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Background: Resistin is known as a potential mediator of obesity-associated insulin resistance. The high resistin level disrupts nitric oxide (NO)-mediated relaxation which is also important in erectile function. An antioxidant alkaloid, Boldine, is known as anti-diabetic and protects endothelial functions. Objectives: We aimed to investigate resistin expression in penile tissue in the presence of insulin resistance (IR) and the effect of Boldine treatment on erectile functions in the metabolic syndrome (MetS) rat model. Materials and methods: Wistar rats were randomly divided into three groups: Control, MetS, and boldine treated MetS group. MetS parameters were assessed by serum triglycerides (TG), uric acid (UA), glucose, insulin levels, HOMA index, and waist circumference (WC)/tibia length (TL) ratio. To evaluate erectile functions, intracavernous pressure (ICP)/mean arterial pressure (MAP) ratio was performed during cavernous nerve stimulation. Protein expressions of resistin, endothelial nitric oxide synthase (eNOS), p(S1177) eNOS, and insulin receptor-? were evaluated by Western blotting. Results: TG, glucose, insulin levels, weight, WC/TL ratio, HOMA index and resistin expression in penile tissue were significantly increased and ICP/MAP values, and p (S1177) eNOS expression in penile tissue were decreased in MetS group. Boldine treatment enhanced ICP/MAP values, insulin receptor-? and p(S1177) eNOS expressions compared with the MetS group. Discussion and Conclusion: MetS caused a deterioration in erectile function accompanied by an increase in resistin expression and a reduction in eNOS enzyme activation in the rat penile tissues. Boldine treatment resulted in an improvement in erectile function, independent of resistin expression. © 2020 American Society of Andrology and European Academy of Andrology, Türkiye Bilimsel ve Teknolojik Araştirma Kurumu, TÜBITAK: 114S792, This study was supported by the Scientific and Technological Research Council of Turkey (114S792).

Hepatocellular carcinoma (HCC) is strongly associated with metabolic dysregulations/deregulations and hyperglycemia is a common metabolic disturbance in metabolic diseases. Hyperglycemia is defined to promote epithelial to mesenchymal transition (EMT) of cancer cells in various cancers but its molecular contribution to HCC progression and aggressiveness is relatively unclear. In this study, we analyzed the molecular mechanisms behind the hyperglycemia-induced EMT in HCC cell lines. Here, we report that high glucose promotes EMT through activating c-Met receptor tyrosine kinase via promoting its ligand-independent homodimerization. c-Met activation is critical for high glucose induced acquisition of mesenchymal phenotype, survival under high glucose stress and reprogramming of cellular metabolism by modulating glucose metabolism gene expression to promote aggressiveness in HCC cells. The crucial role of c-Met in high glucose induced EMT and aggressiveness may be the potential link between metabolic syndrome-related hepatocarcinogenesis and/or HCC progression. Considering c-Met inhibition in hyperglycemic patients would be an important complementary strategy for therapy that favors sensitization of HCC cells to therapeutics.

Engineered silica nanoparticles (SiNP) are emerging materials for medical applications. Evaluating biological responses of specific cells treated with engineered silica nanoparticles is however essential. We synthesized and characterized the physicochemical properties of silica nanoparticles with two different sizes of 10 and 100 nm (10SiNP and 100SiNP) dispersed in cell culture medium. HuH-7, an epithelial-like human hepatoblastoma cell line and SK-HEP-1, a liver sinusoidal endothelial cell line (LSEC) are employed to evaluate their biological responses for the SiNP treatment. Primary human lymphocytes are used to assess genotoxicity recommended by OECD guidelines while erythrocytes are used to assess hemolytic activity. The engineered silica nanoparticles are not able to produce radical species, to alter the mitochondrial membrane potential, and induce any adverse effects on cell proliferation. The colony formation ability of HuH-7 hepatoblastoma cells was not affected following the SiNP treatment. Furthermore, SiNPs do not induce hemolysis of red blood cells and are not genotoxic. These findings suggest that SiNPs regardless of the size, amount, and incubation time are biologically safe vehicles to deliver drugs or genes to the liver. © 2020 Elsevier B.V., İzmir Yüksek Teknoloji Enstitüsü, İYTE: 2012IYTEBAP06, This work was supported by the Izmir Institute of Technology [grant number 2012IYTEBAP06 ].

Introduction: Type 2 diabetes mellitus (DM) is a major risk factor for cardiovasculardiseases and is responsible for the increase in cardiovascular mortality.Chronic hyperglycemia is related to accelerated atherosclerosis. In this study,we tried to demonstrate the relation between glycosylated hemoglobin (HbA1c)level, which is a marker of long-standing hyperglycemia, and aortic stiffness,which is a marker of cardiovascular disease.Patientsand Methods: In total, 100 patients withtype 2 DM were included in this study. Patients were divided into three groupsaccording to the HbA1c level (group 1 HbA1c ≤ 6, group 2 HbA1c between 6 and 7,and group 3 HbA1c ≥ 7).Results: Significant correlation was found between aortic distensibility andHbA1c level (r= 0.283, p= 0.004). Moreover, aortic distensibility was alsocorrelated with the duration of DM (r= −0.172, p= 0.05) and age (r= -0.27, p=0.006). Significant correlation was determined between aortic strain andfasting blood glucose level, HbA1c level, and the duration of DM (r= −0.265, p=0.008; r= 0.279, p= 0.005; and r= −0.14, p= 0.03, respectively).Conclusion:In this study, we showed that aortic stiffness was increased in patients withtype 2 DM who have high blood fasting glucose and HbA1c levels. Our study alsoshowed that the duration of DM was related to aortic stiffness.Echocardiographic non-invasive evaluation of aortic stiffness may be helpful inthe estimation of cardiovascular risk in patients with DM., Giriş: Tip 2 diabetes mellitus (DM) kardiyovasküler hastalıklar için major riskfaktörüdür ve DM’li hastalar artmış kardiyovasküler mortalite ve morbiditeyesahiplerdir. Kronik hiperglisemi ile ilişkili olan birçok mekanizma buhızlanmış aterosklerozdan sorumlu tutulmaktadır. Bu çalışmada amaç DM’lihastalarda uzun dönem glisemik kontrolün belirteci olan HbA1c seviyesi ilekardiyovasküler hastalıkların belirteci olan aortik sertlik arasındaki ilişkiyisaptamaktır.Hastalarve Yöntem: Çalışmamıza kliniğimize başvuran Tip 2 DM’li 100hasta alındı. Hastalar HbA1c değerlerine göre üç gruba ayrıldı.Bulgular: Gruplar arasında açlık kan şekerleri, DM süresi ve oral antidiyabetik yada insülin kullanımında istatistiksel olarak anlamlı şekilde farklı bulundu.Aortik esneyebilirlik ve HbA1c düzeyi arasında önemli ilişki bulundu (r= 0.283;p= 0.004). Bunun yanı sıra, DM süresi (r= -0.172; p= 0.05) açlık kan şekeri(r=0.292; p= 0.003) ve hasta yaşı ile (r= -0.27; p= 0.006) aortikesneyebilirlik arasında da istatistiksel anlama ulaşan korelasyon tespitedildi. Bunun yanında aortik gerilim ile açlık kan şekeri, HbA1c, DM süresiarasında (sırasıyla; r= -0.265; p= 0.008, r= 0.279; p= 0.005 ve r= -0.14; p=0.03) anlamlı korelasyon bulundu.Sonuç:Bu çalışmada, yüksek açlık kan şekeri ve HbA1c düzeyine sahip tip 2 diyabethastalarında aortik sertliğin arttığını gösterdik. Aynı zamanda çalışmamızdiyabetin süresi ile aortik sertliğin ilişkili olduğunu göstermiştir. Ekokardiyografiylenoninvaziv yöntem olarak ölçülen aortik elastisite parametreleri hastalığın erkendöneminde kardiyovasküler riski tahmin etmede ve önlemede faydalı olabilir.

Hyperlipidemia is an important risk factor for atherosclerosis and is frequently seen in patients with erectile dysfunction (ED). This study was designed to evaluate whether the acute effect of native low-density lipoprotein (nLDL) on intracavernosal pressure (ICP) is reversible and related to plasma asymmetrical dimethylarginine (ADMA), endogenous inhibition of endothelial nitric oxide synthase (eNOS) levels and eNOS expression in cavernous tissues. Hyperlipidemia was induced by a single dose of intravenous 4 mg kg(-1) nLDL. Experiments were performed 72 h (72H), 2 weeks (2W) and 8 weeks (8W) after nLDL injection. Endothelium-dependent relaxations, the ratio of ICP to mean arterial pressure (MAP; ICP/MAP), plasma ADMA levels and eNOS mRNA and protein levels were evaluated. The ICP/MAP ratio decreased in both the 2W and 8W groups. Endothelium-dependent relaxation responses to acetylcholine in the rat thoracic aorta were damaged in the 8W group. Plasma ADMA levels increased in the 8W group. mRNA expression of eNOS decreased in a time-dependent manner, whereas the protein expression increased. These results suggest that acute nLDL injection-induced impairments in erectile functions during an 8-week period are irreversible and might be related to an increase in ADMA levels and changes in the regulation of the eNOS/NO pathway.

e15057 Background: In women, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death worldwide. Tamoxifen is the most commonly used drug for the endocrine treatment of breast cancer. It reduces the risk of recurrence and death from breast cancer when given to estrogen-receptor-positive breast cancer patients. It has recently been shown that imidazoles, an antifungal drug, possess anticancer potentials, and it can be a novel therapeutic in cancer treatment. However, the effects of combined treatment with imidazole and tamoxifen are unknown in estrogen receptor-positive breast cancer cell lines. Our study aimed to investigate the effects of imidazole and tamoxifen combination in estrogen receptor-positive breast cancer cell lines. Methods: MCF7 cell line, an estrogen receptor-positive breast cancer cell line, was used in this study. Following 24 hours 50 mM imidazole (molecular grade) treatment, 15µM tamoxifen was treated to MCF-7 cells by 72 hours. As control groups, following for 24-hour imidazole alone treated, only medium treated cells for 72 hours were used. MTT assay was performed for the determination of cell viability. Apoptosis was shown using acridine orange/ethidium bromide staining. The cellular morphological alterations were observed on bright-field microscopy using Giemsa staining. Cell migration status was determined using by in vitro scratch assay. Results: MTT assay results showed that tamoxifen alone treatment for 72 hours decreased cell viability by 18 percent (p < 0.001). On the other hand, cell viability is not affected by imidazole alone treatment for 24 hours compared with the control group (p > 0.05). However, it was calculated that 24 hours of imidazole followed by tamoxifen for 72 hours decreased cell viability up to 42 percent (p < 0.001). Tamoxifen alone group, compared with combined treatment with tamoxifen and imidazole, observed an increase of apoptotic cell numbers in combined treatment with tamoxifen and imidazole group, statistically significantly (p < 0.01). It was observed that cellular morphology was affected by combined treatment with tamoxifen and imidazole. Giemsa staining results showed that MCF 7 cells changed their cellular morphology, lost cell-cell contact, differentiated from parental morphology and cellular morphology, and appeared unhealthy. Parallel to these findings, a decrease in cell migration was observed in the combined-treated group compared to the tamoxifen alone group (p < 0.01). Conclusions: Our results showed that sequential usage of imidazole followed by tamoxifen has an enhanced anticancer effect of tamoxifen in estrogen receptor-positive breast cancer cell lines. These results allow us to establish a new hormonal treatment for patients with breast cancer.

Introduction Lab-on-a-chip (LOC) systems can present cells multiple cues that cells are subjected to, including gradients of cytokines and secreted proteins from neighbouring cells, biochemical and mechanical interactions with the extracellular matrix, and direct cell-to-cell contacts in a controllable and reproducible fashion. Simulating microenvironment with LOC devices is crucial to understand metastasis preference of cancer cells especially for planning personalised therapies in hepatocellular carcinoma (HCC). Material and methods Peristaltic-pump was used to circulate HCC cells, HuH-7 and SNU-449. Survival under shear stress was analysed by fluorometric and microscopic analysis. Adhesion and proliferation were measured by live cell analysis system. HUVEC cells were used to simulate extravasation of circulating cells. BEAS2B, HS-27A and THLE-2 cells were used as homing targets to simulate bone, lung and liver, respectively. Image analysis was performed with fluorescent and confocal microscopy. Results and discussions Firstly, we determined the effect of shear stress in a time-dependent manner on adhesion and proliferation of HCC cells. Circulation under shear stress up to 30’ caused an increase in both adhesion and proliferation significantly, whereas longer exposure time has a negative effect on adhesion, proliferation and, survival. HuH-7 cells with epithelial phenotype found to gain increased survival capacity under shear stress than its mesenchymal counterpart SNU-449. Then, we investigated the homing preference of HCC cells by using a novel micro-circulation LOC device. Shear stress, microenvironmental conditions (medium, matrigel, coating, etc.), cell labels and numbers (homing, HCC) were optimised for LOC. Representation of endothelial barrier was succeeded by monolayer coating of ’flow-channel’ by HUVEC cells. HCC cells were circulated for 4 hours then LOCs were incubated for 3 days. The extravasation and homing preference of HCC cells were determined by confocal imaging. Consistent with the high frequency of intrahepatic metastasis in HCC, SNU-449 cells mostly preferred to home into the channel with normal liver cells. Conclusion Our study suggests designed LOC system has a potential to predict homing capacity and organ preference of circulating tumour cells in HCC. In addition to precision medicine applications such as drug screening, this device could be used as a three-dimensional tool for understanding tumor-microenvironment interactions with mechanistic explanations in metastasis.

The purpose of this study was to show the clinical characteristics of microtia and congenital aural atresia cases in Turkey and to make the classification. For this purpose, records of 28 patients with microtia who were admitted to the ENT Clinic of Eskisehir Military Hospital, Turkey, between 1995 and 2011 and 3 patients admitted to the ENT outpatient clinic of Kocaeli Derince Education and Research Hospital, Turkey, were analyzed retrospectively. Of the total 31 patients with microtia (35 microtic ears), involvement of the right ear of 20 patients (64.5%), the left ear of 7 patients (22.5%), and bilateral involvement in 4 patients (12.9%) were observed. There was a unilateral involvement in 27 patients (87.1%). According to the Marx grading, 2 patients (5.7%) had grade 1 malformation, 3 (8.6%) had grade 2 malformation, 29 (82.9%) had grade 3 malformation, and 1 (2.9%) had grade 4 malformation (anotia). Although the characteristics of microtia vary in different population, the results in Turkey are consistent with those in the literature.

BACKGROUND/AIMS Gastric cancer (GC) is the second most common malignancy worldwide, with a high mortality rate. The incidence of GC has declined in the western countries during the last decades. The glutathione S-transferases comprise a group of enzymes that are critical in the detoxification of carcinogens. In this study we aimed at the relationship GSTP-1 methylation in patients with intestinal metaplasia with and without Helicobacter pylori infection, gastric cancer and controls. METHODOLOGY The methylation status of GSTP1 gene was analyzed by methylation specific PCR after bisulfate modification in H. pylori (+) (n=25) and (-) (n=25) intestinal metaplasia (IM) patients, GC (n=25) and control subjects (n=15) between September 2009 to November 2011. RESULTS During the study period 90 patients who underwent endoscopic examination were included in the study. When we considered the GSTP1 gene methylation profile in all of the groups; 26 (28%)patients had methylated GSTP1 gene, 31 (34%) patients had unmethylated GSTP1 gene and 33 (36%) patients had heterogeneously methylated GSTPI gene. CONCLUSIONS GSTP1 gene methylation profile is not appropriate for early diagnosis of cases with gastric cancer.

Gastroesophageal reflux disease is a risk factor for esophageal adenocarcinoma yet studies that have investigated the relationship between erosive esophagitis and esophageal adenocarcinoma have usually focused on symptom-related evidence or polymorphisms. There are no epigenetic gene expression studies on this topic. In this study, we aimed to evaluate the relationship between erosive esophagitis and esophageal adenocarcinoma to identify whether there is a genetic predisposition for esophageal adenocarcinoma. The Human Epigenetic Chromatin Modification Enzyme RT(2) Profiler(™) PCR array (PAHS-085A) was used to detect the expression of 84 key genes encoding enzymes. This was carried out prospectively for samples from 60 patients (20 patients as a control group, 20 patients with erosive esophagitis and 20 patients with esophageal adenocarcinoma). AURKA, AURKB, NEK6 were expressed at significantly higher levels in esophageal adenocarcinoma compared to the control group. MBD2 was expressed at significantly lower levels in the esophageal adenocarcinoma group compared to the control group. AURKA, AURKC, HDAC9 and NEK6 were expressed at significantly higher levels in erosive esophagitis compared to the control group. There was no difference in upregulated gene expression between the erosive esophagitis and esophageal adenocarcinoma. MBD2 was significantly downregulated in esophageal adenocarcinoma compared to erosive esophagitis. NEK6 and AURKA were significantly upregulated in esophageal adenocarcinoma and erosive esophagitis compared to the control group. This is a novel study on the genetic predisposition for erosive esophagitis and esophageal adenocarcinoma. AURKA and NEK6 are two promising genetic markers for erosive esophagitis and esophageal adenocarcinoma.

Background: Mitral stenosis (MS) is still the most common complication of acute rheumatic fever in Turkey. Rheumatic carditis affects not only cardiac valves but also myocardium. In this study, we aimed to evaluate the subclinical left ventricular (LV) systolic dysfunction and contraction of short and long axial circumferential and longitudinal fibers by pulsed wave tissue Doppler in rheumatic MS patients who have preserved LV systolic function in 2D echo-cardiography. Methods: Fifteen severe, 20 moderate rheumatic MS patients hospitalized for mitral balloon valvuloplasty, and 15 patients who had normal echocardiographic findings were included in the study. After routine conventional transthoracic echocardiographic examination, LV myocardial systolic velocities were evaluated with pulsed wave tissue Doppler in the short and long axis with simultaneous electrocardiographic monitoring. Results: Long axis first systolic velocity (SW1) of mild-moderate and severe MS was much lower than normal group (10.7 ± 2.3 in normal group vs. 7.9 ± 1.3 in mild-moderate MS group vs. 6.2 ± 1.4 in severe MS group, p < 0.001). Long axis Q-SW1 duration was longer in mild-moderate MS group (145 ± 32 in normal group vs. 199 ± 43 in mild-moderate MS group, p = 0.001). Short axis Q-SW2 duration was longer in normal group compared to mild--moderate and severe MS groups (298 ± 41 in normal group vs. 245 ± 37 in mild-moderate MS group vs. 234 ± 26 in severe MS group, p < 0.001). Significant correlation between mitral valve area and SW1, Q-SW1 was determined (p = 0.01). Conclusions: Even if LV functions are normal with conventional 2D echocardiography, subclinical systolic dysfunction exists in MS. Also, there is a dyssynchrony between contraction of longitudinal and circumferential myofibrils. © 2014 Via Medica.