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Objective Medical laboratories encounter critical obstacles in External Quality Assessment (EQA) practices that are key to assessment of the analytical period. Present study aims to unveil the challenges in nationwide inter-laboratory harmonization and suggest practical solutions. Materials and methods EQA results of 1941 laboratories participating in 18 different EQA-programs between 2010 and 2017 were examined. Standard Deviation Index (SDI) of each program calculated using 801,028 sample data from 24 different clinical chemical tests were used to conduct a process assessment. Results There is a significant discrepancy in unsatisfactory performance ratio among different EAQ-programs with an average of 3.4% (27,074 cases) between 2010 and 2017 and a decreasing trend (~40–50%) in 7-years. Programs with higher SDI display lower discrepancy rates. Reasons for unaccepted results appear to be data entry errors (8.27–22.2%), material dilution errors (5–11.4%), technical problems (3.76–7.9%); while random or unidentified causes account for a major of 44.9–59.5%. In 7-years, 15.7% reduction was observed in average SDI of all tests. Conclusion With the launch of national EQA follow-up program, increased awareness of the analytical processes led to a decrease in unaccepted results and variances in the analytical period. Staff training is suggested as a significant measure. In addition, simultaneous assessment of SDI and allowable total error rates would reduce the variation between programs.

Acute kidney injury (AKI) is a worldwide health problem and defined by rapid loss of excretory function of the kidney with the accumulation of metabolic end products. For effective treatment and prevent complications the early diagnosis of AKI is crucial. The current analytes used to diagnose AKI are not adequately sensitive and specific and therefore clinicians need new biomarkers. One of the new promising biomarker candidates of renal injury is cofilin-1. Previously, in our laboratory we isolated cofilin-1 in kidney preservation solution prior to transplantation and attempted to measure serum cofilin-1 in renal transplanted patients. However, cofilin-1 was not accurately measured in serum samples due to the methodological issues. In this mini-review, we summarized the current knowledge and concepts both in the literature and our experiences with cofilin-1 as a potential biomarker for the diagnosis and management of AKI.

Objective SCUBE1 [signal peptide-CUB (complement C1r/C1 s)-EGF (epidermal growth factor)-like domain-containing protein 1] is a novel biochemical marker. SCUBE1 is thought to play roles both in platelet activation and inflammation, which are important stages for the development of acute ischemic stroke (AIS).The purpose of our study was to determine the diagnostic and prognostic values and temporal change of plasma SCUBE1 levels in AIS patients. Materials and methods Thirty-five patients diagnosed with AIS at the Cumhuriyet University Faculty of Medicine Neurology Department, between June and December 2017, and a control group of 35 healthy volunteers were included. Results Median first day SCUBE1 value in the patient group was 97.51 ng/mL, and the median 7th day SCUBE1 value was 32.72 ng/mL. Median control group SCUBE1 value was 27.51 ng/mL. The first day SCUBE1 levels were significantly higher than the 7th day and the control group SCUBE1 levels (p=0.001, p<0.001, respectively). The ROC analysis showed that SCUBE1 levels above 68.8 ng/mL can be used as an indicator with high sensitivity and specificity for AIS diagnosis. Multivariate analysis revealed that the first day SCUBE1 had significant independent effects on development of AIS. In correlation analysis, plasma SCUBE1 levels showed a significantly positive correlation with lesion volume, NIHSS and MRS values (p<0.01). Conclusion First day plasma SCUBE1 values in AIS patients rised at significant levels compared to the control group. SCUBE1 could use both in the early diagnosis and prediction of prognosis and lesion volume of AIS patients.

Objective In this study, our aim was to investigate the clinical significance of VEGF, sVEGFR-1 in HFpEF patients. Materials and methods Seventy-two participants enrolled in this cross-sectional case-control study including HFpEF patients (n=41) and healthy (n=31) subjects. Blood samples were collected and serum VEGF, sVEGFR-1 analysis, and transthoracic echocardiography were performed. Results and discussion The average sVEGFR-1 level of HFpEF patient group was significantly higher than the control group (respectively 0.136 ng/L (0.04–0.34), 0.06 ng/L (0.01–0.25); p<0.001). The average VEGF level of HFpEF patients using beta blocker was significantly higher than the HFpEF patients not using it (respectively 0.585±0.194 ng/L; 0.349±0.269 ng/L; p=0.025). The average VEGF level of HFpEF patients using statins was significantly higher than the HFpEF patients without a medication (respectively 0.607±0.099 ng/L; 0.359±0.273 ng/L; p=0.038). Conclusion Our study is the first study demonstrating the relations among HFpEF, accompanying morbidities, VEGF and sVEGFR-1 levels. Statins and beta blockers may have positive effects on angiogenesis in HFrEF patients via increasing VEGF levels.

Background Autologous platelet rich plasma (PRP) is the platelet concentration obtained from thrombocytes in the plasma. During the healing process, the platelets are activated and then release the granules which stimulate the inflammatory cascade and healing process. Platelet derived growth factor, vascular endothelial growth factor (VEGF), transforming growth factor β (TGFβ), epidermal growth factor (EGF) and fibroblast growth factor (FGF) are valuable markers used for cell regeneration. The aim of this study was to investigate the potential effects of PRP treatment on the neomucosa formation, a potential technique for increasing the intestinal surface area in patients with short bowel syndrome (SBS). Materials and methods Thirty-two male Wistar-Hannover rats were divided into: sham, control, PRP-treated and last group for PRP preparation (n=8). Plasma levels of VEGF, TGFβ, EGF and FGF were quantified by ELISA. En-bloc resection of anastomotic part was performed and stained with hematoxylin-eosin. Results VEGF, FGF, TGFβ and EGF levels were found significantly increased in PRP-treated group compared to others (p<0.001). Neomucosa formation was observed in experimental groups but the area increased significantly in PRP group, compared to other groups (p<0.001). Conclusion PRP therapy in gastrointestinal anastomoses is truly beneficial and surgically applicable treatment in SBS patients.

Background IVSII-74 T > G is one of the most frequently identified polymorphic sites on the β-globin gene. In our report, we present three cases with low mean corpuscular volume (MCV) value in three and high red blood cell (RBC) value in two of the cases. The objective of this study was to further analyse the reason for condition of three patients, who were referred for the investigation of persistent anemia. Materials and Methods Following the HPLC analyses of Hb migration pattern, direct nucleotide sequencing of α- and β-globin genes was performed for all cases. Results The common finding was the homozygosity for the intronic change, IVSII-74 T > G. Conclusion In the intersection point of the variations on our patients, we claim a homozygous change at position 74 on the intron II of the β-globin gene alone may be sufficient to cause a β-thalassemia carrier phenotype.

Background Potential targets for prostate cancer therapy are urgently needed for curative of patients. Cyclosporine-A (CsA), an immunosuppressive and a selective cyclooxygenase-2 (COX-2) inhibitor, exerts antitumor activity. However, the molecular effects of CsA is not fully understood in prostate cancer. In this research, we sought to determine role and mechanism of CsA in prostate cancer. Materials and methods PC3 and DU145 cells were treated with CsA time (12, 24, 48 h) and dose dependent (2.5, 10, 25 μM) and cell survival, migration, colony formation, expression of apoptosis related proteins/genes using MTT assay, scratch assay, Western blotting/qPCR. At the same time, cells treated with CsA to test on the effects of COX-2 promoter activity using luciferase reporter plasmid. Lastly, functional role in the CsA treatment prostate cancer cells were interrogated for relationship of TGFβ, Akt, caspases and COX-2. Results These study findings provided direct evidences that the CsA induced apoptosis and downregulated migration. Conclusions CsA downregulated Akt as well as COX-2 and upregulated TGFβ, resulting in the suppression of cell migration which was augmented a potential therapeutic of CsA in prostate cancer cells.

Background Today, there is a growing recognition in the scientific community of the many roles of butyrylcholinesterase (BChE) in both physiological and pathological contexts. Objective Here, we aim at providing an accurate and comprehensive understanding of the mechanistic and structural aspects of mammalian BChE inhibition by the tricyclic antidepressant amitriptyline (AMI). Materials and methods The present work involves enzyme kinetic studies as well as protein–ligand docking and interaction profiling studies. Results We verify that AMI acts as an effective, mixed-type inhibitor of mammalian BChE, with an IC 50 value of 10 μM and a K i value of 2.25 μM. We also provide evidence showing that AMI penetrates deep into the active-site gorge of BChE where it interacts noncovalently with both the choline-binding and catalytic residues. Conclusion These findings could facilitate the prevention of the adverse metabolic sequelae of acquired BChE deficiency and also the design of new reversible anticholinesterase drugs.

Background Malignant mesothelioma (MM) is an endemic disease around central Anatolia region in Turkey, where people are exposed to erionite- and asbestos-contaminated soil. Aberrant EGFR signalling has implicated in several cancers including MMs. Tyrosine kinase inhibitors are new treatment options harbouring deregulated signalling network components. In this study, we aimed to investigate anti-proliferative effect of CL-387,785 in MM cells. Materials and methods Alteration of cell proliferation was evaluated with using MTS assay. Profile of EGFR, ERK, AKT, JNK and p38 proteins and ELK-1, JUN, STAT1, STAT3 and STAT5 genes were analysed by western blot and RT-PCR, respectively. Results Viability of MM cells was inhibited in dose- and time-dependent manner. CL-387,785 affected MM cells earlier and at higher extent compared to the mesothelial cells. CL-387,785 treatments suppressed EGF-induced phosphorylation of EGFR, ERK, AKT, STAT3 and STAT5 but not SAPK/JNK and p38 in SPC212 cells. RT-PCR analysis showed that expression of p21 increased, while Cyclin D and c-jun expressions decreased in SPC212 cells. However, ELK-1, STAT3 and STAT5, expressions did not change. Conclusion Our results propose that CL-387,785 could be an efficacious agent in the treatment of MMs with uncontrolled EGFR signalling.

Background Therapeutic options for advanced cholangiocarcinoma (CCA) are limited and ineffective due to the largely incomplete understanding of the molecular pathogenesis of this deadly tumor. So that, we planned to investigate epigenetic regulation of epithelial-mesenchymal transition (EMT) in cholangiocarcinoma cell line by applying Suberoylanilide hydroxamic acid (SAHA). We studied the effect of SAHA on cell proliferation, colony forming, migration and protein level of E-cadherin (E-cad) as an epithelial EMT marker, N-cadherin (N-cad) and Vimentin (Vim), as a mesenchymal markers of EMT, in human CCA cell line. Materials and methods Cell proliferation and migration measurements were performed by flow cytometry and wound healing assay, respectively. E-cad, N-cad and Vim protein levels were determined by Western blot analysis. Results It was found that SAHA significantly inhibits cell viability, proliferation and migration of TFK-1 cells, accompanied by reversing of EMT markers. SAHA, upregulated protein level of E-cad, while downregulated the protein levels of N-cad and Vimentin. Conclusions SAHA treatment may bebeneficial for CCA patients and SAHA might be a potential therapeutic agent for the treatment of CCA. However, future studies are needed to evaluate the clinical applicability of SAHA as a part of the chemotherapeutic regimen for CCA.

Objective Investigation of the anticarcinogenic effects of natural products with low toxicity is very important in the development of new therapeutic strategies against cancer. Ginnalin A (GA) is one of the most important phenolic compounds of Acer genus and its anticancer effect has been shown that in various cancer cell lines. SB203580, a p38 MAPK inhibitor, can inhibit cell proliferation independently of p38 MAPK. The objective of this study was to investigate combination effect of GA and SB203580 on Hep-3B cell line. Material and methods Cell viability was determined by using XTT method after the treatment with GA, SB203580 and combination of both. Anticarcinogenic effects of GA and SB203580 both in single and in combination have been analyzed with Caspase-3 activity assay and expression levels of important genes involved in cell cycle and apoptosis were evaluated by qPCR. Results GA and SB203580 have shown additive effect on Hep-3B cells in the combination inhibited 50% of cell viability. And, SB203580 increased the effect of GA on activation of Caspase-3 and expressions of genes important in apoptosis and cell cycle. Conclusion This study indicates that GA and SB203580 can be an effective for development of new therapeutic strategies in hepatocellular carcinoma.

Background Comparing gene expression profiles using gene expression datasets of different types of tumors is frequently used to identify molecular mechanisms of cancer. This study aimed to find shared and type specific gene expression profiles of hepatocellular carcinoma (HCC) and B-cell chronic lymphocytic leukemia (B-CLL). Material and methods Gene expression microarrays for HCC and B-CLL and RNA-sequencing expression data for liver HCC and lymphoid neoplasm diffuse large B-cell lymphoma (DLBC) were analyzed and differentially expressed probe sets or genes for each cancer type were detected. Probe sets and genes that were shared or specifically expressed in both cancer types were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) terms for Biological Process (BP) annotations were performed. Results According to our analysis shared upregulated genes were mainly annotated in cell cycle processes. Some of the genes that changed only in HCC were annotated in cell cycle and metabolic processes, and some of the genes, altered only in B-CLL, were annotated in immune response and hemopoiesis. Conclusion These results contribute to cancer research that aim to find the conserved gene expression profiles in different cancer types and widen the knowledge of HCC and B-CLL specific mechanisms.

“Glycans”, which are generally referred as oligosaccharides and polysaccharides, are structures that are present on all cellular surfaces with proteins and lipids being attached to their basic chain structures. Many studies in the field of glycobiology have identified the various and complicated biological roles of these glycans which make them perfect molecules to use in labelling and selecting body cells specifically. This study aims at analyzing the modifications in saccharide units of glycans on a cell membrane surfaces of the pancreatic tissue of rats to which normal and metabolic syndrome (MetS) are established. To this end, a MetS model was created through a high fructose diet in Spraque Dawley breed of rats and the pancreatic tissue sections of the group with MetS and control group animals were evaluated comparatively. The targeted saccharide units were examined with Fluorescent Microscope by using two different Fluorescein (FITC) labelled lectins, namely Maackia amurensis-1 lectin [FITC-(MAL-I)] and the Wheat Germ Agglutinin (FITC-WGA). It was observed that FITC-MAL-1-labelled Galβ4GlcNAc units did not change much due to high- fructose diet. On the other hand, more GlcNAc, Neu5Ac and β-GlcNAc units which are labelled with FITC-WGA lectin increase in numbers in pancreatic sections of high fructose diet, compared to control group. Thus, a rapid and specific labelling method, which can identify surface saccharide sequences specifically, was developed. The method can be used in early diagnosis and/or treatment for metabolic diseases.

Background: Hyperprolactinemia is one of the most common endocrine disorders of the hypothalamic-pituitary axis. Hyperprolactinemia and galactorrhea are rarely seen as adverse effects of antidepressant drugs. Case presentation: Thirty-three years old women, between 2011 and 2017, three depressive episodes were observed. Initially, fluoxetine was used, no galactorrhea was detected. Secondly, she was given escitalopram and visited the clinic with amenorrhea and galactorrhea. Her serum prolactin levels were 50.88 ng/mL and MRI findings were normal. Escitalopram was discontinued and prescribed cabergoline and then prolactin levels were 16.56 ng/mL in the third month. During the vortioxetine treatment, she developed galactorrhea and prolactin level was 43.65 ng/mL. Vortioxetine was discontinued and it was measured at 20.14 ng/mL after 4 weeks of drug-free observation. Conclusion: Vortioxetine is a multimodal agent that modulates a select population of 5-HT receptors. To literature, there was no case presentation of galactorrhea observed during the use of vortioxetine. Galactorrhea associated with SSRIs are limited to case presentations. Antidepressants are thought to cause galactorrhea through tuberoinfundibular dopaminergic neurons or postsynaptic serotonergic neurons in the hypothalamus. When galactorrhea was observed during antidepressant drug use, prolactin levels and MRI should be investigated, and termination/replacement of antidepressant treatment is recommended if necessary.

Objective Decreased unconjugated estriol (uE3) concentrations increase calculated risk of Down syndrome. Therefore, falsely low uE3, due to assay interference, have the potential to cause false-positive screening results. Here we present a 35 years old woman with a pregnancy of 17+2 weeks. Materials and methods Second-trimester screening test was performed on the UniCelDxI 800 (Beckman Coulter, Brea, CA, USA) analyzer and her uE3 level was 0.21 ng/mL (0.21 MoM). Risk calculated for DS was 1/8. Measurements were repeated on IMMULITE 2000 XPi (Siemens Healthcare Diagnostics Inc., USA). uE3 result was 0.614 ng/mL (0.97 MoM). The risk for DS was negative with this system. There was no sign of fetal anomaly on three-dimensional ultrasound examination and cell-free fetal DNA screening test. We suspected assay interference for uE3. Results Serial dilutions of serum samples revealed nonlinearity. 36.3% increase was observed with heterophile antibody blocking tubes. The post-polyethylene glycol treatment resulted approximately the same uE3 levels as IMMULITE system. Addition of alkaline phosphatase Scavenger to serum increased the result by 90% showing that falsely low E3 result was due to an interferent reacting on assay medium. Conclusion Laboratories should be aware that falsely low uE3 results due to interference may be obtained.

Objective Statins and Paracetamol have widespread use in clinic and both drugs possess similar side effects; therefore, we investigated if drug-interaction occurs when the combination of these two drugs is used during therapy. Materials and methods A total of 32 (12–15 months old) grown-up male rats were divided into four groups: Control group, RSV group (10 mg/kg Rosuvastatin/daily), APAP group (50 mg/kg Paracetamol/5 days/weekly), RSV+APAP (10 mg/kg Rosuvastatin/daily+50 mg/kg Paracetamol/5 days/weekly). At the end of 8 weeks of chronic treatment, the blood and tissue samples were taken under the Ketamine and Xylasine anesthesia (50 mg/kg and 5 mg/kg, respectively). Results In the liver, sinusoidal dilatations, pyknotic nuclei and hemorrhagic foci are more frequently seen in the group receiving combination therapy; although serum liver functions among groups were not significantly different. Kidney histopathologic alterations in APAP and RSV+APAP groups were found more distinct than in RSV alone group. Inducible nitric oxide synthase activity was highly increased with combination therapy in liver and kidney tissues. Conclusion RSV-Paracetamol interaction may occur as an important drug interaction histopathologically even before it is manifested biochemically in the clinic.