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Background Biallelic QRSL1 mutations cause mitochondrial ‘combined oxidative phosphorylation deficiency-40’ (COXPD40). COXPD40 has been reported to be invariably lethal in infancy. Adrenal insufficiency was weakly reported and investigated among seven previously reported patients with COXPD40. Objective We report the clinical, biochemical, molecular, and functional characteristics of a patient with adrenal insufficiency due to COXPD40. Methods The medical history and adrenal function tests were examined. Genetic analysis was performed using whole-exome sequencing. Mitochondrial function was tested using mitochondrial membrane potential (MMP) and superoxide dismutase (SOD) enzyme assays. Results An 8-year-old boy was investigated for adrenal insufficiency. He also had mild developmental delay, sensorineural hearing loss, hypertrophic cardiomyopathy, nephrocalcinosis, elevated parathyroid hormone and creatine kinase, and lactic acidosis. Biallelic novel QRSL1 variants (c.300T>A;Y100* and c.610G>A;G204R) were identified. Oxidative damage in mitochondria was shown by reduced MMP and SOD assays in the patient compared to controls (P Conclusion Biallelic QRSL1 mutations can cause non-CAH PAI. Adrenal functions should be monitored in mitochondrial disorders to improve clinical outcomes.

Background and Objective: Curcumin is an effective anti-cancer agent used in thyroid cancer treatments. However, its use in clinical applications is limited due to low solubility and bioavailability. In this study, a novel combination strategy was applied by combining curcumin with Suberoylanilide Hydroxamic Acid (SAHA) to increase both bioavailability of curcumin and the efficiency of SAHA, which have limited efficiency when used alone. Methods: MTT assay was used to determine the cell viability of B-CPAP cells upon treatment with SAHA, curcumin and their combinations. Synergistic interactions between two agents were analyzed by Calcusyn software. Apoptosis and cell cycle assays were measured by flow cytometry. Expressions of apoptotic and cell cyclerelated proteins (PARP, P21/CDKN1A/WAF1, P27/KIP1) were examined by western blot analysis. Broth microdilution assay was performed to determine Minimum Inhibitory Concentration (MIC) values against S. aureus. Results: Based on MTT assay, IC50 values for SAHA and curcumin were determined as 0.91μM and 20.97μM, respectively. The combination index CI value was determined as 0.891 in B-CPAP cells, which demonstrate synergistic activity. The apoptotic effect was achieved by combination treatment (51.85%) on B-CPAP cells using half of the dose required for SAHA and curcumin alone. Combination treatment showed a significant increase in the percentage of B-CPAP cells in the S-phase due to cell arrest. Cleaved-PARP, P21/CDKN1A/ WAF1 and P27/KIP1 protein expressions were upregulated. Curcumin was found to have better anti-microbial activity than SAHA as having a lower MIC value, and checkerboard synergy analysis revealed that the two compounds co-operate synergistically for the in vitro killing of S. aureus. Conclusion: In the present study, synergistic combinations of SAHA and curcumin were shown to have both anti-cancer and antibacterial activities that would provide a novel thyroid cancer treatment strategy.

Background: Different cellular responses influence the progress of cancer. In this study, the effects of hydrogen peroxide and quercetin induced changes on cell viability, apoptosis, and oxidative stress in human hepatocellular carcinoma (HepG2) cells were investigated. Methods: The effects of hydrogen peroxide and quercetin on cell viability, cell cycle phases, and oxidative stress related cellular changes were investigated. Cell viability was assessed by WST-1 assay. Apoptosis rate, cell cycle phase changes, and oxidative stress were measured by flow cytometry. Protein expressions of p21, p27, p53, NF-Kβ-p50, and proteasome activity were determined by Western blot and fluorometry, respectively. Results: Hydrogen peroxide and quercetin treatment resulted in decreased cell viability and increased apoptosis in HepG2 cells. Proteasome activity was increased by hydrogen peroxide but decreased by quercetin treatment. Conclusion: Both agents resulted in decreased p53 protein expression and increased cell death by different mechanisms regarding proteostasis and cell cycle phases.

Objectives Transient Ischemic Attack (TIA) is due to a temporary lack of adequate blood and oxygen to the brain. TIAs typically last less than 24 hours. 10-15% of ischemic stroke patients have a history of TIA. 18% of them experience an ischemic stroke within 90 days, and the ABCD2 scoring system is used to estimate the risk. Our study aims to investigate the risk factors, the etiology, the lesion occurrence on MRI and the near-term risk of stroke of patients on whom TIA was diagnosed. Methods In this study, 124 patients were included between January 2012 and January 2018. Sixty-eight of the 124 patients were male. The history of patients was questioned; systemic and neurological examinations were made. The stroke risk factors and TIA duration were noted and ABCD2 scores were calculated. All the patients' blood samples, including glucose and lipid profile, were studied. They received CT, DWI MRI, electrocardiography, transthoracic echocardiography, ultrasound and/or MR angiography of the cervical arteries. Results One hundred twenty-four patients were included in this study, and 56 patients were female. The mean age was 63.04±16.77. Hypertension was the most common risk factor (50.8%). Twenty-seven patients were on antithrombotic; six patients were on anticoagulant therapy, while 91 patients were not receiving any antiaggregan therapy. ABCD2 scores were significantly higher on the antithrombotic therapy group (p=0.019). In 52 patients ABCD2 score was below 4, and in 72 patients, the score was greater than 4. In 67.7% of patients, no etiology was found. An ischemic lesion was detected in 16.9% of the patients. 58 % of the patients were discharged on anticoagulant therapy. Five patients developed ischemic stroke. Conclusion The risk factors of ischemic stroke and TIAs are similar factors. The etiology of TIAs cannot be found out in most of the patients. Thus, the patients are discharged with oral anticoagulant treatment.

Aim:Awareness of the community and healthcare professionals is crucial in the management of stroke. In this study, we aimed to investigate stroke awareness of patient relatives and healthcare professionals (excluding medical doctors) and how much they can show proper behavior towards patients during acute stroke.Methods:Healthcare professionals working in our hospital, relatives of patients who were hospitalized or were attending our outpatient clinics for follow-up due to stroke between August 2018 and November 2018 and community-dwelling healthy subjects (control group) who have not met any stroke patients were included in the study. Sociodemographic characteristics of the participants were recorded and a questionnaire investigating stroke findings, emergency approaches and risk factors prepared by the researchers was administered to the participants.Results:A total of 669 people, 236 healthcare professionals, 268 patient relatives and 165- controls, participated in this study. It was revealed that the patient relatives and the controls obtained information regarding stroke mostly on the internet (p=0.001). The relatives of patients received information from healthcare professionals at the third frequency. Healthcare professionals were found to be aware of the fact that stroke was treatable (p≤0.005) whereas the patient relatives and controls did not have adequate information 77% of the health professionals, 46% of the patient relatives and 34% of the controls stated that calling medical emergency service was the first choice approach. Seventy-three point seven percent of the health professionals, 38% of the relatives and 24% of the controls chose the correct answer which is “stroke patient should be transferred to emergency department within the first 4.5 hours following a stroke attack”.Conclusion:In terms of stroke awareness, three groups had a high level of awareness about stroke. It was observed that the three groups did not have sufficient information of early treatment of stroke.

Flavonoids are phenolic substances with chemo-preventive and chemotherapeutic properties. They are widely found in fruits and vegetables. The polyphenols quercetin and curcumin have antioxidant, anti-inflammatory, anti-carcinogenic, and pro-apoptotic properties. They were successfully used against different human cancers, especially chronic myeloid leukemia cancer cells. We have previously investigated anti-proliferative and apoptotic effects of quercetin and curcumin combination in K562 cells. Our data showed that they had beneficial synergistic effects. Based on these findings, we aimed to clarify signaling pathways involved in synergistic combination treatment with quercetin and curcumin in these cells. Proteins were investigated by Western blotting and by confocal microscopy. Changes in several genes in 10 different pathways related to cell proliferation, apoptosis, cell cycle, inflammation, hypoxia and oxidative stress were observed. Combination of quercetin and curcumin was effective on genes that were particularly related to p53, NF-kappa B and TGF-alpha pathways. Down-regulatory (CDKN1B, AKT1, IFN-gamma) and up-regulatory (BTG2, CDKN1A, FAS) effects on genes and related protein expressions may provide a multi-targeted therapy potential for chronic myeloid leukemia cancer cells without affecting healthy cells.

Objective: Tideglusib is a GSK-3 inhibitor activating Wnt/β-catenin signaling pathway which has significant importance in regenerative response.The aim of this study was to evaluate the cytotoxicity and protein expression impacts of Tideglusib on human periodontal cell lines.Methods: Cytotoxicity effect of different concentrations (50nM, 100nM, 200nM) of Tideglusib application on human gingival fibroblast (hGF),periodontal ligament fibroblast (hPDLF), and osteoblast (hOB) cell lines was determined. Type-I and III collagen expressions were evaluatedafter 24-hour application of 50nM Tideglusib.Results: The cytotoxicity of 200nM Tideglusib was higher in hGF and hOB (p0.05). The hGF and hOB treated with 50nM Tideglusib expressed an increased level of Type-I collagen (p0.05). Type-III collagen expressions were similar between thetest and control groups for each cell line (p>0.05).Conclusion: Tideglusib is not cytotoxic at 50nM and 100nM concentrations and may have positive effect on bone regeneration rather thanperiodontal regeneration since it stimulated Type-I collagen production in hGF and hOB cells, but not in hPDLF.

The aim of this study is to determine the cytotoxicity of three different nano composite resins (CRs) on human gingival fibroblast (hGF) and periodontal ligament fibroblast (hPDLF) cell lines. These CRs selected were nanohybrid organic monomer-based Admira Fusion (AF), nanohybrid Bis-(acryloyloxymethyl) tricyclo 5.2.1.0.sup.2,6 decane-based Charisma Topaz (CT), and supra nano filled resin-based Estelite Quick Sigma (EQS). MTT assay was performed to assess the cytotoxicity of CRs at 24 h and one week. AF and EQS applied on hGF cells at 24 h and one week demonstrated similar cytotoxic outcomes. Cytotoxicity of CT on hGF cells at one week was higher than 24 h (p = 0.04). Cytotoxicity of CT on hGF cells was higher at 24 h (p = 0.002) and one week (p = 0.009) compared to control. All composites showed higher cytotoxicity on hPDLF cells at one week than the 24 h (AF, p = 0.02, CT, p = 0.02, EQS, p = 0.04). AF and EQS demonstrated lower cytotoxicity on hPDLF cells than the control group at 24 h (AF, p = 0.01, EQS, p = 0.001). CT was found more cytotoxic on hPDLF cells than the control (p = 0.01) and EQS group (p = 0.008) at one week. The cytotoxicity of CRs on hGF and hPDLF cells vary, according to the type of composites, cell types, and exposure time.

Summary Background Walnuts contain many components including specific fatty acids, which could be active against cancer. Even though the anticarcinogenic effect of some of the individual fatty acids in walnut oil has been described, the effect of walnut oil itself on esophageal cancer cells hasn't yet been investigated. Objective We aimed to investigate whether walnut oil affects tumor growth and metastatic potential in esophageal cancer cells. Methods The human esophageal adenocarcinoma cell line, OE19, was treated with different doses of walnut oil and cell viability, apoptosis/necrosis and cell cycle analyses were performed using WST-1 assay and flow cytometry respectively. Adhesion, colony formation and wound healing assays were performed to assess the antimetastatic effects of walnut oil. NFkB expression was evaluated with western blot analysis. Results Walnut oil decreased the cell viability of esophageal cancer cells in a dose-dependent manner. 20 mg/mL walnut oil reduced cell viability by ∼50% when compared with control. The analysis revealed that necrosis and accumulation of cells in G0/G1 phase was induced in the cells treated with high doses of walnut oil. It also down-regulated the protein levels of NFkB. Walnut oil suppressed the adhesion, migration and colony formation of the cells. Conclusions High-dose short-term administration of walnut oil reduces the cell viability and metastatic ability of esophageal cancer cells, while exhibiting anticarcinogenic effect by inducing necrosis and cell cycle arrest at the G0/G1 phase, probably through suppression of the NFkB pathway. These data indicate that walnut oil, and by extension walnut consumption, may have beneficial effects in esophageal cancer in humans. This should be tested by clinical trials in the future.

Amaç: Kanser hücreleri aerobik koşullar altında Warburg etkisiolarak bilinen artmış glikolitik fenotipini sergilerler. Ayrıca,son zamanlarda yapılan çalışmalar, kanser hücrelerinin glikozabağımlı olduğunu ve keton cisimlerini birincil bir enerji kaynağıolarak kullanamadığını göstermiştir. Bu çalışmada, insan memekanseri hücrelerinin birincil enerji kaynağı olarak keton cisimlerinikullanamayacağını varsaydık ve keton cisimlerinin hücre canlılığıüzerine etkisini araştırdık.Gereç ve Yöntem: Bu çalışmada insan meme kanseri hücre hattı(MCF-7) ve insan foreskin fibroblast hücre hattı (HFF) kullanıldı.Her iki hücre hattında glukoz içeren ve içermeyen ortamlardaketon cisimleri olan asetoasetat ve beta-hidroksibütiratın hücrecanlılığına etkisini inceledik.Bulgular: Keton cisimlerini içeren ortamda MCF-7hücrelerinde hücre canlılığı kontrol ortamı ile karşılaştırıldığındaazalırken, kontrol olarak kullanılan HFF hücrelerinde herhangi birdeğişiklik görülmedi.Sonuç: Elde edilen veriler ışığında, keton cisimlerininkullanılması ile gerçekleştirilecek beslenmenin meme kanseritedavisinde yeni bir strateji olabileceğini düşünmekteyiz., Objective: Cancer cells exhibit an elevated glycolytic phenotypeunder aerobic conditions, which is known as the Warburg effect.Recent studies have also shown that cancer cells are glucosedependentand cannot use ketone bodies as a primary source ofenergy. In this study, we have investigated the effects of ketonebodies on viability of breast cancer cells considering that breastcancer cells would not use ketone bodies as a primary energysource.Materials and Methods: In this study we have used MCF-7cells, which are breast cancer cells that cannot use ketone bodiesas a primary energy source and human foreskin fibroblast cells(HFF) as controls. We measured cell viability in both cells culturedin the presence or absence of glucose as well as the ketone bodiesacetoacetate and beta-hydroxybutyrate.Results: Cell viability was significantly decreased in responseto ketone bodies compared with control media in MCF-7 cellswhereas in control cells (HFF) cell viability was not changed.Conclusion: In light of the data obtained, we suggest thatdietary manipulation with the use of ketone bodies may be a newtherapeutic strategy for breast cancer.

Objective: In this study we aimed to evaluate the effects ofcasein and whey protein supplementation on examinationstress. We have investigated different parameters of oxidativestress and immune function.Materials and Methods: The participants were dividedinto three groups: control, casein and whey. Casein and wheygroups were supplemented with either casein or whey proteinfor 15 days. Blood samples were obtained at the beginning ofthe study (Day 0), on the examination day (Day 16) and fivedays after the examination (Day 21). Antioxidant capacity,glutathione, cortisol and cytokine levels (TNF-a, IL-6, IL-12)were measured.Results: An increase in antioxidant capacity and glutathionelevels of the participants using whey protein was observed.Whey protein supplementation did not affect cortisol levels, butparticipants taking whey protein showed an increase in serumTNF-a and IL-6 levels.Conclusion: It is suggested that the use of whey proteinstrengthens the response to oxidative stress by increasingantioxidant capacity and glutathione levels, while supportingthe immune system via cytokine release.

Polifenoller bitkilerin koklerinde, sebzelerde, meyvelerde ve cay, kahve, kakao, sarap gibi bitkisel urunlerde yuksek miktarlarda bulunurlar. Polifenollerin antioksidan, anti-kanser, anti-inflamatuvar, anti-koagulan ve anti-mikrobiyal etkileri oldugunu belirten cok sayida arastirma bulunmaktadir. Son yillarda arastiricilar bu bilesiklerin anti-kanser etkisinde rol alan molekuler mekanizmalarin aydinlatilmasina yonelmistir. Ancak, hem etki mekanizmalarinin kanser hucre tipine gore farklilik gostermesi hem de biyoyararlanimlarinin sinirli olmasi, biyoyararlanimi arttiracak ve kanser hucre tipine spesifik yaklasimlarin gelistirilmesini gerekli kilmaktadir. Bu derlemede, kurkumin, kuersetin ve cay katesinlerinin yapisal ozellikleri, biyoyararlanimlari, biyolojik etkileri ve anti-kanser etki mekanizmalari tartisilmistir.

The ubiquitin proteasomal system and autophagic pathway are two main protein degradation systems in eukaryotic cells. Inhibition of the proteasomal system with proteasome inhibitors for cancer treatment can cause neurotoxic side effects. In this study, we investigated neurotoxic side effects of bortezomib (BTZ) and carfilzomib (CFZ) in a human neuronal cell model. Inhibition of proteasome with BTZ upregulated autophagy receptor protein p62 level. BTZ caused reduced mitochondrial mass per cell in a greater extent than CFZ. BTZ caused more clustering of mitochondria than CFZ. In conclusion, mitochondrial toxicity and autophagic upregulation with BTZ may be the reason for more severe neurotoxic profile than CFZ.

Flavonoids have chemo-preventive and chemotherapeutic properties against different human cancers including chronic myeloid leukemia. Quercetin and curcumin are two polyphenols with potential anti-carcinogenic and pro-apoptotic properties. We have previously demonstrated the synergistic protective effect of quercetin and curcumin on chronic myeloid leukemia cells (K562) cells. Anti-proliferative and apoptotic effects of these polyphenols were examined by apoptosis and cell viability assays. Oxidative status of the cells was analyzed by determining the level of reactive oxygen species, mitochondrial permeability and intracellular glutathione. Obtained data showed that quercetin and curcumin had beneficial and synergistic effects on K562 cells. On the basis of the above-mentioned data, herein we aimed to clarify signaling pathways involved in synergistic combination of quercetin and curcumin on K562 cells. Normal peripheral blood mononuclear cell line was used as controls. The mRNA and protein expressions of the signaling pathways were detected by Human Signal Transduction Pathway Finder-RT2 PCR Array system and Western blotting, respectively. The results of PCR array were evaluated by DAVID v6.8 and database for KEGG pathways. Our data revealed that synergistic combination of curcumin quercetin was effective on genes that were particularly related to P53, NF and TGF. We believe that our findings will lead to new research in this area and will contribute to the chronic myeloid leukemia treatment protocols.

In this study, we have investigated the antiproliferative effect of quercetin on human papillary thyroid cancer cells and determined the apoptotic mechanisms underlying its actions. We have used different concentrations of quercetin to induce apoptosis and measured cell viability. Apoptosis and cell cycle analysis was determined by flow cytometry using Annexin V and propidium iodide. Finally, we have measured changes in caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP) protein expression levels as hallmarks of apoptosis and Hsp90 protein expression level as a marker of proteasome activity in treated and control cells. Quercetin treatment of human papillary thyroid cancer cells resulted in decreased cell proliferation and increased rate of apoptosis by caspase activation. Furthermore, it was demonstrated that quercetin induces cancer cell apoptosis by downregulating the levels of Hsp90. In conclusion, we have shown that quercetin induces downregulation of Hsp90 expression that may be involved in the decrease of chymotrypsin-like proteasome activity which, in order, induces inhibition of growth and causes cell death in thyroid cancer cells. Thus, quercetin appears to be a promising candidate drug for Hsp90 downregulation and apoptosis of thyroid cancer cells.

Technological developments, changes in consumer behavior and intense competition are the most important threats of today, affecting many sectors as well as the retail industry. Innovative retailers, in the face of with these threats, have embraced and implemented the omni-channel retailing approach, which is the next step in multi-channel. However, other players in the retail industry lag behind this change. The aim of this chapter is to establish the experiences of innovative retailers that have adopted omni-channel retailing in the context of risks, challenges and opportunities. The research data were obtained using questionnaire method from the retailers in Turkey, one of the developing countries. As a result of the study, it was found that retailers who would adopt the omni-channel retailing would have the opportunities to be able to dominate all channels, provide better services to the customers, increase customer satisfaction and loyalty, keep in constant contact with the customers, get better customer recognition and increase sales volume.

Chronic myeloid leukemia is a major hematopoietic malignancy characterized by expansion of myeloid cells. In this study, we have investigated whether quercetin, curcumin and their combination induce apoptosis and inhibit growth of K562 cells. We have observed that quercetin and curcumin combination induced apoptosis accompanied by increased ROS and decreased GSH levels as well as loss of mitochondrial membrane potential. Our mRNA and protein expression results suggested that cytochrome c was released from mitochondria causing PARP and caspase-9 cleavages, the hallmarks of mitochondrial apoptotic pathway. We believe that triggering of apoptosis is mostly via mitochondrial pathway and ROS generation may induce impairment of mitochondrial membrane potential. The use of quercetin and curcumin combination potentiates individual apoptotic effects of the polyphenols and reduces their effective dose thereby preventing potential toxic effects on normal cells. Additional preclinical studies and clinical trials are certainly required to further validate their usefulness as potent anticancer agents.

Whey is used as an additive in food industry and a dietary supplement in nutrition. Here we report a comparative analysis of antioxidant potential of whey and its fractions. Fractions were obtained by size exclusion chromatography, before and after enzymatic digestion with pepsin or trypsin. Superoxide radical scavenging, lipid peroxidation inhibition and cupric ion reducing activities of different fractions were checked. Peptides were detected by SDS-PAGE and GC-MS was used to determine carbohydrate content of the fractions. All samples showed antioxidant activity and the second fraction of the trypsin hydrolysate showed the highest superoxide radical scavenging activity. CUPRAC value of this fraction was two-times higher than that of whey filtrate. The first fraction of the pepsin hydrolysate was the most effective inhibitor of lipid peroxidation. Each sample exhibited a different polypeptide profile. Different percentages of carbohydrates were identified in whey filtrate and in all second fractions, where galactose was the major component. (C) 2013 Elsevier Ltd. All rights reserved.

Backround. Different suture materials are preferable for the repair of Achilles tendon ruptures. The effect of the sutures on the biological level on a repair scenario is still tentative. The purpose of this study is to show the effects of Vicryl (R), Ethibond (R) and PDS (R) II on Achilles tendons at mRNA levels. Methods. 36 Achilles tendons of 18 White New Zealand Rabbit were divided into four groups (n:9). Acute tendon rupture model was created and three groups were repaired with each of the aforementioned sutures (fourth was the control group). At day twelve, mRNA was isolated from each tendon, and expression levels of Collagen (COL) 1A2, COL3A1, Decorin, Matrix Metalloproteinase (MMP) 13 and Interleukin (IL) 1 beta were measured quantitatively and compared. Results. Tendons repaired with PDS (R) II showed high COL1A2, COL3A1 and decorin expression levels (p0.05). Conclusions. Tendons repaired with PDS (R) II are found to have superior properties regarding extracellular matrix component synthesis-degradation, and inflammatory cytokine production at mRNA levels when compared to Vicryl (R) and Ethibond (R). These results can be a guide to surgeons regarding suture choice in Achilles tendon repairs.

Recent studies have shown that whey protein has many useful effects including its anti-cancer effect. In this study we have compared the protective effect of dietary whey protein with whey protein hydrolyzate against azoxymethane and dextran sodium sulfate induced colon cancer in rats. We used a rat model of the colon cancer induced by administration of azoxymethane followed by repeated dextran sodium sulfate ingestion which causes multiple tumor development. Colon tissues were analyzed histologically in addition to biochemical analyses performed by measuring lipid peroxidation, protein oxidation and glutathione levels in both of colon and liver tissues of rats after sacrification. Macroscopic and microscopic tumors were identified in all groups that received azoxymethane followed by repeated dextran sodium sulfate. Group fed with whey protein hydrolyzate showed significantly less macroscopic and microscopic tumor development compared with group fed with whey protein. The protocol applied to generate an appropriate model of colon cancer was successful. Whey protein hydrolyzate was found to be more effective in preventing colon tumor development compared with whey protein.

Proteasomal degradation is an important target in cancer therapy. Many inhibitors have been developed and bortezomib and carfilzomib are used in the clinics. Glioblastoma is a grade IV astrocytoma, and the treatment procedure is radiotherapy and temozolomide combination following surgery. But many cases show drug resistance and recurrence. Recently glioblastoma stem cells, with high protesome activity, were found to be responsible for the drug resistance. In this study, we developed a 3D culture model of glioblastoma and we tested bortezomib and carfilzomib in combination with temozolomide. Hybrid 3D nanofiber scaffold were prepared by electrospinning of core-shell poly(e-caprolactone) (PCL)- bacterial cellulose and PCL- hyaluronic acid. Morphological, surface, and mechanical structure of 3D scaffold were characterized. Attachment of glioblastoma on the scaffold was confirmed by electron microscopy. Temozolomide, bortezomib and carfilzomib treatments were performed on the cell attached scaffolds. Proteasome inhibition, cell viability and apoptosis were tested. Data showed that combination of bortezomib and carfilzomib with temozolomide increased the anti-tumor effects. According to our previous studies, carfilzomib with its lower side effects can be tried in the clinics.

Objective: Dendritic cells (DCs) are members of the mammalian immune system and are considered to be the most powerful antigen presenting cells. They are responsible for the induction of T-cells or T-cell dependent immunity and tolerance. In this study we have investigated the effect of different serum supplements on generation and yield of mature dendritic cells isolated from peripheral blood mononuclear cells.Methods: Three different serum supplements (10% Fetal Bovine Serum, 1% Human Serum Albumin and 1% autologous serum) were compared with serum-free media to identify the role and importance of serum supplements on DC cultivation. Effect of different media on maturation signs (CD40, CD80, CD86, CD209a) and cytokine release (TNF-α, IL-10, IL-12, IL-6) was examined.Results: DCs generated in serum-free media was similar to those of cells in medium with autologous serum. Few dendritic-like cells were observed in fetal bovine serum and human serum albumin. The effect of different media on maturation of DCs was compared phenotypically and increased expression of CD80, CD86 and CD209a identified maturation and yield of DCs.Conclusion: Our results suggest that serum free media can be used to overcome potential drawbacks associated with different serum containing supplements.

Proteasomal degradation is crucial to prevent the accumulation of cellular damage. The removal of the damage is a required process for healthy organisms to keep the integrity while in cancer cells this situation may induce drug resistance. Regarding chemotherapy for the cancer treatment, degradation mechanisms such as proteasomal system and autophagy have been focused recently and proteasomal inhibition in cancer cells have been shown to induce autophagy. This induced pathway may prevent the cancer cells from death or can cause autophagic cell death which is an important reason for chemotherapy resistance. There are many preclinic studies to improve the results and on the other hand heat shock proteins are accepted to be protective which may bring new approach. In our laboratory, several cancer cell lines have been tested from different aspects of proteasomal activity. HCT116 colon cancer cell line was used to test the role of HSP70 and proteasome inhibition on autophagic cell death. In this direction, heat shock treatment has been applied to the cells which is also an applied process for cancer patients. Cell viability, proteasome activity, degradation of long-lived proteins, and the expressions of HSP70, LC3, beclin1, caspase 9 and PARP have been analysed. Additionally, mouse hippocampal cell line is used to test the proteasomal activity in relation to heat shock proteins which highlighted another important point for the chemothrapy resistance with antioxidant gene expressions. Different breast cancer cell lines have also confirmed the role of proteasomal degradation in the failure of chemotherapy. Supported by TUBITAK COST-CM1001-110S281 and TUBITAK 212T156

Kolorektal kanser etiyolojisinde diyetin onemli bir cevresel faktor oldugu yapilan calismalarla kanitlanmistir. Total enerji alimi, yuksek yagli diyet ve kirmizi et alimi ile kolon kanseri gelisimi arasinda baglanti oldugu epidemiyolojik verilerle de desteklenmistir. Bati tarzi diyet ve pisirme teknikleri kolon kanseri icin risk faktoru olarak yer almaktadir. Ote yandan, reaktif oksijen turleri tarafindan olusturulan oksidatif stres, kanser ve norodejeneratif bozukluklar gibi yasa bagli hastaliklarda onemli rol oynamaktadir. Sut serumu proteinleri ve diger diyetsel proteinlerin reaktif oksijen radikallerini temizleme gucune sahip oldugu bildirilmistir. Hayvan calismalarinda karsinojen kullanilarak olusturulan kolon kanserine karsi sut serumu proteinlerinin koruyucu oldugu gosterilmistir. Proteinlerin yaninda protein hidrolizatlarinin da antioksidan aktivite gosterdigi bulunmustur. Protein hidrolizi sirasinda proteinin tersiyer yapisinin bozulmasi ve amino asit salinmasindaki artisa bagli olarak proteinin antioksidan aktivitesinde artis izlenmektedir. Bu derlemede, kolorektal kanser etiyopatogenezindeki mevcut bilgileri ozetlemeye ve tedavide sut serumu proteinlerinin potansiyel kullanimini irdelemeye calistik.

Ağrı her bireyin yaşamının birçok döneminde deneyimlediği bir durumdur. Ağrı süresine göre akut ve kronik ağrı olarak sınıflandırılmaktadır. Ağrının önlenmesinde farmakolojik, nonfarmakolojik ve cerrahi yöntemler uygulanmaktadır. Bu yöntemlerin gerçekleştirilmesinde ve ağrının yönetiminde hemşirelere büyük sorumluluklar düşmektedir. Hemşirelerin uyguladığı non-farmakolojik yöntemlerden biri de dikkati başka yöne çekme stratejisidir. Bu amaçla kullanılan ve son yıllarda ilgi çeken yöntemlerden biri sanal gerçeklik uygulamasıdır. Hem yetişkinlerde hem de pediatrik hastalarda akut ve kronik ağrıyı yönetmek amacıyla sanal gerçeklik yönteminin kullanıldığı araştırmalar yürütülmektedir. Bu nedenle akut ve kronik ağrı yönetiminde dikkati başka yöne çekme yöntemlerinden biri olan sanal gerçeklik uygulamasına yönelik bir değerlendirme yapmak amacıyla bu derleme çalışması gerçekleştirilmiştir., Pain is a condition that every individual experiences at many stages of his life. According to the duration of pain, it is classified as acute and chronic pain. Pharmacological, nonpharmacological and surgical methods are used in the prevention of pain. Nurses have great responsibilities in the realization of these methods and in the management of pain. One of the non-pharmacological methods used by nurses is the distraction strategy. One of the methods used for this purpose and attracting attention in recent years is the virtual reality application. There are researches using virtual reality method to manage acute and chronic pain in both adults and pediatric patients. For this reason, this review study was carried out in order to evaluate the virtual reality application, which is one of the distraction methods to cope with acute and chronic pain.