, sıtma ve diğer bulaşıcı hastalık salgınlarını 2030 yılına kadar ortadan kaldırmaya yönelik cesur bir taahhüttür. Amaç, herkesin genel sağlık hizmeti, güvenli ve erişilebilir ilaç ve aşıya kavuşmasını sağlamaktır. Aşı araştırma ve geliştirmelerinin desteklenmesi, bu sürecin vazgeçilmez bir parçasıdır.
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Publication Metadata only NF-?B Inhibition Activity of Curcumin-Loaded Sterically Stabilized Micelles and Its Up-Regulator Effect on Enhancement of Cytotoxicity of a New Nano-Pirarubicin Formulation in the Treatment of Breast Cancer(2019-01-01) Eskandari, Zahra; BAHADORİ, FATEMEH; Altikatoglu, Melda; YENİGÜN, VİLDAN BETÜL; KOÇYİĞİT, ABDÜRRAHİM; Onyuksel, Hayat; KOÇYİĞİT, ABDÜRRAHİMPublication Open Access Serum obestatin and omentin levels in patients with diabetic nephropathy(2017-02-01) ZORLU, MEHMET; KISKAC, MUHARREM; Gueler, ERAY METİN; GUELTEPE, I.; YAVUZ, E.; CELIK, K.; KOCYIGIT, ABDÜRRAHİM; ZORLU, MEHMET; KISKAÇ, MUHARREM; GÜLER, ERAY METİN; KOÇYİĞİT, ABDÜRRAHİMIntroduction: Diabetic nephropathy is the leading cause of chronic kidney disease and accounts for almost 45% of all new patients requiring renal replacement therapy. Omentin and obestatin, two novel proteins were suggested to be associated with insulin resistance, type 2 diabetes and cardiovascular risk factors. Thus, we postulated that they may also have an association with diabetic nephropathy which is known to be an independent cardiovascular risk factor. In order to investigate such an association we compared serum omentin and obestatin levels in type 2 diabetic patients with normoalbuminuria (NA) and macroalbuminuria (MA). Materials and Methods: A total of 81 type 2 diabetic patients were separated into two groups according to their proteinuria status; patients with NA (n = 39) and patients with MA (n = 42). Two groups were compared in terms of serum omentin and obestatin levels. Results: While serum omentin levels did not differ among two groups (P = 0.407), serum obestatin levels were significantly higher in MA group (P = 0.001). Conclusion: The results of this study showed that higher serum levels of obestatin were associated with macro albuminuria suggesting that obestatin may have a role in underlying pathogenic mechanisms that leads to diabetic nephropathyPublication Metadata only Thymoquinone Enhances the Effect of Gamma Knife in B16-F10 Melanoma Through Inhibition of Phosphorylated STAT3(2019-01-01) HATİBOĞLU, MUSTAFA AZİZ; KOÇYİĞİT, ABDÜRRAHİM; GÜLER, ERAY METİN; Akdur, Kerime; Khan, Imran; Nalli, Arife; Karataş, Ersin; TÜZGEN, SAFFET; HATİBOĞLU, MUSTAFA AZİZ; KOÇYİĞİT, ABDÜRRAHİM; GÜLER, ERAY METİN; KHAN, IMRANBACKGROUND: Patients with brain metastasis from melanoma have a dismal prognosis with poor survival time. Gamma Knife (GK) is an effective treatment to control brain metastasis from melanoma. Thymoquinone (TQ) has emerged as a potential therapeutic option due to its antiproliferative effects on various cancers. The purpose of the study was to assess the effect of GK on B16-F10 melanoma cells in vitro and intracerebral melanoma in vivo, and its synergistic effect in combination with TQ.Publication Open Access The Importance of Polyphenols as Functional Food in Health(2019-04-01T00:00:00Z) GÜNEŞ BAYIR, Ayşe; Aksoy, Ayse Nur; KOÇYİĞİT, ABDÜRRAHİM; GÜNEŞ BAYIR, AYŞE; KOÇYİĞİT, ABDÜRRAHİMPolyphenols which are produced by plants are very important functional foods in our nutrition. Because of their diverse chemical structures, they are subject to main classification among them. The main groups of polyphenols are; flavanoids, lignans, stilbenes and phenolic acids. At the present time, the health effects of them have been investigated in several in vivo and in vitro studies. In addition to their antioxidant effects, they are known to have a pro-oxidant character. Polyphenols have important effects in protecting the body against external factors and the cleansing of reactive oxygen species which occur as a consequence of some diseases. Furthermore, polyphenols have effects on protection from specific diseases and stop their progression with certain mechanisms. In this review, various effects of polyphenols including antioxidant, pro-oxidant, cytotoxic, anti-inflammatory, antihypertensive, anti-diabetic are discussed which obtained from in vitro, in vivo experimental animal and clinical investigations.Publication Metadata only Intracellular pH-mediated induction of apoptosis in HeLa cells by a sulfonamide carbonic anhydrase inhibitor(2022-03-15T00:00:00Z) Koyuncu, Ismail; Temiz, Ebru; Durgun, Mustafa; KOÇYİĞİT, ABDÜRRAHİM; Yuksekdag, Ozgur; Supuran, Claudiu T.; KOÇYİĞİT, ABDÜRRAHİM© 2021Carbonic anhydrase IX (CAIX) is a hypoxia-associated transmembrane protein that is critical in the survival of cells. Because CAIX has a key role in pH regulation, its therapeutic effects have been heavily studied by different research laboratories. This study aims to investigate how a synthetic CAIX inhibitor triggers apoptosis in a cancer cell line, HeLa. In this regard, we investigated the effects of the compound I, synthesized as a CAIX inhibitor, on the survival of cancer cells. The compound I inhibited the proliferation of the CAIX+ HeLa cells, kept the cells in G0/G1 phase (74.7%) and altered the cells morphologies (AO/EtBr staining) and the nuclear structure (γ-H2AX staining). CAIX inhibition triggered apoptosis in HeLa cells with a rate of 47.4%. According to the expression of mediator genes (CASP-3, -8, -9, BAX, BCL-2, BECLIN, LC3), the both death pathways were activated in HeLa cells with the inhibition of CAIX with the compound I. The compound I was also determined to affect the genes and proteins that have a critical role in the regulation of apoptotic pathways (pro casp-3, cleaved casp-3, -8, -9, cleaved PARP and CAIX). Furthermore, CAIX inhibition caused changes in pH balance, disruption in organelle integrity of mitochondria, and increase intracellular reactive oxygen level of HeLa cells. Taken together, our findings suggest that CAIX inhibition has a potential in cancer treatment, and the compound I, a CAIX inhibitor, could be a promising therapeutic strategy in the treatment of aggressive tumours.Publication Metadata only Levan enhanced the NF-κB suppression activity of an oral nano PLGA-curcumin formulation in breast cancer treatment.(2021-08-19T00:00:00Z) Eskandari, Zahra; Bahadori, Fatemeh; Yenigun, Vildan Betül; Demiray, Mutlu; Eroğlu, Mehmet Sayip; Kocyigit, Abdurrahim; Oner, Ebru Toksoy; YENİGÜN, VILDAN BETÜL; KOÇYİĞİT, ABDÜRRAHİMPublication Metadata only Mononuclear leukocyte DNA damage and oxidative stress: The association with smoking of hand-rolled and filter-cigarettes(2011-04-03T00:00:00Z) Kocyigit, ABDÜRRAHİM; Selek, ŞAHBETTİN; Celik, Hakim; Dikilitas, Murat; KOÇYİĞİT, ABDÜRRAHİM; SELEK, ŞAHABETTİNCigarette smoking is a major cause of human cancer at various sites, although its carcinogenic mechanisms still remain unestablished. Based on the use of a filter, cigarette smoke can be divided into a gas phase and a tar phase. Both contain different concentrations of oxidants, free radicals and tobacco-specific carcinogens. To explore the effects of both filtered and non-filtered cigarette smoke on DNA damage and oxidative status, we measured the level of mononuclear leukocyte DNA damage by use of the single-cell gel electrophoresis (Comet) assay. We also determined malondialdehyde (MDA), protein carbonyl content (PC) and total antioxidative capacity (TAC) levels in blood plasma of smokers of manufactured filter-cigarettes and of hand-rolled cigarettes. Cotinine levels were also measured in plasma to estimate the degree of smoking. Mononuclear leukocyte DNA damage, plasma MDA, plasma PC and plasma cotinine levels were found significantly higher, while plasma TAC levels were found significantly lower in smokers of filter-cigarettes and smokers of hand-rolled cigarettes, compared with control subjects. TAC levels in hand-rolled and manufactured filter-cigarette smokers were not significantly different from each other. However, the levels of DNA damage. plasma MDA, plasma cotinine, and plasma protein oxidation were significantly higher in hand-rolled cigarette smokers than in filter-cigarette smokers. There was a significant positive correlation between MDA and DNA damage in both hand-rolled cigarette smokers and manufactured filter-cigarette smokers. This study indicates that smoking of hand-rolled cigarettes has stronger genotoxic and oxidative effects on the metabolism than smoking of manufactured filter-cigarettes. We propose that these harmful effects could be attributed to the higher level of oxidants. (C) 2011 Elsevier B.V. All rights reserved.Publication Open Access Selective inhibition of carbonic anhydrase-IX by sulphonamide derivatives induces pH and reactive oxygen species-mediated apoptosis in cervical cancer HeLa cells(2018-12-01) Koyuncu, Ismail; Gonel, Ataman; KOÇYİĞİT, ABDÜRRAHİM; Temiz, Ebru; Durgun, Mustafa; Supuran, Claudiu T.; KOÇYİĞİT, ABDÜRRAHİMSelective inhibition with sulphonamides of carbonic anhydrase (CA) IX reduces cell proliferation and induces apoptosis in human cancer cells. The effect on CA IX expression of seven previously synthesised sulphonamide inhibitors, with high affinity for CA IX, as well as their effect on the proliferation/apoptosis of cancer/normal cell lines was investigated. Two normal and three human cancer cell lines were used. Treatment resulted in dose- and time-dependent inhibition of the growth of various cancer cell lines. One compound showed remarkably high toxicity towards CA IX-positive HeLa cells. The mechanisms of apoptosis induction were determined with Annexin-V and AO/EB staining, cleaved caspases (caspase-3, caspase8, caspase-9) and cleaved PARP activation, reactive oxygen species production (ROS), mitochondrial membrane potential (MMP), intracellular pH (pHi), extracellular pH (pHe), lactate level and cell cycle analysis. The autophagy induction mechanisms were also investigated. The modulation of apoptotic and autophagic genes (Bax, Bcl-2, caspase-3, caspase-8, caspase-9, caspase-12, Beclin and LC3) was measured using real time PCR. The positive staining using c-H2AX and AO/EB dye, showed increased cleaved caspase-3, caspase-8, caspase-9, increased ROS production, MMP and enhanced mRNA expression of apoptotic genes, suggesting that anticancer effects are also exerted through its apoptosis-inducing properties. Our results show that such sulphonamides might have the potential as new leads for detailed investigations against CA IX-positive cervical cancers.Publication Open Access Inhibition of Carbonic Anhydrase IX Promotes Apoptosis through Intracellular pH Level Alterations in Cervical Cancer Cells(2021-06-01T00:00:00Z) Temiz, Ebru; Koyuncu, Ismail; Durgun, Mustafa; Caglayan, Murat; Gonel, Ataman; Güler, Eray Metin; KOÇYİĞİT, ABDÜRRAHİM; Supuran, Claudiu T.; KOÇYİĞİT, ABDÜRRAHİMCarbonic anhydrase IX (CAIX) is a hypoxia-related protein that plays a role in proliferation in solid tumours. However, how CAIX increases proliferation and metastasis in solid tumours is unclear. The objective of this study was to investigate how a synthetic CAIX inhibitor triggers apoptosis in the HeLa cell line. The intracellular effects of CAIX inhibition were determined with AO/EB, AnnexinV-PI, and γ-H2AX staining; measurements of intracellular pH (pHi), reactive oxygen species (ROS), and mitochondrial membrane potential (MMP); and analyses of cell cycle, apoptotic, and autophagic modulator gene expression (Bax, Bcl-2, caspase-3, caspase-8, caspase-9, caspase-12, Beclin, and LC3), caspase protein level (pro-caspase 3 and cleaved caspase-3, -8, -9), cleaved PARP activation, and CAIX protein level. Sulphonamide CAIX inhibitor E showed the lowest IC50 and the highest selectivity index in CAIX-positive HeLa cells. CAIX inhibition changed the morphology of HeLa cells and increased the ratio of apoptotic cells, dramatically disturbing the homeostasis of intracellular pHi, MMP and ROS levels. All these phenomena consequent to CA IX inhibition triggered apoptosis and autophagy in HeLa cells. Taken together, these results further endorse the previous findings that CAIX inhibitors represent an important therapeutic strategy, which is worth pursuing in different cancer types, considering that presently only one sulphonamide inhibitor, SLC-0111, has arrived in Phase Ib/II clinical trials as an antitumour/antimetastatic drug.Publication Metadata only Lecithin-acrylamido-2-methylpropane sulfonate based crosslinked phospholipid nanoparticles as drug carrier(2016-11-10) Mutlu, Esra Cansever; Bostan, Muge Sennaroglu; Bahadori, FATEMEH; Kocyigit, ABDÜRRAHİM; Oner, Ebru Toksoy; EROĞLU, MEHMET SAYIP; BAHADORİ, FATEMEH; KOÇYİĞİT, ABDÜRRAHİMIn this study, a novel paclitaxel (PTX) loaded and a crosslinked solid phospholipid nanoparticles (SLN-PTX) with negative surface charge was prepared by UV polymerization for drug delivery. Capping of positive charge of zwitterionic lecithin with negative charge of sodium 2-acrylamido-2-methyl-1-propanesulfonate (AMPS-Na) through cation exchange interaction produced a lecithin-AMPS (L-AMPS) complex. The amphiphilic and negative charged lipid complex was emulsified in the presence of emulsifier, paclitaxel, initiator, and methacrylated poly epsilon-caprolacton-diol (PCL-MAC) as a spacer. The colloidal system was subjected to UV-irradiation to obtain crosslinked nanoparticles. Completion of the UV-polymerization was monitored with differential scanning calorimetry (DSC), which indicated the disappearance of exothermic peaks of vinyl groups. The nanoparticle system, having an average size of 200 nm, exhibited high drug encapsulation (96%) with negatively charged surface (zeta potential had an average of -70 mV). PTX release profiles of the crosslinked and uncrosslinked SLN-PTXs were studied and their pharmacological properties were compared. The crosslinked nanoparticles exhibited more controlled release behavior with longer release time compared to the uncrosslinked ones. In vitro cytotoxicity test was conducted on MCF-7 human breast adenocarcinoma cell line, which indicated that the crosslinked SLN-PTXs have a potential therapeutic effect for breast cancer treatments. (c) 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 44105.