Bosnian Journal of Basic Medical Sciences <p>The Bosnian Journal of Basic Medical Sciences (BJBMS) is an international, English-language, peer-reviewed journal, publishing articles in different disciplines of basic medical sciences. BJBMS welcomes original research and comprehensive reviews as well as short research communications in the field of molecular biology, biochemistry, genetics, immunology, microbiology, pathology, pharmacology, pharmaceutical sciences, physiology and translational research.</p> Association of Basic Medical Sciences of FBIH en-US Bosnian Journal of Basic Medical Sciences 1512-8601 <p>© Association of Basic Medical Sciences of FBIH.</p> Internodal HER2 heterogeneity of axillary lymph node metastases in breast cancer patients <p>Determination of human epidermal growth factor receptor 2 (HER2) status is important for adequate treatment of breast cancer (BC) patients. The novel HER2 gene protein assay (GPA) is particularly convenient, as it allows the simultaneous assessment of HER2 protein expression and gene amplification at individual cell level. Here we investigated the frequency of internodal HER2 heterogeneity in axillary lymph node macrometastases of BC patients and compared HER2 status between primary breast tumor and its metastases. We included a total of 41 female patients operated between 2014 and 2015 for primary BC with axillary lymph node macrometastases. Representative paraffin blocks of metastatic lymph nodes were sectioned and the slides were stained using the GPA in 38 BC cases. GPA results were assessed according to the ASCO/CAP 2013 criteria. We analyzed 12586 individual tumor cells, 120 cells per section of each metastatic lymph node. HER2 status differed between the primary tumor and its metastases in 5/38 cases (13.2%). In patients with at least two metastatic nodes, the HER2 status of lymph node metastases was only slightly different in 4/23 cases (17.4%). Our results indicate rare but substantial differences in HER2 status between primary breast tumor and its axillary lymph node metastases that may direct the choice and outcomes of targeted therapy in BC patients. The impact of the rare and subtle internodal HER2 heterogeneity evidenced in this study remains uncertain. Determining the HER2 status of lymph node metastases in BC seems to be rational, but assessing a limited number of metastatic nodes may be sufficient.</p> Ilija Vladimir Baroš Nataša Tanasković Ulrika Pellas Živka Eri Ljiljana Tadić Latinović Tibor Tot Copyright (c) 2019 Bosnian Journal of Basic Medical Sciences 2019-08-20 2019-08-20 19 3 242 248 10.17305/bjbms.2019.3970 Expression patterns and prognostic value of miR-210, miR-494, and miR-205 in middle-aged and old patients with sepsis-induced acute kidney injury <p>Septic patients suffer a ‘cytokine storm’ from proinflammatory cytokines, chemokines and other inflammatory mediators, resulting in acute kidney injury (AKI) and death. The purpose of the present study was to determine the expression patterns of microRNA-210 (miR-210), miR-494, and miR-205 in middle-aged and old patients with sepsis-induced AKI and to evaluate their association with patient prognosis. Serum blood urea nitrogen (BUN), creatinine (Cr) and cystatin C levels were determined in peripheral venous blood collected from 110 patients with sepsis-induced AKI and 110 healthy controls. The expression profile of 30 miRNAs was analyzed by TaqMan low-density array (TLDA) in plasma samples from patients and controls. Association of miRNAs with prognosis and survival of patients was analyzed by Spearman’s rank correlation coefficient, Cox multivariate analysis, and ROC curve analysis. TILDA analysis showed 11 upregulated and 11 downregulated miRNAs in patients with sepsis-induced AKI. MiR-210 and miR-494 were the most upregulated and miR-205 was the most downregulated miRNA. High expression of miR-210 and miR-494 was positively correlated with BUN, Cr and cystatin C levels of patients, while low expression of miR-205 was negatively correlated. MiR-210 and miR-494 expression was significantly decreased and miR-205 expression was increased in survivors with sepsis-induced AKI (28-day survival, n = 68) vs. non-survivors (n = 42). BUN, Cr, and miR-205 were independent risk factors for prognosis in sepsis-induced AKI. Our study showed the predictive value of miR-210, miR-494, and miR-205 in prognosis and survival of patients with sepsis-induced AKI. MiR-205 is an independent risk factor for sepsis-induced AKI and its decreased expression is associated with shorter patient survival.</p> Yongjun Lin Ying Ding Shuping Song Man Li Tao Wang Feng Guo Copyright (c) 2019 Bosnian Journal of Basic Medical Sciences 2019-08-20 2019-08-20 19 3 249 256 10.17305/bjbms.2019.4131 Thymic stromal lymphopoietin levels are increased in patients with celiac disease <p>Thymic stromal lymphopoietin (TSLP) is a cytokine produced by epithelial cells in the lungs, skin, and intestinal mucosa and is involved in several physiological and pathological processes. In this study, we evaluated serum TSLP levels in patients with celiac disease (CD). The prospective study was conducted at a gastroenterology outpatient clinic between March 2018 and August 2018. Eighty-nine participants aged between 18 and 75 years were classified into following groups: 22 patients with newly diagnosed CD; 20 patients with CD who were compliant with a gluten-free diet (GFD); 32 patients with CD who were not compliant with a GFD; and 15 healthy controls. Demographic characteristics, disease duration, and selected biochemical and hematologic parameters were recorded and compared between groups. Median serum TSLP levels were 1193.65 pg/mL (range: 480.1–1547.1) in newly diagnosed CD patients, 110.25 pg/mL (range: 60.3–216.7) in CD patients who were compliant with a GFD, 113.1 pg/mL (range: 76.3–303.4) in CD patients who were not compliant with a GFD, and 57 pg/mL (range: 49–67.8) in healthy controls. Overall, there was a significant difference in serum TSLP levels between groups (<em>p</em> = 0.001). Patients with newly diagnosed CD had the highest serum TSLP levels. There was no significant difference in serum TSLP levels between patients with CD who were and were not compliant with a GFD. TSLP appears to be involved in the pathogenesis of CD. Further studies are required to determine if the TSLP signaling pathway can be used in the treatment of CD.</p> Evrim Kahramanoğlu Aksoy Muhammet Yener Akpınar Ferdane Pirinççi Sapmaz Özlem Doğan Metin Uzman Yaşar Nazlıgül Copyright (c) 2019 Bosnian Journal of Basic Medical Sciences 2019-08-20 2019-08-20 19 3 282 287 10.17305/bjbms.2019.4016 Epidemiology and mechanism of drug resistance of Mycoplasma pneumoniae in Beijing, China: A multicenter study <p><em>Mycoplasma pneumoniae</em> (<em>M. pneumoniae</em>) is one of the most common causes of community-acquired respiratory tract infections (RTIs). We aimed to investigate the prevalence of <em>M. pneumoniae </em>infection, antibiotic resistance and genetic diversity of <em>M. pneumoniae</em> isolates across multiple centers in Beijing, China. P1 protein was detected by Nested PCR to analyze the occurrence of <em>M. pneumoniae </em>in pediatric patients with RTI. <em>M. pneumoniae</em> isolates were cultured and analyzed by Nested-PCR to determine their genotypes. Broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of antibiotics. Out of 822 children with RTI admitted to 11 hospitals in Beijing, 341 (41.48%) were positive for <em>M. pneumoniae</em> by Nested PCR and 236 (69.21%) samples had mutations in 23S rRNA domain V. The highest proportion of <em>M. pneumoniae </em>positive samples was observed in school-age children (118/190; 62.11%) and in pediatric patients with pneumonia (220/389; 56.56%). Out of 341 <em>M. pneumoniae</em> positive samples, 99 (12.04%) isolates were successfully cultured and the MIC values were determined for 65 <em>M. pneumoniae</em> strains. Out of these, 57 (87.69%) strains were resistant to macrolides, and all 65 strains were sensitive to tetracyclines or quinolones. <em>M. pneumoniae</em> P1 type I and P1 type II strains were found in 57/65 (87.69%) and 8/65 (12.31%) of cultured isolates, respectively. Overall, we demonstrated a high prevalence of <em>M. pneumoniae </em>infection and high macrolide resistance of<em> M. pneumoniae </em>strains in Beijing. School-age children were more susceptible to<em> M. pneumoniae</em>, particularly the children with pneumonia. Thus, establishment of a systematic surveillance program to fully understand the epidemiology of <em>M. pneumoniae</em> is critical for the standardized use of antibiotics in China.</p> Dong-Xing Guo Wen-Juan Hu Ran Wei Hong Wang Bao-Ping Xu Wei Zhou Shao-Jie Ma Hui Huang Xuan-Guang Qin Yue Jiang Xiao-Pei Dong Xiao-Yan Fu Da-Wei Shi Liang-Yu Wang A-Dong Shen De-Li Xin Copyright (c) 2019 Bosnian Journal of Basic Medical Sciences 2019-08-20 2019-08-20 19 3 288 296 10.17305/bjbms.2019.4053 EP1 receptor is involved in prostaglandin E2-induced osteosarcoma growth <p>Recent studies showed that the activation of prostaglandin (PG) receptor EP1 promotes cell migration and invasion in different cancers. The aim of this study was to investigate the role of EP1 in the proliferation of osteosarcoma (OS) cells <em>in vitro</em> and <em>in vivo</em>. EP1 mRNA and protein levels were analyzed by real-time RT-PCR and Western blot, respectively in human OS cell lines MG63, OS732, U-2OS, and 143B compared to human fetal osteoblastic hFOB 1.19 cells. MG63 cells were treated with PGE<sub>2</sub>, EP1 specific agonist 17-PT-PGE<sub>2</sub>, 17-PT-PGE<sub>2</sub> + EP1 specific antagonist SC51089, or DMSO (control). EP1R-siRNA or a non-silencing irrelevant RNA duplex (negative control) were used for the transfection of MG63 cells, followed by PGE<sub>2</sub> treatment. Nude mice carrying MG63 xenografts were treated with SC51089 (2 mg/kg/day). MG63 cells/xenografts were analyzed by MTT assay, TUNEL assay, PKC enzyme activity assay, and Western blot (EP1 and apoptotic proteins), and tumor growth/volume was evaluated in mice. EP1 levels were significantly higher in OS cells compared to osteoblasts. PGE<sub>2</sub> or 17-PT-PGE<sub>2</sub> treatment increased the proliferation and decreased the apoptosis of MG63 cells. Inhibition of EP1 by SC51089 or siRNA markedly decreased the viability of MG63 cells. Similarly, SC51089 treatment significantly inhibited MG63 cell proliferation and promoted apoptosis <em>in</em> <em>vivo</em>. The silencing of EP1 receptor by siRNA or blockade of EP1 signaling by SC51089 activated extrinsic and intrinsic apoptotic pathways both <em>in</em> <em>vivo</em> and <em>in</em> <em>vitro</em>, as evidenced by increased levels of Bax, cyt c, cleaved caspase-3, caspase-8 and caspase-9. EP1 appears to be involved in PGE<sub>2</sub>-induced proliferative activity of MG63 cells. Antagonizing EP1 may provide a novel therapeutic approach to the treatment of OS.</p> Jing-cai Niu Nan Ma Wei Liu Pei-ji Wang Copyright (c) 2019 Bosnian Journal of Basic Medical Sciences 2019-08-20 2019-08-20 19 3 265 273 10.17305/bjbms.2019.4177 Isoflurane exposure in infant rats acutely increases aquaporin 4 and does not cause neurocognitive impairment <p>Isoflurane is commonly used in pediatric population, but its mechanism of action in cognition is unclear. Aquaporin 4 (AQP4) regulates water content in blood, brain, and cerebrospinal fluid. Various studies have provided evidence for the role of AQP4 in synaptic plasticity and neurocognition. In this study, we aimed to determine whether a prolonged exposure to isoflurane in infant rats is associated with cognition and what effect this exposure has on AQP4 expression. Ten-day-old [postnatal day (P) 10] Wistar albino rats were randomly allocated to isoflurane group (n = 32; 1.5% isoflurane in 50% oxygen for 6 hours) or control group (n = 32; only 50% oxygen for 6 hours). Acute (P11) and long-term (P33) effects of 6-hour anesthetic isoflurane exposure on AQP4 expression were analyzed in whole brains of P11 and P33 rats by RT-qPCR and Western blot. Spatial learning and memory were assessed on P28 to P33 days by Morris Water Maze (MWM) test. The analysis revealed that isoflurane increased acutely both mRNA (~4.5 fold) and protein (~90%) levels of AQP4 in P11 rats compared with control group. The increasing levels of AQP4 in P11 were not observed in P33 rats. Also, no statistically significant change between isoflurane and control groups was observed in the latency to find the platform during MWM training and probe trial. Our results indicate that a single exposure to isoflurane anesthesia does not influence cognition in infant rats. In this case, acutely increased AQP4 after isoflurane anesthesia may have a protective role in neurocognition.</p> Serdar Demirgan Onat Akyol Zeynep Temel Aslıhan Şengelen Murat Pekmez Recep Demirgan Mehmet Salih Sevdi Kerem Erkalp Ayşin Selcan Copyright (c) 2019 Bosnian Journal of Basic Medical Sciences 2019-08-20 2019-08-20 19 3 257 264 10.17305/bjbms.2019.4116 PCAT1 is a poor prognostic factor in endometrial carcinoma and associated with cancer cell proliferation, migration and invasion <p>Long non-coding RNAs (lncRNAs) are emerging as important modulators of cancer progression, among which prostate cancer-associated transcript 1 (PCAT1) has been shown to be an oncogene in several tumors. However, the clinical significance and biological function of PCAT1 in endometrial carcinoma (EC) remain unclear. In this study, we used 89 EC tissues and HEC-1B, Ishikawa, RL95-2 and AN3CA EC cell lines. We found elevated expression levels of PCAT1 in EC tissues and cell lines using reverse transcription qPCR (RT-qPCR). The prognostic value of PCAT1 was determined using Kaplan–Meier survival and Cox regression analysis. The results showed that higher PCAT1 expression was positively correlated with FIGO stage, myometrial invasion, lymph node metastasis, and a shorter overall survival. A series of functional assays showed that the knockdown of PCAT1 by small interfering RNA (siRNA) targeting PCAT1 (siPCAT1) suppressed cell proliferation, migration and invasion, but promoted apoptosis. Western blot analysis further showed that B-cell lymphoma 2 (Bcl-2), vimentin and N-cadherin were downregulated, but E-cadherin and Bcl-2-associated death promoter (Bad) were upregulated in PCAT1-silenced EC cells. Taken together, our results underscore the oncogenic role of PCAT1 in EC and show that PCAT1 may be a potential therapeutic target in EC treatment.</p> Xiaohuan Zhao Yali Fan Changqiong Lu Hongfang Li Ning Zhou Gaogao Sun Hong Fan Copyright (c) 2019 Bosnian Journal of Basic Medical Sciences 2019-08-20 2019-08-20 19 3 274 281 10.17305/bjbms.2019.4096 Valspodar-modulated chemotherapy in human ovarian cancer cells SK-OV-3 and MDAH-2774 <p>Overcoming drug resistance in ovarian cancer is the overarching goal in gynecologic oncology. One way to increase drug cytotoxicity without increasing the drug dose is to simultaneously apply multidrug resistance modulator. Valspodar is the second generation P-glycoprotein 1 modulator capable of reversing multidrug resistance in different cancers. In this study, we evaluated the effect of valspodar and cisplatin co-treatment on cell viability, cell death and oxidative status in ovarian cancer cells. Two human ovarian cancer cell lines SK-OV-3 and MDAH-2774 were treated with cisplatin, valspodar, or cisplatin + valspodar for 24 or 48 hours. Untreated cells were used as control group. Cell viability was evaluated by MTT assay. Cell death was assessed by TUNEL and comet assay. Lipid peroxidation (malondialdehyde) and protein thiol groups were analyzed as oxidative stress markers. The expression of mitochondrial superoxide dismutase (MnSOD) was assessed by immunocytochemistry. Valspodar effectively reduced the resistance of SK-OV-3 cells to cisplatin, as demonstrated by increased oxidative stress, decreased cell viability and increased apoptosis in SK-OV-3 cells co-treated with valspodar and cisplatin compared to other groups. However, valspodar did not significantly affect the resistance of MDAH-2774 cells to cisplatin. Stronger staining for MnSOD in MDAH-2774 vs. SK-OV-3 cells after co-treatment with cisplatin and valspodar may determine the resistance of MDAH-2774 cell line to cisplatin.</p> Maciej Zalewski Julita Kulbacka Jolanta Saczko Małgorzata Drag-Zalesinska Anna Choromanska Copyright (c) 2019 Bosnian Journal of Basic Medical Sciences 2019-08-20 2019-08-20 19 3 234 241 10.17305/bjbms.2019.4073 How latent viruses cause breast cancer: An explanation based on the microcompetition model <p>Most breast cancer cases show a decrease in the concentration of the breast cancer type 1 susceptibility protein (BRCA1). However, only a small portion of these cases have a mutated <em>BRCA1</em> gene. Although many attempts have been made to identify the reason for the decrease in BRCA1 concentration in sporadic, non-heritable breast cancer cases, the cause is still unknown. In this review, we use the Microcompetition Model to explain how certain latent viruses, which are frequently detected in breast cancer tumors, can decrease the expression of the <em>BRCA1</em> gene and cause the development of breast tumors.</p> Hanan Polansky Hava Schwab Copyright (c) 2018 Bosnian Journal of Basic Medical Sciences 2019-08-20 2019-08-20 19 3 221 226 10.17305/bjbms.2018.3950 Review of the therapeutic neurofeedback method using electroencephalography: EEG Neurofeedback <p>Electroencephalographic neurofeedback (EEG-NFB) represents a broadly used method that involves a real-time EEG signal measurement, immediate data processing with the extraction of the parameter(s) of interest, and feedback to the individual in a real-time. Using such a feedback loop, the individual may gain better control over the neurophysiological parameters, by inducing changes in brain functioning and, consequently, behavior. It is used as a complementary treatment for a variety of neuropsychological disorders and improvement of cognitive capabilities, creativity or relaxation in healthy subjects. In this review, various types of EEG-NFB training are described, including training of slow cortical potentials (SCPs) and frequency and coherence training, with their main results and potential limitations. Furthermore, some general concerns about EEG-NFB methodology are presented, which still need to be addressed by the NFB community. Due to the heterogeneity of research designs in EEG-NFB protocols, clear conclusions on the effectiveness of this method are difficult to draw. Despite that, there seems to be a well-defined path for the EEG-NFB research in the future, opening up possibilities for improvement.</p> Nina Omejc Bojan Rojc Piero Paolo Battaglini Uros Marusic Copyright (c) 2018 Bosnian Journal of Basic Medical Sciences 2019-08-20 2019-08-20 19 3 213 220 10.17305/bjbms.2018.3785 Targeted immunotherapy with a checkpoint inhibitor in combination with chemotherapy: A new clinical paradigm in the treatment of triple-negative breast cancer <p>The treatment of several solid and hematologic malignancies with immune checkpoint inhibitors (against programmed death receptor-1/ligand-1 [PD-1/PD-L1]) has dramatically changed the cancer treatment paradigm. However, no checkpoint inhibitors were previously approved for the treatment of triple-negative breast cancer (TNBC), a difficult-to-treat disease with a high unmet therapeutic need. Based on IMpassion130 clinical trial (NCT02425891), the Food and Drug Administration (FDA) has recently granted an accelerated approval for atezolizumab (TECENTRIQ®), a monoclonal antibody drug targeting PD-L1, plus chemotherapy (Abraxane; nab®-Paclitaxel) for the treatment of adults with PD-L1-positive, unresectable, locally advanced or metastatic TNBC. The FDA has also approved the Ventana diagnostic antibody SP142 as a companion test for selecting TNBC patients for treatment with atezolizumab. In the present review, we briefly discuss the importance of this breakthrough as the first cancer immunotherapy regimen to be approved for the management of breast cancer.</p> Farhan S. Cyprian Saghir Akhtar Zoran Gatalica Semir Vranic Copyright (c) 2019 Bosnian Journal of Basic Medical Sciences 2019-08-20 2019-08-20 19 3 227 233 10.17305/bjbms.2019.4204 The 2019 measles epidemic in Bosnia and Herzegovina: What is wrong with the mandatory vaccination program? <p>Measles is a highly contagious and communicable viral disease which may be prevented by a sustained vaccination program. Due to missed vaccination, two major epidemics of measles (1997–1999 and 2014–2015) have been recorded after the war in Bosnia and Herzegovina (BH) with over 10,000 patients registered. According to the World Health Organization, BH is categorized as a country with endemic transmission of measles. The last measles epidemic was between 2014 and 2015, with 5,083 documented patients in the Federation of BH. In the first four months of 2019, more than 700 measles cases were registered in the same region. Significant transmission rate has been observed in Sarajevo Canton (SC) with 570 documented measles cases. Out of 570 measles cases in SC, 92.5% were unvaccinated. The most affected were children up to 6 years of age (62.8%), with one documented case of death (7-month old infant). In addition to this report, we discussed key stakeholders and possible circumstances responsible for the epidemic. The measles epidemic is still ongoing.</p> Jurica Arapović Željana Sulaver Borko Rajič Aida Pilav Copyright (c) 2019 Bosnian Journal of Basic Medical Sciences 2019-08-20 2019-08-20 19 3 210 212 10.17305/bjbms.2019.4266 Risk factors for complications and graft failure in kidney transplant patients with sepsis <p>Immunosuppressive therapies decrease the incidence of acute kidney rejection after kidney transplantation, but also increase the risk of infections and sepsis. This study aimed to identify the risk factors associated with complications and/or graft failure in kidney transplant patients with sepsis. A total of 14,658 kidney transplant patients with sepsis, identified in the National Inpatient Sample (NIS) database (data from 2005–2014), were included in the study and classified into three groups: patients without complications or graft failure/dialysis (Group 1), patients with complications only (Group 2), and patients with complications and graft failure/dialysis (Group 3). Multinomial logistic regression analyses were conducted to evaluate factors associated with kidney transplant recipients. Multivariate analysis showed that, compared to Group 1, patients from Group 2 or Group 3 were more likely to be Black and to have cytomegalovirus infection, coagulopathy, and glomerulonephritis (p ≤ 0.041). Also, Group 2 was more likely to have herpes simplex virus infection, and Group 3 was more likely to have hepatitis C infection and peripheral vascular disorders, compared to Group 1 (p ≤ 0.002). In addition, patients in Group 3 were more likely to be Black and to have hepatitis C infection, peripheral vascular disorders, coagulopathy, and hypertension compared to Group 2 (p ≤ 0.039). Age and female gender were associated with lower odds of complications after kidney transplantation regardless of graft rejection/dialysis (p ≤ 0.049). Hyperlipidemia and diabetes decreased the chance of complications and graft failure/dialysis after kidney transplant (p &lt; 0.001). In conclusion, the study highlights that black race, male gender, and specific comorbidities can increase the risk of complications and graft failure in kidney transplant patients with sepsis.</p> Syuan-Hao Syu Yung-Wei Lin Ke-Hsun Lin Liang-Ming Lee Chi-Hao Hsiao Yu-Ching Wen Copyright (c) 2018 Bosnian Journal of Basic Medical Sciences 2019-08-20 2019-08-20 19 3 304 311 10.17305/bjbms.2018.3874 Soft tissue grafts for dural reconstruction after meningioma surgery <p>The meninges are involved in various pathologies and are often directly or indirectly severed during surgical procedures, especially the dura mater. This can pose a real challenge for the surgeon, as a proper reconstruction of the meninges is important to prevent complications such as cerebrospinal fluid leak (CSF). A variety of techniques for dural reconstruction have been described, employing natural and artificial materials. A novel technique for dural reconstruction involves soft tissue grafts in the form of fibrous or fibromuscular flaps, which are placed on the dural defects to seal the gaps. These soft tissue grafts represent an appropriate scaffold for cell ingrowth and fibrosis, thus preventing CSF. In this pilot study, we described the application of soft tissue grafts for dural reconstruction in 10 patients who underwent convexity meningioma surgery.</p> Tomaz Velnar Lidija Gradisnik Copyright (c) 2019 Bosnian Journal of Basic Medical Sciences 2019-08-20 2019-08-20 19 3 297 303 10.17305/bjbms.2019.3949 Long noncoding RNA MALAT1 may be a prognostic biomarker in IDH1/2 wild-type primary glioblastomas <p>Primary glioblastoma (GB) is the most aggressive type of brain tumors. While mutations in isocitrate dehydrogenase (IDH) genes are frequent in secondary GBs and correlate with a better prognosis, most primary GBs are IDH wild-type. Recent studies have shown that the long noncoding RNA metastasis associated lung adenocarcinoma transcript-1 (MALAT1) is associated with aggressive tumor phenotypes in different cancers. Our aim was to clarify the prognostic significance of MALAT1 in <em>IDH1/2</em> wild-type primary GB tumors. We analyzed <em>IDH1/2</em> mutation status in 75 patients with primary GB by DNA sequencing. The expression of MALAT1 was detected in the 75 primary GB tissues and 5 normal brain tissues using reverse transcription quantitative PCR (RT-qPCR). The associations between MALAT1 expression, <em>IDH1/2</em> mutation status, and clinicopathological variables of patients were determined. <em>IDH1</em> (R132H) mutation was observed in 5/75 primary GBs. <em>IDH2</em> (R172H) mutation was not detected in any of our cases.&nbsp;MALAT1 expression was significantly upregulated in primary GB vs. normal brain tissues (<em>p</em> = 0.025). Increased MALAT1 expression in<em> IDH1/2</em> wild-type primary GBs correlated with patient age and tumor localization (<em>p </em>= 0.032 and <em>p</em> = 0.025, respectively). A multivariate analysis showed that high MALAT1 expression was an unfavorable prognostic factor for overall survival (<em>p = </em>0.034) in <em>IDH1/2 </em>wild-type primary GBs. High MALAT1 expression may have a prognostic role in primary GBs independent of IDH mutations.</p> Omer Gokay Argadal Melis Mutlu Secil Ak Aksoy Hasan Kocaeli Berrin Tunca Muhammet Nafi Civan Unal Egeli Gulsah Cecener Ahmet Bekar Mevlut Ozgur Taskapilioglu Cagla Tekin Gulcin Tezcan Sahsine Tolunay Copyright (c) 2019 Bosnian Journal of Basic Medical Sciences 2019-08-09 2019-08-09 19 3 10.17305/bjbms.2019.4297 Making sense of subclinical cardiac alterations in patients with diabetes <p>Patients with diabetes are prone to develop a distinct primary myocardial condition, diabetic cardiomyopathy, placing them at an increased risk for heart failure (1-3). This occurs independently of hypertension, coronary artery disease, and other established causes of heart failure. Pertinent findings include increased mass, concentric changes, and diastolic dysfunction of the left ventricle (4,5). Such adverse remodeling is common among patients with diabetes and appears to be strongly associated with its duration, suggesting a role for persistent metabolic stress (6-8). However, which exact components of the diabetic syndrome determine these cardiac alterations is not clear. Moreover, most studies have investigated patients with type 2 diabetes, and it is uncertain whether patients with type 1 diabetes experience similar myocardial changes.</p> <p><em>Continue reading full text in the <strong><a href="">preliminary PDF</a></strong> version.</em></p> Manan Pareek Michael Hecht Olsen Copyright (c) 2019 Bosnian Journal of Basic Medical Sciences 2019-08-01 2019-08-01 19 3 10.17305/bjbms.2019.4349 The potential of metabolic and lipid profiling in inflammatory bowel diseases: a pilot study <p>Inflammatory bowel diseases (IBDs) are conditions that still pose significant problems. A third of the patients are either misdiagnosed or a proper diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC) cannot be made. We need new biomarkers, so that we can offer patients the best treatment and keep the disease in an inactive state for as long as possible. Alterations in metabolic profiles have been incriminated in the pathophysiology of IBD. The aim of the present study was to identify molecules that could serve as biomarkers for a positive diagnosis of IBD as well as to discriminate UC from colonic CD. Twenty-two patients with active colonic IBD (UC = 17, CD = 5) and 24 age- and gender-matched healthy controls were enrolled. Plasma lipid and metabolic profiles were quantified using ultra-high performance liquid chromatography combined with mass spectrometry. Univariate and multivariate statistical tests were employed. Six lipid species and seven metabolites were significantly altered in IBD compared to healthy controls, with the majority belonging to glycerophospholipid, linoleic acid, and sphingolipid metabolisms. Five lipid species and only one metabolite were significantly increased in UC compared to CD. This preliminary study suggests that lipid and metabolic profiling of serum can become diagnostic tools for IBD. In addition, they can be used to differentiate between CD and UC.</p> Cristian Tefas Lidia Ciobanu Marcel Tanțău Corina Moraru Carmen Socaciu Copyright (c) 2019 Bosnian Journal of Basic Medical Sciences 2019-08-01 2019-08-01 19 3 10.17305/bjbms.2019.4235 A novel in ovo model to study cancer metastasis using chicken embryos and GFP expressing cancer cells <p>Cancer metastasis is the leading cause of cancer-related mortality worldwide. To date, several <em>in vitro</em> methodologies have been developed to understand the mechanisms of cancer metastasis and to screen various therapeutic agents against it. Nevertheless, mimicking an <em>in vivo</em> microenvironment <em>in vitro</em> is not possible; while <em>in vivo</em> experiments are complex, expensive and bound with several regulatory requirements. Herein, we report a novel <em>in ovo</em> model that relies on chicken embryo to investigate cancer cell invasion and metastasis to various organs of the body. In this model, we directly inject green fluorescent protein (GFP) expressing cancer cells to the heart of chicken embryo at 3 days of incubation, then monitor cell migration to various organs. To this end, we used a simple tissue processing technique to achieve rapid imaging and quantification of invasive cells. We were able to clearly observe the migration of GFP expressing cancer cells into various organs of chicken embryo. Organ specific variation in cell migration was also observed. Our new slide pressing based tissue processing technique improved the detectability of migrated cells. We herein demonstrate that the use of GFP expressing cancer cells allows easy detection and quantification of migrated cancer cells in the chicken embryo model, which minimizes the time and effort required in this types of studies compared to conventional histopathological analysis. In conclusion, our investigation provides a new cancer metastasis model that can be further improved to include more complex aspects, such as the use of multiple cell lines and anti-metastatic agents, thus opening new horizons in cancer biology and pharmaceutical research.</p> Robin Augustine Hashim Alhussain Anwarul Hasan Mohamed Badie Ahmed Huseyin C. Yalcin Ala-Eddin Al Moustafa Copyright (c) 2019 Bosnian Journal of Basic Medical Sciences 2019-07-24 2019-07-24 19 3 10.17305/bjbms.2019.4372 Effect of CCT137690 on long non-coding RNA expression profiles in MCF-7 and MDA-MB-231 cell lines <p>Long non-coding RNAs (lncRNAs) are involved in a range of biological processes, such as cellular differentiation, migration, apoptosis, invasion, proliferation, and transcriptional regulation. The aberrant expression of lncRNAs plays a significant role in several cancer types. Aurora kinases are increasingly expressed in various malignancies; accordingly, the inhibition of these enzymes may represent a novel approach for the treatment of various cancers. CCT137690, an Aurora kinase inhibitor, displays an anti-proliferative activity in human cancer cell lines. The aim of the present study was to investigate the anti-proliferative and cytotoxic effects of CCT137690 on estrogen receptor (ER)-positive human breast cancer cell line (MCF-7) and ER-negative human breast cancer cell line (MDA-MB-231). In addition, this study was targeted toward determining the changes induced in lncRNA expression levels following the initiation of Aurora kinase inhibitor treatment. The cytotoxic effects of CCT137690 were determined by means of the xCELLigence system. Furthermore, the anti-proliferative role of CCT137690 in breast cancer was investigated by checking the changes in lncRNA expression profiles using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The half-maximal inhibitory concentrations (IC50) of CCT137690 were determined as 4.5 μM (MCF-7) and 7.27 μM (MDA-MB-231). Several oncogenic lncRNAs (e.g., PRINS, HOXA1AS, and NCRMS) were downregulated in both ER-negative and ER-positive cell lines. On the other hand, tumor suppressor lncRNAs (e.g., DGCR5 and IGF2AS) were upregulated in the ER-positive cell line. After CCT137690 treatment, HOXA11AS and PCAT-14 lncRNAs were downregulated in the ER-positive cell lines. In addition, MER11C, SCA8, BC200, HOTAIR, PCAT-1, UCA1, SOX2OT, and HULC lncRNAs were downregulated in the ER-negative cell lines. The results of the present study indicated that Aurora kinase inhibitor CCT137690 could be a potential anti-cancer agent for breast cancer treatment.</p> Tuğçe Balcı Okcanoğlu Çağla Kayabaşı Cumhur Gündüz Copyright (c) 2019 Bosnian Journal of Basic Medical Sciences 2019-07-19 2019-07-19 19 3 10.17305/bjbms.2019.4155 Postoperative pulmonary complications in contemporary cohort of patients with pulmonary hypertension <p>Patients with pulmonary hypertension are at increased risk for postoperative pulmonary complications (PPCs). Herein, we review PPCs in pulmonary hypertension patients undergoing non-cardiac procedures under general anesthesia. The medical records of pulmonary hypertension patients who underwent surgery with general anesthesia between 2010 and 2017 were reviewed for PPCs. In addition we reviewed nursing-documented respiratory depressive episodes in the post-anesthesia care unit to assess the associations between these episodes and later PPCs. There were 20 PPCs among 128 patients who underwent 197 procedures (10.2 per 100 surgeries) [95% CI 6.7–15.2]. Of these, 5 occurred during anesthesia recovery and 15 following anesthesia recovery. Three-quarters of the PPCs occurred within 24 postoperative hours. All the PPCs were severe. The frequency of PPCs was significantly higher in those who experienced respiratory depression during anesthesia recovery vs. in those who did not (5/17, 29% vs. 10/175, 6%; odds ratio 5.15, 95% CI 1.58–16.81, <em>p</em> = 0.007). Increased PPC rates were observed among patients who were current/previous smokers and who routinely use benzodiazepines, and among those undergoing emergent surgery. With treatment, all PPCs resolved. The rate of PPCs in the population of contemporary surgical pulmonary hypertension patients was 10.2%, and three-quarters occurred during first 24 postoperative hours. Patients who had respiratory depression during anesthesia recovery were 5-fold more likely to experience later PPCs.</p> S. Chandralekha Kruthiventi Garvan C. Kane Juraj Sprung Toby N. Weingarten Mary Ellen Warner Copyright (c) 2019 Bosnian Journal of Basic Medical Sciences 2019-07-03 2019-07-03 19 3 10.17305/bjbms.2019.4332