Bosnian Journal of Basic Medical Sciences <p>The BJBMS (Bosnian Journal of Basic Medical Sciences) is а premier venue for discoveries in basic and clinical biomedical science. The BJBMS was founded in 1998 and is published by the Association of Basic Medical Sciences, a nonprofit honor organization of physician-scientists.</p> <p>Broad readership and scope. The BJBMS reaches readers across a wide range of medical disciplines and sectors. The journal publishes basic and translational/clinical research submissions and reviews in all biomedical specialties, including Genetics and Molecular biology, Immunology, Microbiology, Pathology, Biochemistry, Pharmacology, Anatomy, Biomaterials, new and emerging research and diagnostic methods, new and emerging medical entities, and others.</p> Association of Basic Medical Sciences of FBIH en-US Bosnian Journal of Basic Medical Sciences 1512-8601 Circ-RNF13, as an oncogene, regulates malignant progression of HBV-associated hepatocellular carcinoma cells and HBV expression and replication through circ-RNF13/miR-424-5p/TGIF2 ceRNA pathway <p><span data-preserver-spaces="true">The circular RNA RNF13 (circ-RNF13; ID: hsa_circ_0067717) is a novel identified abnormally upregulated circRNA in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) patients. However, its role and mechanism remain to be further annotated. The expression of circ-RNF13, microRNA (miR)-424-5p, and TGFβ-induced factor homeobox 2 (TGIF2) were detected by real-time quantitative PCR and western blotting, and their interaction was confirmed by dual-luciferase reporter assay. Functional assays were performed using MTS assay, colony formation assay, flow cytometry, enzyme-linked immunosorbent assay, transwell assay, and xenograft tumor model, along with real-time quantitative PCR. Circ-RNF13 was upregulated in HBV-infected human HCC tissues and HBV-expressing cells (Huh7-HBV and Hep3B-HBV), accompanied with TGIF2 upregulation and miR-424-5p downregulation. Blocking circ-RNF13 enhanced the apoptosis rate of Huh7-HBV and Hep3B-HBV cells but inhibited cell viability, colony formation, migration, and invasion, along with suppressed tumor growth&nbsp;</span><em><span data-preserver-spaces="true">in vivo</span></em><span data-preserver-spaces="true">. Besides, HBV DNA copies and levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were diminished by circ-RNF13 knockdown in Huh7-HBV and Hep3B-HBV cells. Mechanistically, circ-RNF13 and TGIF2 served as competing endogenous RNAs (ceRNAs) for miR-424-5p. Overexpressing miR-424-5p mimicked and silencing miR-424-5p counteracted the effects of circ-RNF13 depletion in HBV-expressing HCC cells</span><em><span data-preserver-spaces="true">&nbsp;in vitro</span></em><span data-preserver-spaces="true">. Consistently, TGIF2 restoration partially abrogated the role of miR-424-5p upregulation in Huh7-HBV and Hep3B-HBV cells. The circ-RNF13 sponged miR-424-5p to suppress HBV-associated HCC cells malignant progression and HBV infection by regulating TGIF2, providing a novel insight into the occurrence and treatment of HBV-associated HCC.&nbsp;</span></p> Yan Chen Shuhua Li Yinbin Wei Zhihong Xu Xiongfei Wu Copyright (c) 2021 Yan Chen, Shuhua Li, Yinbin Wei, Zhihong Xu, Xiongfei Wu 2021-02-18 2021-02-18 21 1 10.17305/bjbms.2020.5266 The impact of Ki-67 index, squamous differentiation and several clinicopathologic parameters on the recurrence of low and intermediate-risk endometrial cancer <p>Endometrial endometrioid carcinoma (EEC) represents approximately 75–80% of endometrial carcinoma cases. Three hundred thirty-six patients with EEC followed-up in the authors’ medical center between and 2010–2018 were included in our study. Two hundred seventy-two low- and intermediate- EEC patients were identified using the European Society for Medical Oncology criteria and confirmed by histopathological examination. Recurrence was reported in 17 of these patients. The study group consisted of patients with relapse. A control group of 51 patients was formed at a ratio of 3:1 according to age, stage, and grade, similar to that in the study group. Of the 17 patients with recurrent disease, 13 patients (76.5%) were stage 1A, and 4 patients (23.5%) were stage 1B. No significant difference was found in age, stage, and grade between the case and control groups (<em>p</em>&gt;0.05). Body mass index, parity, tumor size, lower uterine segment involvement, SqD, and Ki-67 index with <em>p</em>&lt;0.25 in the univariate logistic regression analysis were included in the multivariate analysis. Ki-67 was statistically significant in multivariate analysis (<em>p</em>=0.018); however, there was no statistical significance in SqD and other parameters. Our data suggest that the Ki-67 index rather than SqD needs to be assessed for recurrence in patients with low- and intermediate-risk EEC.</p> Birol Ocak Fatma Öz Atalay Ahmet Bilgehan Sahin Mine Ozsen Bahar Dakiki Seray Türe Merve Mesohorli Hikmet Utku Odman Özgür Tanrıverdi Gökhan Ocakoğlu Mehmet Bayrak Mehmet Bayrak Hakan Ozan Candan Demiröz Seda Sali Sibel Oyucu Orhan Adem Deligönül Erdem Cubukcu Türkkan Evrensel Copyright (c) 2021 Birol Ocak, Fatma Öz Atalay, Ahmet Bilgehan Sahin, Mine Ozsen, Bahar Dakiki, Seray Türe, Merve Mesohorli, Hikmet Utku Odman , Özgür Tanrıverdi, Gökhan Ocakoğlu, Mehmet Bayrak, Mehmet Bayrak, Hakan Ozan, Candan Demiröz, Seda Sali, Sibel Oyucu Orhan , Adem Deligönül, Erdem Cubukcu, Türkkan Evrensel 2021-02-18 2021-02-18 21 1 10.17305/bjbms.2020.5437 Clinicopathological characteristics and survival in lung signet ring cell carcinoma: a population-based study <p>Lung signet ring cell carcinoma (LSRCC) is a very rare type of lung cancer, the clinical characteristics, and prognosis of which remain to be clarified. In order to explore the clinicopathological and survival-related factors associated with LSRCC, we performed a large population-based cohort analysis of data included in the Surveillance, Epidemiology, and End Results (SEER) registry from 2001- 2015. A total of 752 LSRCC and 7518 lung mucinous adenocarcinoma (LMAC) patients were incorporated into our analysis, with respective mean ages of 63.8 and 67.5 years at the time of diagnosis. LSRCC patients were significantly more likely than LMAC patients to have distant-stage disease (72.1% vs. 45.8%, <em>p</em>&lt;0.0001), tumors of a high pathological grade (40.6% vs. 10.8%, <em>p</em>&lt;0.0001), have undergone chemotherapy (62.1% vs. 39.9%, p&lt;0.0001), be male (52.7% vs. 48.5%, <em>p</em>=0.03), and be &lt; 40 years old (3.3% vs. 1.3%, <em>p</em>=0.022), whereas they were less likely to have undergone surgical treatment (52.4% vs. 77.0%, <em>p</em>&lt;0.0001). LSRCC and LMAC patients exhibited median overall survival (OS) duration of 8 and 18 months (<em>p</em>&lt;0.0001), respectively, although these differences were not significant after adjusting for confounding variables. Independent factors associated with a favorable patient prognosis included a primary site in the middle or lower lung lobe, underwent surgery and underwent chemotherapy. However, age ≥ 80 years, higher grade, distant summary stage disease, and T4 stage disease were linked to poor prognosis. Patient age, tumor grade, primary tumor site, summary stage, T stage, surgery, and chemotherapy were all significantly associated with LSRCC patient prognosis.</p> Yunting Cai Yan Xie Yanli Xiong Wei Guan Yu Pu Dong Wang Mingfang Xu Shenglan Meng Copyright (c) 2021 Yunting Cai , Yan Xie , Yanli Xiong , Wei Guan , Yu Pu, Dong Wang, Mingfang Xu, Shenglan Meng 2021-02-15 2021-02-15 21 1 10.17305/bjbms.2020.5454 SARS-CoV-2 infection: Understanding the immune system abnormalities to get an adequate diagnosis <p>COVID-19 is the current pandemic caused by the novel coronavirus, SARS-CoV-2, that emerged from China at the end of December 2019. The scientific community is making extraordinary efforts to understand the virus structure and the pathophysiology and immunological processes activated in the host, in order to identify biomarkers, diagnostic tools, treatments, and vaccines to decrease COVID-19 incidence and mortality. Various abnormalities have been noted during SARS-CoV-2 infection both in lymphoid and myeloid cells. Such abnormalities may disturb the immune system function and cause a massive inflammatory response that impairs tissue function. This review discusses the close relationship between the immune system abnormalities and the broad spectrum of clinical manifestations, including fibrosis, in the context of COVID-19 disease. Moreover, we described the current strategies for COVID-19 diagnosis, and we provide a summary of the most useful clinical laboratory parameters to identify severe COVID-19 patients.</p> Karen Medina-Quero Omar Barreto-Rodriguez Voltaire Mendez-Rodriguez Anahí Sanchez-Moncivais Ivette Buendia-Roldan Leslie Chavez-Galan Copyright (c) 2021 Karen Medina-Quero, Omar Barreto-Rodriguez, Voltaire Mendez-Rodriguez, Anahí Sanchez-Moncivais, Ivette Buendia-Roldan, Leslie Chavez-Galan 2021-02-13 2021-02-13 21 1 10.17305/bjbms.2020.5400 Extreme lateral interbody fusion (XLIF) in a consecutive series of 72 patients <p>Extreme lateral interbody fusion (XLIF) has become the standard of minimally invasive lumbar segmental scoliosis treatment. Our objective is to determine the safety and efficacy of XLIF in spinal canal stenosis (SCS) and spondylodiscitis (SD). Patients treated with XLIF in our department between 2012 and 2018 were retrospectively analyzed. Patient records with clinical and radiographical parameters were evaluated. The patient cohort consists of 40 male and 32 female patients with a median age of 66.6 years. Forty-five patients had an SCS and 27 patients SD. The mean follow-up was 23 months. One level XLIF was performed in 49 patients, 2 levels in 15, 3 levels in 7 patients and 4 levels in 1 patient. All but one patient received an additional dorsal stabilization. The pain was present in all patients with a mean Visual Analogue Scale (VAS) score of 8.8 vs. postoperative VAS of 2.8 (<em>p</em>&lt;0.05). Preoperative neurological deficits were found in 44 patients. Only 6 patients had a neurological deterioration, 45 patients improved, and 21 patients remained unchanged. One patient experienced a perioperative complication.&nbsp; Non-fusion occurred in 8 cases. There were no outcome differences regarding pain and radiological outcome between patients with SCS and SD as well as between patients with one level vs. multilevel surgery. Baseline characteristics and the radiological outcome did not differ between the two groups. Patients with SD had a higher rate of worsening of neurological deficits following surgery, a higher rate of non-fusion, and a longer hospital stay. Patients with spinal canal stenosis SCS had a longer surgery time and more frequent adjacent segment disease.</p> Mirza Pojskic Benjamin Saβ Benjamin Völlger Christopher Nimsky Barbara Carl Copyright (c) 2021 Mirza Pojskic, Benjamin Saβ, Benjamin Völlger, Christopher Nimsky, Barbara Carl 2021-02-13 2021-02-13 21 1 10.17305/bjbms.2020.5261 Phylogenetic pattern of SARS-CoV-2 from COVID-19 patients from Bosnia and Herzegovina: lessons learned to optimize future molecular and epidemiological approaches <p>This is the first report of molecular and epidemiology findings from Bosnia and Herzegovina related to ongoing SARS-CoV-2 epidemic. Whole Genome Sequence of four samples from COVID-19 outbreaks was done in two laboratories in Bosnia and Herzegovina (Veterinary Faculty Sarajevo and Alea Genetic Center). All four BiH sequences cluster mainly with European ones (Italy, Austria, France, Sweden, Cyprus, England). The constructed phylogenetic tree indicates possible multiple independent introduction events.&nbsp; The data presented contributes to a better understanding of COVID-19 in the current reemergence of the disease.</p> Teufik Goletic Rijad Konjhodzic Nihad Fejzic Sejla Goletic Toni Eterovic Adis Softic Aida Kustura Lana Salihefendic Maja Ostojic Maja Travar Visnja Mrdjen Nijaz Tihic Sead Jazic Sanjin Musa Damir Marjanovic Mirsada Hukic Copyright (c) 2021 Teufik Goletic 2021-02-12 2021-02-12 21 1 10.17305/bjbms.2020.5381 Efficacy of chemotherapeutics in classic and non-classic Kaposi sarcoma: A single-center retrospective real-world data <p>Kaposi sarcoma is a rare disease and there is a gap in the literature about which chemotherapeutics should be applied, especially for the classical type. We aimed to present our institutional data on the demographic characteristics, treatment, and treatment efficacy in 16 Kaposi sarcoma (KS) patients treated with chemotherapy. We retrospectively analyzed the demographic and clinical characteristics, and the chemotherapeutic agents administered to the 16 KS patients diagnosed in our center and treated with chemotherapy, based on the medical records obtained. The median age, gender, type of KS, site of involvement, cytotoxic agents administered, progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety profiles of the patients were evaluated. The median age at disease onset was 61.07 years (range, 39.4–85.8 years). Among the patients, 1 had immunosuppression-related KS, 4 had AIDS-related KS, and 11 had classical KS. In the first-line cytotoxic therapy, 7 patients received pegylated-liposomal doxorubicin (PLD), 6 patients received paclitaxel, 2 patients received oral etoposide, and 1 patient received the adriamycin, bleomycin, and vincristine regimen. In the Kaplan–Meier analysis, the PFS was 39.9 months (95% CI, 7.7–72.0). In the first-line setting, a significant difference in terms of PFS was observed between the PLD- and paclitaxel-treated groups (not reached vs. 12.8 months, <em>p</em> = 0.033). The OS was 66.1 months (95% CI, 30.2–102.0). The ORR of the 16 patients was 43.8%, and their DCR was 81.3%. No grade 3 or 4 toxicity was observed. This retrospective study showed that PLD seems better than paclitaxel in terms of PFS and response rates and it has shown to have a good safety profile in KS patients.</p> Sibel Oyucu Orhan Ahmet Bilgehan Sahin Erdem Cubukcu Adem Deligonul Birol Ocak Bedrettin Orhan Turkkan Evrensel Copyright (c) 2021 Sibel Oyucu Orhan, Ahmet Bilgehan Sahin, Erdem Cubukcu, Adem Deligonul, Birol Ocak, Bedrettin Orhan, Turkkan Evrensel 2021-02-12 2021-02-12 21 1 10.17305/bjbms.2020.5329 Predictive performance of CT for adverse outcomes among COVID-19 suspected patients: a two-center retrospective study <p>The aim of the study was to compare the performance of various computed tomography (CT) reporting tools, including zonal CT visual score (ZCVS), the number of involved lobes, and Radiological Society of North America (RSNA) categorization in predicting adverse outcomes among patients hospitalized due to the lower respiratory symptoms during the coronavirus disease 2019 (COVID-19) pandemic. A total of 405 patients admitted with severe respiratory symptoms who underwent a chest CT were enrolled. The primary adverse outcome was intensive care unit (ICU) admission of patients. Predictive performances of reporting tools were compared using the area under the receiver operating characteristic curves (AUC ROC). Among the 405 patients, 39 (9.63%) required ICU support during their hospital stay. At least two or more observers reported a typical and indeterminate COVID-19 pneumonia CT pattern according to RSNA categorization in 70% (285/405) of patients. Among these, 63% (179/285) had a positive polymerase chain reaction (PCR test for the SARS-CoV-2 virus. The median number of lobes involved according to CT was higher in patients who required ICU support (median interquartile range [IQR], 5[3; 5] vs. 3[0; 5]). The median ZCVS score was higher among the patients that subsequently required ICU support (median [IQR], 4[0; 12] vs. 13[5.75; 24]). The bootstrap comparisons of AUC ROC showed significant differences between reporting tools, and the ZCVS was found to be superior (AUC ROC, 71-75%). The ZCVS score at the first admission showed a linear and significant association with adverse outcomes among patients with the lower respiratory tract symptoms during the COVID-19 pandemic.</p> Begümhan Baysal Mahmut Bilal Dogan Mutlu Gulbay Mine Sorkun Murathan Koksal Aliye Bastug Sumeyye Kazancioglu Bahadir Orkun Ozbay Sacit Icten Ferhat Arslan Yasemin Cag Hurrem Bodur Haluk Vahaboglu Copyright (c) 2021 Begümhan Baysal, Mahmut Bilal Dogan, Mutlu Gulbay, Mine Sorkun, Murathan Koksal, Aliye Bastug, Sumeyye Kazancioglu, Bahadir Orkun Ozbay, Sacit Icten, Ferhat Arslan, Yasemin Cag, Hurrem Bodur, Haluk Vahaboglu 2021-02-12 2021-02-12 21 1 10.17305/bjbms.2020.5466 Vancomycin-releasing cross-linked collagen sponges as wound dressings <p>The study presents a novel vancomycin-releasing collagen wound dressing derived from <em>Cyprinus carpio </em>collagen type I cross-linked with carbodiimide which retarded the degradation rate and increased the stability of the sponge. Following lyophilization, the dressings were subjected to gamma sterilization. The structure was evaluated via scanning electron microscopy images, micro-computed tomography, and infrared spectrometry. The structural stability and vancomycin release properties were evaluated in phosphate buffered saline. Microbiological testing and a rat model of a wound infected with methicillin-resistant <em>Staphylococcus aureus </em>(MRSA) were then employed to test the efficacy of the treatment of the infected wound. Following an initial mass loss due to the release of vancomycin, the sponges remained stable. After 7 days of exposure in phosphate buffered saline (37°C), 60% of the material remained with a preserved collagen secondary structure together with a high degree of open porosity (over 80%). The analysis of the release of vancomycin revealed homogeneous distribution of the antibiotic both across and between the sponges. The release of vancomycin was retarded as proved by <em>in vitro </em>testing and further confirmed by the animal model from which measurable concentrations were observed in blood samples 24 hours after the subcutaneous implantation of the sponge, which was more than observed following intraperitoneal administration. The sponge was also highly effective in terms of reducing the number of colony-forming units in biopsies extracted from the infected wounds 4 days following the inoculation of the wounds with the MRSA solution. The presented sponges have ideal properties to serve as wound dressing for prevention of surgical site infection or treatment of already infected wounds.</p> Jan Miroslav Hartinger Peter Lukáč Petr Mitáš Mikuláš Mlček Michaela Popková Tomáš Suchý Monika Šupová Jan Závora Václava Adámková Hana Benáková Ondřej Slanař Martin Šíma Martin Bartoš Hynek Chlup Tomáš Grus Copyright (c) 2019 BJBMS 2021-02-01 2021-02-01 21 1 61 70 10.17305/bjbms.2019.4496 MicroRNA-126 enhances the biological function of endothelial progenitor cells under oxidative stress via PI3K/Akt/GSK3β and ERK1/2 signaling pathways <p>Endothelial progenitor cell (EPC) transplantation is a safe and effective method to treat acute myocardial infarction (AMI). However, oxidative stress leads to the death of a large number of EPCs in the early stage of transplantation, severely weakening the therapeutic effect. Previous studies demonstrated that microRNAs regulate the biological function of EPCs. The aim of the current study was to investigate the effect of microRNA on the biological function of EPCs under oxidative stress. Quantitative reverse transcription PCR was performed to detect the expression of miR-126, miR-508-5p, miR-150, and miR-16 in EPCs from rats, among which miR-126 showed a relatively higher expression. Treatment with H<sub>2</sub>O<sub>2</sub> decreased miR-126 expression in EPCs in a dose-dependent manner. EPCs were further transfected with miR-126 mimics or inhibitors, followed by H<sub>2</sub>O<sub>2 </sub>treatment. Overexpression of miR-126 enhanced the proliferation, migration, and tube formation of H<sub>2</sub>O<sub>2</sub>-treated EPCs. MiR-126 overexpression also inhibited reactive oxygen species and malondialdehyde levels and enhanced superoxide dismutase levels, as well as increased angiopoietin (Ang)1 expression and decreased Ang2 expression in H<sub>2</sub>O<sub>2</sub>-treated EPCs. Moreover, miR-126 participated in the regulation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase 3β (GSK3β) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling in EPCs, where both pathways were activated after miR-126 overexpression in H<sub>2</sub>O<sub>2</sub>-treated EPCs. Overall, we showed that miR-126 promoted the biological function of EPCs under H<sub>2</sub>O<sub>2</sub>-induced oxidative stress by activating the PI3K/Akt/GSK3β and ERK1/2 signaling pathway, which may serve as a new therapeutic approach to treat AMI.</p> Qinqin Wu Benling Qi Xiaoyu Duan Xiaoyan Ming Fengqin Yan Yingxia He Xiaofen Bu Shan Sun Hong Zhu Copyright (c) 2020 Qinqin Wu, Benling Qi, Xiaoyu Duan, Xiaoyan Ming, Fengqin Yan, Yingxia He, Xiaofen Bu, Shan Sun, Hong Zhu 2021-02-01 2021-02-01 21 1 71 80 10.17305/bjbms.2019.4493 Knockdown of TPT1-AS1 inhibits cell proliferation, cell cycle G1/S transition, and epithelial–mesenchymal transition in gastric cancer <p>Long non-coding RNAs are considered to be critical regulators of tumor progression. Tumor protein translationally controlled 1 antisense RNA 1 (TPT1-AS1) was shown to have an oncogenic role in cervical and ovarian cancer. The clinical significance and biological function of TPT1-AS1 in gastric cancer (GC) are not clear. In this study, we analyzed the expression of TPT1-AS1 in GC tissues and cell lines and performed functional and mechanistic analysis of TPT1-AS1 effects on GC cell proliferation, migration, and invasion. TPT1-AS1 expression was determined in 76 pairs of GC tissues vs. matched adjacent normal tissues and in four GC cell lines (SGC-7901, AGS, BGC-823, and MGC-803) vs. GES-1 cell line by quantitative reverse transcription PCR. SGC-7901 and MGC-803 cells were transfected with small interfering RNA or scrambled negative control, and cell proliferation, colony formation, migration, invasion and cell cycle assays were performed. The expression of proteins involved in cell cycle progression and epithelial–mesenchymal transition was analyzed by Western blot. TPT1-AS1 expression was significantly higher in GC tissues and cell lines compared to controls. The overexpression of TPT1-AS1 was significantly correlated with TNM stage and lymph node metastasis, and it was associated with worse prognosis of GC patients according to the Kaplan–Meier survival analysis and Cox proportional hazard regression analysis. The knockdown of TPT1-AS1 significantly inhibited proliferation, cell cycle G1/S transition, migration, and invasion of SGC-7901 and MGC-803 cells. Moreover, TPT1-AS1 knockdown downregulated the expression of cyclin-dependent kinase (CDK) 4, cyclin D1, and vimentin and upregulated the expression of p21 and E-cadherin. Our findings suggest that TPT1-AS1 may be a promising therapeutic target in GC.</p> Jun Tang Fei Huang Hui Wang Feng Cheng Yaping Pi Juanjuan Zhao Zhihong Li Copyright (c) 2020 Jun Tang, Fei Huang, Hui Wang, Feng Cheng, Yaping Pi, Juanjuan Zhao, Zhihong Li 2021-02-01 2021-02-01 21 1 39 46 10.17305/bjbms.2020.4470 Asymptomatic neurotoxicity of amyloid β-peptides (Aβ1-42 and Aβ25-35) on mouse embryonic stem cell-derived neural cells <p>One of the strategies in the establishment of <em>in vitro</em> oxidative stress models for neurodegenerative diseases, such as Alzheimer’s disease (AD), is to induce neurotoxicity by amyloid beta (Aβ) peptides in suitable neural cells. Presently, data on the neurotoxicity of Aβ in neural cells differentiated from stem cells are limited. In this study, we attempted to induce oxidative stress in transgenic 46C mouse embryonic stem cell-derived neurons via treatment with Aβ peptides (Aβ<sub>1-42</sub> and Aβ<sub>25-35</sub>). 46C neural cells were generated by promoting the formation of multicellular aggregates, embryoid bodies in the absence of leukemia inhibitory factor, followed by the addition of all-trans retinoic acid as the neural inducer. Mature neuronal cells were exposed to different concentrations of Aβ<sub>1-42</sub> and Aβ<sub>25-35</sub> for 24 h. Morphological changes, cell viability, and intracellular reactive oxygen species (ROS) production were assessed. We found that 100 µM Aβ<sub>1-42</sub> and 50 µM Aβ<sub>25-35</sub> only promoted 40% and 10%, respectively, of cell injury and death in the 46C-derived neuronal cells. Interestingly, treatment with each of the Aβ peptides resulted in a significant increase of intracellular ROS activity, as compared to untreated neurons. These findings indicate the potential of using neurons derived from stem cells and Aβ peptides in generating oxidative stress for the establishment of an <em>in vitro </em>AD model that could be useful for drug screening and natural product studies.</p> Nur Izzati Mansor Carolindah Makena Ntimi Noraishah Mydin Abdul-Aziz King-Hwa Ling Aishah Adam Rozita Rosli Zurina Hassan Norshariza Nordin Copyright (c) 2020 Nur Izzati Mansor, Carolindah Makena Ntimi, Noraishah Mydin Abdul-Aziz, King-Hwa Ling, Aishah Adam, Rozita Rosli, Zurina Hassan, Norshariza Nordin 2021-02-01 2021-02-01 21 1 98 110 10.17305/bjbms.2020.4639 Association of miRNA-145 with the occurrence and prognosis of hydrosalpinx-induced defective endometrial receptivity <p>MiR-145 is reported to facilitate inflammation and is also associated with unsuccessful embryonic implantation. Whether miR-145 mediates inflammatory response underlying hydrosalpinx-induced defective endometrial receptivity (ER) remains unclear, and this study attempted to clarify this point. Endometrium samples were collected from hydrosalpinx patients (case, n = 243) and patients with tubal patency/obstruction (control, n = 187). The peripheral blood samples of cases and controls were collected to determine the genotypes of miR-145 SNPs. The value of miR-145 expression in the diagnosis and prognostic estimation of hydrosalpinx was assessed using ROC curve and regression analysis, respectively. Lipopolysaccharide (LPS) cell model was established with endometrial cells, and cells were transfected with miR-145 mimic, inhibitor, or negative control. MiR-145 and cytokine levels were quantified by quantitative reverse transcription PCR or western blot. MiR-145 expression was significantly higher in hydrosalpinx compared to control group, and high miR-145 expression was significantly associated with moderate/severe tube lesion, high pulsatility index (&gt;1.06), and high resistance index (&gt;0.61) in hydrosalpinx patients. ROC curve analysis indicated that monitoring miR-145 expression may be useful for the diagnosis of hydrosalpinx (AUC = 0.704). A alleles of rs41291957 (G&gt;A) and rs353292 (G&gt;A) were significantly associated with an increased risk of hydrosalpinx compared to G allele (<em>p </em>&lt; 0.05), yet the mutant allele of rs353291 (A&gt;G) and rs4705343 (T&gt;C) significantly reduced susceptibility to hydrosalpinx compared to the wild type allele. Treatments with miR-145 mimic and LPS in endometrial cells significantly increased the levels of transforming growth factor-β1, tumor necrosis factor -α, interleukin (IL)-6, and IL-8 compared to negative control, while treatment with miR-145 inhibitor decreased the cytokine levels. In conclusion, abnormally expressed miR-145 may be involved in hydrosalpinx-induced ER defects by regulating the inflammatory response.</p> Qingli Wang Haiquan Ai Xia Li Haiqing Tian Bingxue Ning Meng Zhang Xiaolin La Copyright (c) 2020 Qingli Wang, Haiquan Ai, Xia Li, Haiqing Tian, Bingxue Ning, Meng Zhang, Xiaolin La 2021-02-01 2021-02-01 21 1 81 92 10.17305/bjbms.2020.4538 Lessons learned from COVID-19 pandemic in Italy – A commentary <div>Since the COVID-19 outbreak, Italy has been one of the most affected countries in Europe and the second for number of deaths. In this commentary, we discuss some lessons that we learned as health-care providers working in a large public hospital during the pandemic, with a special focus on the importance of infection containment and early diagnosis, the role of swab, serological tests, home isolation and individual protection&nbsp; devices, and the available therapies and management indications to better face a possible new outbreak in the near future. These comments should stimulate a more diffused, efficient, and efficacious management of COVID-19 patients, also reducing the number of admissions to hospital emergency departments and the related spread of the infection.</div> Antonio Minni Massimo Ralli Francesca Candelori Fabrizio Cialente Lucia Ercoli Claudio Parlapiano Antonio Greco Marco de Vincentiis Copyright (c) 2020 Antonio Minni, Massimo Ralli, Francesca Candelori, Fabrizio Cialente, Lucia Ercoli, Claudio Parlapiano, Antonio Greco, Marco de Vincentiis 2021-02-01 2021-02-01 21 1 117 119 10.17305/bjbms.2020.4847 Targeting HER2 expression in cancer: New drugs and new indications <p>Functional activation of human epidermal growth factor receptor 2 (HER2) has been shown to strongly promote carcinogenesis, leading to the investigation of HER2-directed agents in cancers with HER2 genomic alterations. This has been best documented in the context of HER2 gene amplification in breast and gastric/gastroesophageal junction carcinomas for which several HER2-directed agents are available and have become a part of standard treatment regimens. Somatic HER2 gene mutations have been recently described at low frequency in a variety of human cancers and have emerged as a novel predictive biomarker for HER2-directed therapies. Preclinical data also indicate that activating HER2 mutations are potent oncogenic drivers in a manner that is analogous to HER2 amplification. HER2 mutations may clinically confer sensitivity to HER2-directed agents as recently shown in a phase II clinical trial with antibody-drug conjugate against HER2 trastuzumab deruxtecan in patients with non-squamous non-small cell lung carcinoma.</p> Semir Vranić Semir Bešlija Zoran Gatalica Copyright (c) 2020 Semir Vranic, Zoran Gatalica 2021-02-01 2021-02-01 21 1 1 4 10.17305/bjbms.2020.4908 Dose-dependent effects of adalimumab in neonatal rats with hypoxia/reoxygenation-induced intestinal damage <p>Tumor necrosis factor-alpha (TNF-α) has an important role in hypoxia/reoxygenation (H/R)-induced intestinal damage. It was shown that blocking TNF-α with infliximab has beneficial effects on experimental necrotizing enterocolitis and hypoxic intestinal injury. However, there is no data about the effect of adalimumab on H/R-induced intestinal damage. Therefore, we aimed to determine potential dose-dependent benefits of adalimumab in such damage in neonatal rats. Wistar albino rat pups were assigned to one of the four groups: control group, hypoxia group, low-dose adalimumab (5 mg/kg/day) treated group (LDAT), and high-dose adalimumab (50 mg/kg/day) treated group (HDAT). On the fourth day of the experiment, all rats except for the control group were exposed to H/R followed by euthanasia. Malondialdehyde (MDA), myeloperoxidase (MPO), TNF-α, total antioxidant capacity (TAC), and total oxidant capacity (TOC) were measured in intestinal tissue. TAC and TOC values were used to calculate the oxidative stress index (OSI). Histopathological injury scores (HIS) were also evaluated in the tissue samples. MDA levels were significantly lower in the LDAT and HDAT groups (<em>p</em> &lt; 0.001). TNF-α levels were significantly lower in the LDAT group (<em>p</em> &lt; 0.001). OSI was significantly higher in the H/R group than in the control and LDAT groups (<em>p</em> &lt; 0.001). Mean HIS values in the LDAT group were significantly lower than those in the H/R and HDAT groups (<em>p</em> &lt; 0.001). This experimental study showed that low-dose adalimumab appears to have a beneficial effect on intestinal injury induced with H/R in neonatal rats.</p> Halil Kocamaz Özmert MA Özdemir Nilay Şen Türk Yaşar Enli Barbaros Şahin Hacer Ergin Copyright (c) 2020 Halil Kocamaz, Özmert MA Özdemir, Nilay Şen Türk, Yaşar Enli, Barbaros Şahin, Hacer Ergin 2021-02-01 2021-02-01 21 1 33 38 10.17305/bjbms.2020.4823 The role of glycogen synthase kinase 3 (GSK3) in cancer with emphasis on ovarian cancer development and progression: A comprehensive review <p>Glycogen synthase kinase 3 (GSK3) is a monomeric serine-threonine kinase discovered in 1980 in a rat skeletal muscle. It has been involved in various cellular processes including embryogenesis, immune response, inflammation, apoptosis, autophagy, wound healing, neurodegeneration, and carcinogenesis. GSK3 exists in two different isoforms, GSK3α and GSK3β, both containing seven antiparallel beta-plates, a short linking part and an alpha helix, but coded by different genes and variously expressed in human tissues. In the current review, we comprehensively appraise the current literature on the role of GSK3 in various cancers with emphasis on ovarian carcinoma. Our findings indicate that the role of GSK3 in ovarian cancer development cannot be decisively determined as the currently available data support both prooncogenic and tumor-suppressive effects. Likewise, the clinical impact of GSK3 expression on ovarian cancer patients and its potential therapeutic implications are also limited. Further studies are needed to fully elucidate the pathophysiological and clinical implications of GSK3 activity in ovarian cancer.</p> Mislav Glibo Alan Serman Valentina Karin-Kujundzic Ivanka Bekavac Vlatkovic Berivoj Miskovic Semir Vranic Ljiljana Serman Copyright (c) 2020 Mislav Glibo, Alan Serman, Valentina Karin-Kujundzic, Ivanka Bekavac Vlatkovic, Berivoj Miskovic, Semir Vranic, Ljiljana Serman 2021-02-01 2021-02-01 21 1 5 18 10.17305/bjbms.2020.5036 Cross-sectional imaging and cytologic investigations in the preoperative diagnosis of parotid gland tumors – An updated literature review <p>An accurate preoperative diagnosis of parotid tumors is essential for the selection and planning of surgical treatment. Various modern cross-sectional imaging and cytologic investigations can support the differential diagnosis of parotid tumors. The aim of this study was to achieve a comprehensive and updated review of modern imaging and cytologic investigations used in parotid tumor diagnosis, based on the latest literature data. This literature review could serve as a guide for clinicians in selecting different types of investigations for the preoperative differential diagnosis of parotid tumors. Magnetic resonance imaging (MRI) with its dynamic and advanced sequences is the first-line imaging investigation used in differentiating parotid tumors. Computed tomography (CT) and positron emission tomography (PET)-CT provide limited indications in differentiating parotid tumors. Fine needle aspiration biopsy and core needle biopsy can contribute with satisfactory results to the cytological diagnosis of parotid tumors. Dynamic MRI with its dynamic contrast-enhanced and diffusion-weighted sequences provides the best accuracy for the preoperative differential diagnosis of parotid tumors. CT allows the best evaluation of bone invasion, being useful when MRI cannot be performed, and PET-CT has value in the follow-up of cancer patients. The dual cytological and imaging approach is the safest method for an accurate differential diagnosis of parotid tumors.</p> Sebastian Stoia Grigore Băciuț Manuela Lenghel Radu Badea Csaba Csutak Georgeta Mihaela Rusu Mihaela Băciuț Tiberiu Tamaș Emil Boțan Gabriel Armencea Simion Bran Cristian Dinu Copyright (c) 2020 Sebastian Stoia, Grigore Băciuț, Manuela Lenghel , Radu Badea , Csaba Csutak , Georgeta Mihaela Rusu , Mihaela Băciuț, Tiberiu Tamaș, Emil Boțan , Gabriel Armencea , Simion Bran , Cristian Dinu 2021-02-01 2021-02-01 21 1 19 32 10.17305/bjbms.2020.5028 SARS-CoV-2 virus outbreak and the emergency public health measures in Bosnia and Herzegovina: January – July, 2020 <p>Between March 5<sup>th</sup> and July 25<sup>th</sup>, 2020, the total number of SARS-CoV-2 confirmed cases in Bosnia and Herzegovina (BH) was 10,090, corresponding to a cumulative incidence rate of 285.7/100,000 population. Demographic and clinical information on all the cases along with exposure and contact information were collected using a standardized case report form. In suspected SARS-CoV-2 cases, respiratory specimens were collected and tested by real-time reverse-transcriptase polymerase chain reaction assay. The dynamic of the outbreak was summarized using epidemiological curves, instantaneous reproduction number R<sub>t</sub>, and interactive choropleth maps for geographical distribution and spread. The rate of hospitalization was 14.0%(790/5646) in the Federation of Bosnia and Herzegovina (FBH) and 6.2% (267/4299) in the Republic of Srpska (RS). The death rate was 2.2% (122/5646) in FBH and 3.6% in the RS (155/4299). After the authorities lifted mandatory quarantine restrictions, the instantaneous reproduction number increased from 1.13 on May 20<sup>th</sup> to 1.72 on May 31<sup>st</sup>. The outbreak concerns both entities, FBH and RS, and it is more pronounced in those aged 20-44 years. It is important to develop the communication and emergency plan for the SARS-CoV-2 outbreak in BH, including the mechanisms to allow the ongoing notification and updates at the national level.</p> Mirsada Hukic Mirza Ponjavic Emin Tahirovic Almir Karabegovic Elvir Ferhatbegovic Maja Travar Fadila Serdarevic Copyright (c) 2020 Mirsada Hukic, Mirza Ponjavic, Emin Tahirovic, Almir Karabegovic, Elvir Ferhatbegovic, Maja Travar, Fadila Serdarevic 2021-02-01 2021-02-01 21 1 111 116 10.17305/bjbms.2020.5081 Rapid, multimodal, critical care knowledge-sharing platform for COVID-19 pandemics <p>In many areas of the world, critical care providers caring for COVID-19 patients lacked specific knowledge and were exposed to the abundance of new and unfiltered information. With support from the World Health Organization, we created a multimodal tele-education intervention to rapidly share critical care knowledge related to COVID-19 targeting providers in a region of Southeastern Europe. We delivered 60-minute weekly interactive tele-education sessions over YouTube<sup>TM</sup> between March 2020 and May 2020, supplemented by a dedicated webpage. The intervention was reinforced using a secure social media platform (Viber<sup>TM</sup>), providing continuous rapid knowledge exchange among faculty and learners. A high level of engagement was observed, with over 2000 clinicians participating and actively interacting over a 6-week period. Surveyed participants were highly satisfied with the intervention. Tele-education interventions using social media platforms are feasible, low-cost, and effective methods to share knowledge during the COVID-19 pandemic.</p> Amra Sakusic Dragana Markotic Yue Dong Emir Festic Vladimir Krajinovic Zoran Todorovic Alan Sustic Natasa Milivojevic Milka Jandric Srdjan Gavrilovic Alexander Niven Pedja Kovacevic Ognjen Gajic Copyright (c) 2020 Amra Sakusic, Dragana Markotic, Yue Dong, Emir Festic, Vladimir Krajinovic, Alan Sustic, Natasa Milivojevic, Milka Jandric, Srdjan Gavrilovic, Alexander Niven, Pedja Kovacevic, Ognjen Gajic 2021-02-01 2021-02-01 21 1 93 97 10.17305/bjbms.2020.4934