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
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, ABDÜRRAHİM
Polyphenols 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.
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.
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
Phyotherapeutic Properties of Urfa Pistachio Nuts (Pistacia vera L.)
(2018-07-01) Koyuncu, Ismail; KOÇYİĞİT, ABDÜRRAHİM; Dikme, Resat; SELEK, ŞAHBETTİN; KOÇYİĞİT, ABDÜRRAHİM; SELEK, ŞAHABETTİN
According to recent studies, the Urfa pistachio nut (Pistacia vera L.) is a rich source of phenolic components, with a high level of the three antioxidant substances of gallic acid, catechin, and epicatechin present together. The pistachio nut, which is in the top 50 foodstuffs with the highest antioxidant potential, is the only edible nut containing anthocyanin, which is the richest and has most variations of water and fat-soluble antioxidants. The pistachio nut also contains important bioactive polyphenol components, such as transreservatrol and isoflavones, which have anti-cancer potential. Some forms of the Pistachio species, including the Urfa pistachio nut, are used by the general population to improve the gastrointestinal, liver, urinary tract, and respiratory tract disorders and for various other purposes such as aphrodisiac, antiseptic, and antihypertensive effects. In some studies, it has been determined that the pistachio nut is beneficial in the continuation of mechanisms that provide maintenance of body health, such as anti-inflammatory activity, glycemic control, and endothelial functions, and it has also been shown to prevent the oxidation of low-density lipoprotein cholesterol and to have a protective role against chronic diseases such as cancer and cardiovascular disease. With a potassium content of 10.05 mg/gram, which is higher than other types of peanut, the sodium content of the pistachio nut may play a role in balancing the blood pressure by reducing the need for salt. This review is of importance in respect of the evaluation of the positive effect on several diseases of the kernel and particularly the shell extract of the pistachio nut.
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.
Open Access
Relationship between diabetic polyneuropathy, serum visfatin, and oxidative stress biomarkers
(2020-07-01T00:00:00Z) GÜLER, Eray Metin; BÜYÜKAYDIN, BANU; Karaaslan, Tahsin; OLGAÇ, ATİLLA; ZORLU, MEHMET; KISKAÇ, MUHARREM; KOÇYİĞİT, ABDÜRRAHİM; BÜYÜKAYDIN, BANU; GÜLER, ERAY METİN; OLGAÇ, ATİLLA; ZORLU, MEHMET; KISKAÇ, MUHARREM; KOÇYİĞİT, ABDÜRRAHİM
Background: Diabetic polyneuropathy is a very common complication of diabetes. Numerous studies are available in terms of pathogenesis. But examination methods with low reliability are still not standardized and generally time consuming. High-sensitive, easy-to-access methods are expected. Biochemical markers are one of the subjects of research. We aimed to discover a potential biomarker that can be used for this purpose in patients with diabetes who have not yet developed symptoms of neuropathy. Aim: To determine the place and availability of visfatin and thiol-disulfide homeostasis in this disorder. Methods: A total of 392 patients with type 2 diabetes mellitus were included in the study. The polyneuropathy clinical signs were evaluated with the Subjective Peripheral Neuropathy Screen Questionnaire and Michigan Neuropathy Screening Instrument questionnaire and examination. The biochemical parameters, oxidative stress markers, visfatin, and thiol-disulfide homeostasis were analyzed and correlated with each other and clinical signs. Results: Subjective Peripheral Neuropathy Screen Questionnaire and Michigan Neuropathy Screening Instrument questionnaire with examination scores were correlated with each other and diabetes duration (P < 0.005). Neuropathy related symptoms were present in 20.7% of the patients, but neuropathy related findings were observed in 43.9% of the patients. Serum glucose, glycated hemoglobin, and visfatin were positively correlated with each other. Also, these parameters were positively correlated with the total oxidative stress index. Total and native thiol was positively correlated with total antioxidant status and negatively with oxidant status. Inversely thiol-disulfide positively correlated with higher glucose and oxidant status and negatively with total antioxidant status (P < 0.005). There was no correlation between visfatin and thiol-disulphide (P = 0.092, r = 0.086). However, a significant negative correlation was observed between visfatin and total with native thiol (P < 0.005, r = -0.338), (P < 0.005, r = -0.448). Conclusion: Diagnosis of neuropathy is one of the issues studied in patients with diabetes. Visfatin and thiol-disulfide balance were analyzed for the first time in this study with inspiring results.