Objectives: Humans are unknowingly exposed to mycotoxins through the consumption of plant -derived foods and processed products contaminated with these toxic compounds. In addition to agricultural losses, Fusarium toxins pose a threat to human health. However, the effects of fusariotoxins on the viability and proliferation of stem cells have not been fully explored. We investigated the cytotoxic effects of deoxynivalenol (DON) and B-trichothecene mix (MIX) on mesenchymal stem cells (MSCs) and the L929 fibroblast cell line. Materials and Methods: MSCs were isolated from the dental pulp tissue. The doubling time and viability of dental pulp stem cells (DPSCs) and L929 cells were determined using the MTT assay. The following doses of B-trichothecenes (0.25-16 pg/mL; 24 hours and 48 hours) were used to evaluate cytotoxicity. In addition, changes in the confluency-dependent response of DPSCs to DON toxicity were determined. Moreover, we investigated the effect of DON on cell death via acridine orange/ethidium bromide (AO/EB) double staining. Results: A DON and MIX showed a dose- and time -dependent inhibitory effect on the proliferation of both cells. DPSCs exposed to DON for 48 hours (IC50 = 0.5 mu g/mL) were found to be 16 -fold more sensitive than L929 cells (IC50 = 8 mu g/mL). Compared with a culture with 80% confluency, DPSCs from a 50% confluent culture were more sensitive to varying doses of DON (0.25-4 pg/mL, 24-48 hours). Moreover, AO/EB staining showed that treatment of DPSCs with DON led to a significant increase in cell death (17% for 2.4 pg/mL; 50% for 4.8 pg/mL). Conclusion: This study reveals that undifferentiated MSCs are significantly more sensitive to DON than differentiated somatic cells (L929). Given that humans are frequently exposed to these mycotoxins, our findings imply that prolonged exposure to them may also have harmful effects on cellular differentiation and embryonic development.

Metformin, a widely used first-line medication in the treatment of type II diabetes, has been proposed to have a second indication in the treatment of cancers and aging. However, its accounting mechanisms in cellular physiology were not clearly understood. Therefore, its cytotoxicity and underlying physiological mechanisms should be explained. Schizosaccharomyces pombe was evaluated as a single-cell cytotoxicity model and was treated with metformin and grown on YEL media at 30 °C and 180 rpm. 0,1-20 mM metformin caused dose-dependent apoptosis and necrosis demonstrated by using Annexin V-FITC/PI and DAPI staining. Surprisingly, metformin reduced ROS levels with stable antioxidant enzyme levels, but the mitochondrial transmembrane potential was significantly increased indicating a differential regulation by the dual character of metformin. In addition, a possible role can be attributed to Cnx1 in apoptotic cell death; which showed a dramatic increase in transcription, however, three other potential apoptotic genes, Rad9, Pca1, and Aif1 were stable. To conclude, the dual effect of metformin was clarified, and related cellular physiological effects with accompanying mechanisms (particularly Cnx1-mediated) were shown using S. pombe.

Magnezyum, enerji metabolizması, nükleik asit ve protein sentezi, sinyal iletimi, hücre bölünmesi gibi birçok biyolojik süreç için hayati önem taşır. Magnezyum homeostasisinin bozulması, kardiyovasküler hastalıklar, hipertansiyon, tip 2 diyabet ve kanser başta olmak üzere çok sayıda hastalıkla ilişkilendirilmiştir. Dünya çapında 300 milyondan fazla insan tip 2 diyabet ile mücadele etmektedir ve bu sayı katlanarak artmaktadır. Klinik çalışmalar, tip 2 diyabetli hastalarda serum magnezyum seviyesinin düştüğünü ve magnezyum takviyesinin glukoz metabolizması üzerine olumlu etkileri olduğunu göstermiştir. Bu çalışmada, biyolojik süreçler ve genetik mekanizmalar bakımından memeli hücreleriyle benzerlik gösteren Schizosaccharomyces pombe mayasının magnezyum transportu kısıtlı mutant suşunda glukoz tüketimi ve glukoz taşıyıcılarının (ght1, ght2, ght5) anlatım seviyeleri araştırılmıştır. Magnezyum transportu kısıtlı olan mutant suşta, besi ortamına ilave edilen magnezyum artışına bağlı olarak glukoz tüketimi artmıştır. Glukoz taşıyıcılarından ght1, ght2 nin anlatım düzeyi, 30 mM Mg+2destekli ortamda artmış, suş için optimum üremenin görüldüğü daha yüksek magnezyum konsantrasyonunda (75 mM) azalmış, ght5’in anlatım düzeyinde ise anlamlı bir değişim bulunmamıştır. Bulgularımız, glukoz taşıyıcılarından ght1 ve ght2’ nin ght5’ ten farklı bir mekanizma ile düzenlendiğini işaret etmektedir.

Background/aim Tuberculosis is a public health problem that still remains significant. For prevention, diagnosis, and treatment of tuberculosis more effective novel biomarkers are needed. MicroRNAs can regulate innate and adaptive immune responses, alter host-pathogen interactions, and affect progression of diseases. The relationship between microRNA expression and active pulmonary tuberculosis (APT) has not yet been investigated in the Turkish population. We aimed to test the potential diagnostic value of some microRNAs whose levels were previously reported to be altered in APT patients. Materials and methods Using two different references (U6 and miR-93), we compared the expression levels of potentially important microRNAs in serum of APT patients with healthy individuals using quantitative polymerase chain reaction (qPCR). Results miR-144 expression level was down-regulated in APT patients when either U6 or miR-93 was used for normalization. When data was normalized with miR-93, a statistically significant decrease in miR-125b (0.8 fold) and miR-146a (0.7 fold) expression levels were observed, while no differences were detected for U6. The receiver operating characteristic suggested that miR-144 may be a candidate biomarker for discriminating APT patients and controls (p < 0.05) both for U6 and miR-93. Conclusion These findings suggest that miR-144 can have potential as a biomarker for APT. Using a single reference may be misleading in evaluation of microRNA expression. U6 and miR-93 can be used in combination as references for normalization of serum microRNA expression data.

In this study, we compared the effects of terpinolene against the anti-cancer agent cisplatin on proliferation, apoptotic activity and intracellular ROS (reactive oxygen species) production in cancerous (MCF-7) and non-cancerous (HEK-293) cell lines. Cisplatin presented a strong growth-inhibitory effect on both MCF-7 (IC25: 18.77 µM) and HEK-293 (IC25: 15.03 µM) cell lines. The growth-inhibitory effect of terpinolene was found to be weaker than cisplatin (IC25: 291.18 µM for MCF-7 and 345.35 µM for HEK 293 cells). The expression levels of BAX (by 1.86-fold), cleaved-PARP (by 2.23-fold) and pro-caspase-8 (by 1.74-fold) proteins increased in response to terpinolene treatment in MCF-7 cells. Curiously, the increase in the expression levels of these apoptotic markers was less pronounced in terpinolene-treated non-cancerous HEK 293 cells. Terpinolene, promoted a higher rate of apoptotic and necrotic cell death on MCF-7 cells (apoptotic cells: 25.28 %; necrotic cells: 17.70 %) when compared with HEK-293 cell line (apoptotic cells: 15.47 %; necrotic cells: 9.42 %). Interestingly, terpinolene caused a marked increase (2.05-fold) in intracellular ROS production in MCF-7 cells while HEK-293 cells appeared to be resistant to terpinolene or cisplatin treatments. In conclusion, although terpinolene showed a weaker growth-inhibitory effect on MCF-7 cancer cells, it exhibited a better selectivity than cisplatin in inducing cell death and intracellular oxidative stress in MCF7 breast cancer cells.

Objectives: Dehydroepiandrosterone (DHEA) is an endogenous hormone that acts as a ligand for several cellular receptors. An age-dependent decline in circulating levels of DHEA is linked to changes in various physiological functions. In gynecological clinical practice, DHEA is commonly prescribed to induce ovulation. Some clinical studies report a positive association between high serum concentrations of DHEA and an increased risk of developing ovarian cancer. However, the in vitro physiological effects of DHEA on ovarian cancerous cells have not been explored thus far. In this study, we aimed to investigate the physiological effects of DHEA treatment (0-200 mu M, 24-72 hours) on MDAH-2774 human ovarian cancer cell line and primary HuVeC human endothelial cells. Materials and Methods: The physiological effects of DHEA treatment (0-200 mu M, 24-72 hours) on MDAH-2774 human ovarian cancer cell line and primary HuVeC human endothelial cells were investigated with the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test, acridine orange/ethidium bromide staining, and scratch assay. Results: DHEA treatment promoted proliferation of the MDAH-2774 cancer cell line in a dose-dependent manner (r=0.6906, p<0.0001, for 24 hours) (r=0.6802, p<0.0001, for 48 hours) (r=0.7969, p<0.0001, for 72 hours). In contrast, DHEA inhibited proliferation of the primary HuVeC cells (r=0.9490, p<0.0001, for 24 hours) (r=0.9533, p<0.0001, for 48 hours) (r=0.9584, p<0.0001, for 72 hours). In agreement with these observations, DHEA treatment resulted in a dose-dependent increase in the number of necrotic cells in the primary HuVeC cells (r=0.97, p<0.0001). However, the number of necrotic or apoptotic cells did not change significantly when the MDAH-2774 cells was exposed to DHEA. Moreover, we found that DHEA treatment reduced the migration rate of HuVeC cells in a dose-dependent manner (r=0.9868, p<0.0001), whereas only a slight increase was observed in the MDAH-2774 ovarian cancer cell line (r=0.8938, p<0.05). Conclusion: Our findings suggest that DHEA promotes the proliferation of ovarian cancer cells in a dose-dependent manner in vitro. Moreover, DHEA induced necrosis and inhibited proliferation in endothelial cells. Although mechanistic evidence is required, our preliminary findings imply that exposure to high doses of DHEA may be associated with an increased risk of developing ovarian cancer.

Objective: In vitro evaluation of implant materials' effects on cell adhesion and viability can provide useful information for predicting implant biocompatibility. Therefore by using a simple and inexpensive method, it was aimed to investigate whether different implant surface-features might have distinct effects on the viability and adherence of the cells. Material and Methods: Different dental implant surfaces (anodized (AN), blasted wrinkled (BW), grit/acid etched (GA), and hydroxylapatite sprayed (HB)) were tested for their possible effects on adhesion and viability of the adherent human osteoblast cells by using an agar-based in vitro technique. Viability of the cells was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and trypan blue staining. Results: The rate of cell adhesion did not seem to be significantly affected by the differences in surface features of dental implants (AN:78.21±0.52; BW:78.22±0.48; GA:78.44±0.85; HB:77.26±0.96). The surface features of the dental implants had an impact on the viability of the attached cells on the implants. Viability of the attached cells was significantly higher on AN, BW, GA surfaces when compared to the HB surface (AN: 72.28±6.04, BW: 67.02±3.47, GA: 85.82±5.05, and HB: 27.98±10.47). Conclusions: In vitro findings suggests that AN, BW, GA surfaces may provide a better platform than HB surfaces to maintain the viability of bound cells.

We aimed to investigate the in vitro physiologic effects of xylene, chloroform, orange oil and eucalyptus oil solvents for dissolving gutta-percha on L929 and HOB cell lines; 2.5 and 10 μL mL-1 of these solvents were tested for 24, 48 and 72 h. Gutta-percha solvents inhibited the proliferation rate of fibroblasts in a dose- and time-dependent manner; however, no inhibition was detected in HOB (evaluated using MTT assay). None of the solvents induced apoptosis/necrosis in HOB cells at ≤2.5 μL mL-1 concentration in contrast to L929 (determined using acridine orange/ethidium bromide dual staining). Each solvent tested reduced the migration rate of both L929 and HOB cell lines in a dose-dependent manner (evaluated using a scratch assay). Gutta-percha solvents can damage fibroblast-rich tissues. Osteoblasts seemed to be more resistant to the tested solvents, and excessive extrusion of solvents from the root canal may also damage the periradicular tissues and reduce the ability to repair.

ObjectivesBetahistine is a histamine analog commonly prescribed for symptomatic treatment of vertiginous symptoms. In vitro studies have shown that betahistine was not toxic at the prescribed doses in a nasal epithelial cell line. However, the effect of betahistine on other cell types has not been studied. In this study, we aimed to investigate some of the physiological effects of betahistine on L929 fibroblast, A549 lung cancer, human umbilical vein endothelial (HUVEC), and Ishikawa endometrial cell lines.Materials and MethodsCellular proliferation was assed assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, apoptosis was evaluated by acridine orange-ethidium bromide staining, and cellular migration was assed assessed by scratch assay.ResultsBetahistine treatment (0.1-0.5 mg/mL, 24 hours) can inhibit cell proliferation and induce apoptosis in HUVEC, A549, Ishikawa, and L929 cell lines. Betahistine (≥0.1 mg/mL) significantly increased the number of apoptotic cells (HUVEC: 26.3%, A549: 17.3%, L929: 8.6%, and Ishikawa: 2.3%). Betahistine at doses over 0.1 mg/mL significantly suppressed the cell migration rate in all of the cell lines. In contrast, exposure to a low dose of betahistine (0.025 mg/mL) induced migration rates of HUVEC and Ishikawa cells by 81% and 48%, respectively.ConclusionBetahistine may alter the processes of cellular proliferation, apoptosis, and cellular migration in a cell line- and dose-dependent manner. In this sense, proliferative and metastatic properties of certain cancer cells can potentially be altered in response to betahistine treatment.

Objective: Inter-retrotransposon polymorphism Polymerase Chain Reaction (IRAP-PCR) technique allows for detecting insertional polymorphisms via amplification of the DNA fragment between two retrotransposons in plant genomes. However, this method has not been reported to be used for analyzing human samples to date. Recently, Human Endogenous Retrovirus (HERV) polymorphisms gained interest due to their potential effect on pathophysiology of certain diseases. Nevertheless, the association between HERV polymorphisms and the risk for developing nasal polyposis (NP) has not been studied. In this study, we aimed to investigate whether or not IRAP-PCR could be performed in nasal swab samples for comparing HERV polymorphisms in different nasal mucosal samples. Methods: Nasal swab samples from 16 patients were used for DNA isolation. These DNA samples were used as templates for IRAP PCR of HERV-K6, HERV-K11, HERV-L1 and HERV-L2 and PCR products were analyzed by agarose gel electrophoresis. Results: Nasal swab samples yielded enough DNA material for successfully performing IRAP-PCR. We obtained specific banding patterns the three out of four HERV sequences tested in this study. No polymorphisms was detected between samples from different patients. Similarly, polymorphic bands was not detected between the polyps or nasal mucosal swab samples obtained from the same patient. Conclusion: We have, for the first time, shown that IRAPPCR can be performed in nasal swabs. Our findings suggest that this technique can serve as an inexpensive and effective screening tool for investigating links between nasal mucosal diseases and HERV polymorphisms such as nasal polyposis.

Autophagy is an evolutionarily conserved catabolic mechanism, by which eukaryotic cells recycle or degrades internal constituents through membrane-trafficking pathway. Thus, autophagy provides the cells with a sustainable source of biomolecules and energy for the maintenance of homeostasis under stressful conditions such as tumor microenvironment. Recent findings revealed a close relationship between autophagy and malignant transformation. However, due to the complex dual role of autophagy in tumor survival or cell death, efforts to develop efficient treatment strategies targeting the autophagy/cancer relation have largely been unsuccessful. Here we review the two-faced role of autophagy in cancer as a tumor suppressor or as a pro-oncogenic mechanism. In this sense, we also review the shared regulatory pathways that play a role in autophagy and malignant transformation. Finally, anti-cancer therapeutic agents used as either inhibitors or inducers of autophagy have been discussed.

In this retrospective study, performed in the European region of Istanbul, it was aimed to investigate whether the birth month is a factor in inhalant allergen sensitivity in patients with symptoms similar to allergic rhinitis (AR). Skin prick test was applied to 3460 patients with symptoms similar to AR. The allergens used in the study were grouped according to their origin in four main categories: plants, fungi, house dust mites and animal epithelium (cat and dog). The results were retrospectively evaluated using SPSS analysis software. 2302 patients (66.5%) had at least one or more sensitization to the common inhalant allergens. Pollen sensitization was found to be the most common (53.8%) while sensitivity to the animal dander was the lowest (21.7%) among the individuals. Birth in June and July increased the risk for developing sensitization to the house dust mite (p< 0.012) whereas, birth in August was correlated with a lower risk of sensitization to Quercus Robur (p< 0.038). This study showed that individuals born in summer period can be at risk for developing HDM sensitizations. Thus, it is important to keep the house dust mites as low as possible by taking preventative measures in houses. Our findings may contribute to the planning of personalized preventive health care services for patients with AR-like symptoms.

Objective: Inter-retrotransposon polymorphism Polymerase Chain Reaction (IRAP-PCR) technique allows for detecting insertional polymorphisms via amplification of the DNA fragment between two retrotransposons in plant genomes. However, this method has not been reported to be used for analyzing human samples to date. Recently, Human Endogenous Retrovirus (HERV) polymorphisms gained interest due to their potential effect on pathophysiology of certain diseases. Nevertheless, the association between HERV polymorphisms and the risk for developing nasal polyposis (NP) has not been studied. In this study, we aimed to investigate whether or not IRAP-PCR could be performed in nasal swab samples for comparing HERV polymorphisms in different nasal mucosal samples. Methods: Nasal swab samples from 16 patients were used for DNA isolation. These DNA samples were used as templates for IRAP PCR of HERV-K6, HERV-K11, HERV-L1 and HERV-L2 and PCR products were analyzed by agarose gel electrophoresis. Results: Nasal swab samples yielded enough DNA material for successfully performing IRAP-PCR. We obtained specific banding patterns the three out of four HERV sequences tested in this study. No polymorphisms was detected between samples from different patients. Similarly, polymorphic bands was not detected between the polyps or nasal mucosal swab samples obtained from the same patient. Conclusion: We have, for the first time, shown that IRAPPCR can be performed in nasal swabs. Our findings suggest that this technique can serve as an inexpensive and effective screening tool for investigating links between nasal mucosal diseases and HERV polymorphisms such as nasal polyposis.

Introduction: In this cross-sectional study, we aimed to evaluate the distribution of allergic sensitivity to the common inhalant allergens in different age groups. We also aimed to determine the factors that may be associated with sensitization in adults from the European region of Istanbul. Materials and Method: Using SPSS statistical analysis software, we retrospectively evaluated Skin Prick Test (SPT) data from 2587 patients with symptoms similar to Allergic Rhinitis (AR). Results: Analysis of data revealed that that the frequency of sensitization to the common inhalant allergens significantly decreased by age. Animal dander was found to be the most common cause of allergic reactions among adult patients (p<0.05). When compared to the birth in other months, the frequency of sensitization to animal dander was significantly higher among individuals born in January (p<0.05). Gender-based analysis of the results revealed that the prevalence of sensitization to animal dander was significantly higher among females<45 y of age (p<0.05). The prevalence of sensitization to the inhalant allergens was found to be the lowest among elderly patients (42.9%; p<0.000). Conclusion: Personalized assessment of allergic conditions is important for planning a suitable treatment protocol for allergic diseases in the elderly. Our findings may contribute to design effective care plans and improve the environmental conditions for adult patients with symptoms similar to AR.

Malignant mucosal melanoma is an uncommon disease with a low rate of survival. Malignancies of nasal mucosa which usually presents with nasal obstruction, epistaxis and back drip are difficult to treat and often have poor prognosis. The present case had presented to our clinic with classic symptoms and diagnostic findings of nasal polyposis. Consistently, the patient had previously been diagnosed with and treated for nasal polyposis in another ENT clinic. Physical examination, rhinoscopic examination, computed tomography (CT) scan of the head did not reveal any findings which might imply malignant formations. The operation had been planned for nasal polypectomy and taking deep biopsy specimens. The incised mass showed characteristic features of malignant tissues and the pathology report of the biopsy samples revealed that the specimen showed the histological signs of malignancy. Based on physical examination, CT findings and pathology reports the case was diagnosed as nasal mucosal melanoma. Following an oncosurgical operation, postoperative radio-therapy and chemotherapy were given to the patient and PET/CT examination of the patient did not indicate distant metastases.

In tissue engineering, the importance of the natural or synthetic scaffold in a conversion and transplantation of three-dimensional structure of the produced cells is large (1). The formation of a functional vascular network resulting in new tissue is required for a successful tissue repair (2). Therefore using of decellularizated tissue as carrier support has advantages both in terms of comprising natural matrix and vascular supplying. In our study, decellularization methods of liver tissue for forming artificial liver and histologic examination of obtained matrix. The liver tissues were fixed in 10% neutral formalin and then embedded in paraffin blocks. Sections (2-4 μm thickness) were obtained using a sliding microtome from the prepared paraffin blocks. These sections were stained by Hematoxylin-Eosin (H-E). Later, the liver tissue sections were analyzed in the photomicroscope (Fig 1,2,3). Histological evaluation with H-E staining revealed less nuclei or cytoplasmic staining in decellularize groups (Fig 2,3) compared to normal rat liver (Fig 1). We showed that it was especially observed noticeable reduction hepatosit after the 5-hour desellülarization. In this study, it shown that the matrix with vascular network which is very important for tissue-engineering can be obtained in the liver, with an easy way, by desellülarization of tissue. In this way, produced hepatocytes can be easily clinging on a natural matrix and proliferating (3, 4).

Autophagy is biological mechanism allowing recycling of long-lived proteins, abnormal protein aggregates, and damaged organelles under cellular stress conditions. Following sequestration in double-or multimembrane autophagic vesicles, the cargo is delivered to lysosomes for degradation. ATG5 is a key component of an E3-like ATG12-ATG5-ATG16 protein complex that catalyzes conjugation of the MAP1LC3 protein to lipids, thus controlling autophagic vesicle formation and expansion. Accumulating data indicate that ATG5 is a convergence point for autophagy regulation. Here, we describe the scaffold protein RACK1 (receptor activated C-kinase 1, GNB2L1) as a novel ATG5 interactor and an autophagy protein. Using several independent techniques, we showed that RACK1 interacted with ATG5. Importantly, classical autophagy inducers (starvation or mammalian target of rapamycin blockage) stimulated RACK1-ATG5 interaction. Knockdown of RACK1 or prevention of its binding to ATG5 using mutagenesis blocked autophagy activation. Therefore, the scaffold protein RACK1 is a new ATG5-interacting protein and an important and novel component of the autophagy pathways.