03 - Sağlık ve Kaliteli Yaşam

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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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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, ABDÜRRAHİM
Introduction: 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 nephropathy
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Handbook of Oxidative Stress in Cancer
(2022-01-01T00:00:00Z) Güler, Eray Metin; KOÇYİĞİT, ABDÜRRAHİM
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, ABDÜRRAHİM
Selective 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.
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, ABDÜRRAHİM
Carbonic 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.
Open Access
Circulating furin, IL-6, and presepsin levels and disease severity in SARS-CoV-2-infected patients
(2021-06-01T00:00:00Z) Kocyigit, Abdurrahim; Sogut, Ozgur; Kanimdan, Ebru; Guler, Eray Metin; Kaplan, Onur; Eren, Canan; Ozman, Zeynep; Yasar, Oznur; KOÇYİĞİT, ABDÜRRAHİM; BALKAN, EZGİ; KANIMDAN, EBRU; YENİGÜN, VILDAN BETÜL; ÖZMAN, ZEYNEP
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a vast number of infections and deaths that deeply affect the world. When the virus encounters the host cell, it binds to angiotensin-converting enzyme 2, then the S protein of the virus is broken down by the transmembrane protease serine 2 with the help of furin, allowing the virus to enter the cell. The elevated inflammatory cytokines suggest that a cytokine storm, also known as cytokine release syndrome, may play a major role in the pathology of COVID-19. Therefore, the aim of this study is to investigate the relationship between circulating furin levels, disease severity, and inflammation in patients with SARS-CoV-2. A total of 52 SARS-CoV-2 patients and 36 healthy control participants were included in this study. SARS- CoV-2 patients were scored by the disease activity score. Serum furin, presepsin, and interleukin-6 (IL-6) levels were assessed using an enzyme-linked immunosorbent assay. The mean furin, presepsin, and IL-6 levels were significantly higher in the peripheral blood of SARS-CoV-2 compared to the controls (p < 0.001). There were close positive relationship between serum furin and IL-6, furin and presepsin, and furin and disease severity (r = 0.793, p < 0001; r = 0.521, p < 0.001; and r = 0,533, p < 0.001, respectively) in patients with SARS-CoV-2. These results suggest that furin may contribute to the exacerbation of SARS-CoV-2 infection and increased inflammation, and could be used as a predictor of disease severity in COVID-19 patients.
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CUSCUTA CAMPESTRİS TEDAVİSİ İLE MİDE KANSERİ HÜCRELERİNDE APOPTOZUN İNDÜKLENMESİ VE REAKTİF OKSİJEN TÜRLERİNİN OLUŞUMU YOLUYLA PROLİFERASYONUN ENGELLENMESİ
(2021-08-01T00:00:00Z) Koçyiğit, Abdürrahim; KOÇYİĞİT, ABDÜRRAHİM; HACIOSMANOĞLU, EBRU
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\"PROPOLİSİN KOLOREKTAL KANSERDE 5-FLUOROURASİLİN ETKİNLİĞİNİ ARTIRMASI VE YAN ETKİLERİNİ DÜŞÜRMESİ ÜZERİNE OLAN IN VITRO VE IN VIVO BİR ÇALIŞMA\"
(2022-12-01) Balkan E.; Özman Z.; Koçyiğit A.; BALKAN, EZGİ; ÖZMAN, ZEYNEP; KOÇYİĞİT, ABDÜRRAHİM
Giriş ve amaç: Kolorektal kanser tedavisinde kullanılan geleneksel yöntemler yetersiz olduğundan alternatif tedavi arayışları devam etmektedir. Bu çalışma, 5-florourasil (5-FU) ve Anadolu propolis ekstraktının (PE) kombine tedavisinin CRC üzerindeki anti-tümör etkilerini ve etki mekanizmasını hem in vitro hem de in vivo çalışmalarla incelemeyi amaçlamaktadır. Deneysel prosedür: Lusiferaz ile transfekte edilmiş LoVo hücreleri (LoVo-Luc) ve sağlıklı kolon hücreleri (CCD-18Co), 24 saat boyunca 5-FU ve PE\"nin farklı konsantrasyonlarına ve bunların kombinasyonlarına maruz bırakıldı. İnkübasyondan sonra genotoksik, apoptotik sitotoksik etkiler ve hücre içi reaktif oksijen türleri (iROS) seviyeleri değerlendirildi. İn vivo anti-tümör etkilerini görselleştirmek için LoVo hücreleri, lusiferaz geni (LoVo-Luc) ile transfekte edildi ve çıplak farelerde kanser, kserografik olarak indüklendi. Tümör oluşumundan sonra, çıplak fareler PE, 5-FU ve bunların kombinasyonları ile tedavi edildi. Anti-tümör etkileri canlı hayvan görüntüleme sistemi, histopatolojik ve biyokimyasal yöntemlerle analiz edildi. Sonuçlar: İn vitro bulgular, PE\"nin LoVo ve CCD-18Co hücrelerinde 5-FU\"nun genotoksik, apoptotik ve sitotoksik etkilerini güçlendirdiğini ve bu aktivitelerin bu ajanın Iros oluşturucu etkileri ile ilişkili olduğunu gösterdi. Kanser hücreleri, özellikle daha yüksek dozlarda, bu kombinasyon tedavisine sağlıklı hücrelerden daha duyarlıydı. Fare ksenograft modelinden elde edilen in vivo veriler, PE'nin intraperitoneal (IP) uygulamasının, yan etkilerini azaltarak 5-FU'nun kolon CRC'sine karşı anti-tümör etkinliğini arttırdığını açıkça göstermiştir. IP uygulamasıyla karşılaştırıldığında, oral yoldan verilen PE'nin, büyük olasılıkla absorpsiyon başarısızlığına bağlı olarak daha az etkili olduğu gösterilmiştir. Sonuç: Sonuçlar, PE\"nin tümörde doza bağımlı bir şekilde iROS oluşturucu etki ile 5-FU'nun etkinliğini arttırırken yan etkileri azalttığını göstermektedir. Bu nedenle, CRC için ek tedavi olarak kabul edilebilir.
Open Access
Assessment of the antiproliferative and apoptotic roles of sulfonamide carbonic anhydrase IX inhibitors in HeLa cancer cell line
(2019-01-01T00:00:00Z) Koyuncu, Ismail; Gonel, Ataman; Durgun, Mustafa; KOÇYİĞİT, ABDÜRRAHİM; Yuksekdag, Ozgur; Supuran, Claudiu T.; KOÇYİĞİT, ABDÜRRAHİM
Carbonic anhydrase IX (CA IX) has recently been validated as an antitumor/antimetastatic drug target. In this study, we examined the underlying molecular mechanisms and the anticancer activity of sulfonamide CA IX inhibitors against cervical cancer cell lines. The effects of several sulfonamides on HeLa, MDA-MB231, HT-29 cancer cell lines, and normal cell lines (HEK-293, PNT-1A) viability were determined. The compounds showed high cytotoxic and apoptotic activities, mainly against HeLa cells overexpressing CA IX. We were also examined for intracellular reactive oxygen species (ROS) production; intra-/extracellular pH changes, for inhibition of cell proliferation, cellular mitochondrial membrane potential change and for the detection of caspase 3, 8, 9, and CA IX protein levels. Of the investigated sulfonamides, one compound was found to possess high cytotoxic and anti-proliferative effects in HeLa cells. The cytotoxic effect occurred via apoptosis, being accompanied by a return of pHe/pHi towards normal values as for other CA IX inhibitors investigated earlier.
Open Access
Cytotoxic, Apoptotic and Genotoxic Effects of Lipid-Based and Polymeric Nano Micelles, an In Vitro Evaluation
(2017-11-01) BAHADORİ, FATEMEH; KOÇYİĞİT, ABDÜRRAHİM; DAĞ, AYDAN; TOPÇU, GÜLAÇTI; BAHADORİ, FATEMEH; KOÇYİĞİT, ABDÜRRAHİM; DAĞ, AYDAN; TOPÇU, GÜLAÇTI
Self-assembly systems (SAS) mainly consist of micelles, and liposomes are the classes of Nano Drug Delivery Systems with superior properties compared to traditional therapeutics in targeting cancer tumors. All commercially available nano-formulations of chemotherapeutics currently consist of SAS. According to our knowledge, a specific toxicity comparison based on material differences has not yet been performed. The purpose of this study was to evaluate and compare the toxicity of two SAS consisting of Sterically Stabilized Micelles (SSM) made of a lipid-based amphiphilic distearoyl-sn-glycero-phosphatidylethanolamine-polyethylene glycol (PEG)-2000 and a polymeric micelle (PM) consisting of Y-shape amphiphilic block copolymer, synthesized using poly ε-caprolactone and PEG. The mechanism of cytotoxicity and genotoxicity of micelles on L-929 healthy mouse fibroblast cells was assessed using Sulforhodamine-B, WST-1, Acridine Orange/Ethidium Bromide and alkaline single-cell gel electrophoresis assays. Results showed that SSM in conc. of 40 mg/mL shows very low cytotoxicity at the end of 24, 48 and 72 h. The DNA damage caused by SSM was much lower than PM while the latter one showed significant toxicity by causing apoptosis with the ED50 value of 3 mg/mL. While the DNA damage caused by SSM was ignorable, some DNA chain breaks were detected on cells treated with PM.
Open Access
Investigation of dose-dependent effects of berberine against renal ischemia/reperfusion injury in experimental diabetic rats
(2019-01-01) Kanbay, Songül; KUMAŞ, MELTEM; EŞREFOĞLU, MUKADDES; Karataş, Ersin; Duymaç, Nurcihan; ERGÜN, İLYAS SAMET; ÜYÜKLÜ, MEHMET; KOÇYİĞİT, ABDÜRRAHİM; KUMAŞ, MELTEM; EŞREFOĞLU, MUKADDES; ERGÜN, İLYAS SAMET; ÜYÜKLÜ, MEHMET; KOÇYİĞİT, ABDÜRRAHİM
Background: Ischemia-reperfusion injury causes various severe morphological and functional changes in diabetic patients. To date, numerous antidiabetic and antioxidant agents have been used for treatment of the disease-related changes. Objectives: We aimed to examine effective therapeutic doses or doses of berberine against renal ischemia/reperfusion injury (IRI) in a streptozotocin (STZ)-induced diabetic rat model by histopathological and biochemical analysis. Methods: Thirty male Sprague Dawley rats were treated with STZ injection for the development of diabetes, and divided into the following groups: STZ-induced diabetic group (STZ); IRI-induced diabetic group (STZ+IRI); 50mg/kg berberine (BRB) treated diabetic group after inducing IRI (STZ+IRI+BRB1); 100mg/kg BRB treated diabetic group after IRI (STZ+IRI+BRB2); 150mg/kg BRB treated diabetic group after IRI (STZ+IRI+BRB3). Bilateral renal ischemia model was applied for 45min, then reperfusion was allowed for 14 days in STZ-induced diabetic rats. Renal injury was detected histopathologically. Blood urea nitrogen (BUN), creatinine and lactate dehydrogenase (LDH) levels were measured in serum using the ELISA method. Total antioxidant status (TAS) and total oxidant status (TOS) of renal tissue was studied by spectrophotometric assay. Oxidative stress index (OSI) was calculated as TOS-to-TAS ratio. Tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), Na+/K+-ATPase (sodium pump), and Ca2+-ATPase (calcium ATPase) enzyme levels were measured in tissues using the ELISA method. Anti-apoptotic Bax and pro-apoptotic Bcl-2 protein levels were detected by Western blot analysis. All data were evaluated statistically. Results: The highest histopathological score was detected in the STZ+IRI group compared to the other group. BRB administration at the doses of 100mg/kg and 150mg/kg markedly improved renal injury. BUN and creatinine levels significantly increased in the STZ+IRI group compared to the STZ group (p<0.001). 100mg/kg and 150mg/kg BRB administration significantly decreased those levels (p<0.01). The highest TOS and the lowest TAS levels were detected in the STZ+IRI group (p<0.001). IRI markedly aggravated inflammation via increasing levels of TNF-α and CRP (<0.001), and caused apoptosis via inducing Bcl-2 protein, and suppressing Bax protein (p<0.001). BRB administration at the doses of 100mg/kg and 150mg/kg showed anti-oxidant, anti-inflammatory and anti-apoptotic effects (p<0.01). The LDH enzyme, was used as a necrosis marker, was higher in the STZ+IRI group than other groups. BRB administration at all of the doses, resulted in the decline of LDH enzyme level (p<0.001). Ca2+-ATPase and Na+/K+-ATPase enzyme activities decreased in the STZ+IRI group compared to the STZ group (p<0.001), while BRB administration at the doses of 100mg/kg and 150mg/kg significantly increased those of enzyme activities, respectively (p<0.05). Conclusion: Ischemia with diabetes caused severe histopathological and biochemical damage in renal tissue. The high doses of berberine markedly improved histopathological findings, regulated kidney function via decreasing BUN and creatinine levels, and rearranged intercellular ion concentration via increasing Na+/K+-ATPase and Ca2+- ATPase levels. Berberine showed anti-oxidant, anti-apoptotic, and anti-inflammatory effects. According to these data, we suggest that berberine at the doses of 100 and 150mg may be used as a potential therapeutic agent to prevent renal ischemic injury.