Bosnian Journal of Basic Medical Sciences 2020-07-29T12:06:07+02:00 Faruk Skenderi Open Journal Systems <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> Concordance of PD-L1 expression and CD8+ TIL intensity between NSCLC and synchronous brain metastases 2020-06-28T00:42:10+02:00 Sebnem Batur Onur Dulger Sermin Durak Perran Fulden Yumuk Hale Basak Caglar Emine Bozkurtlar Suheyla Bozkurt Ebru Tastekin Irfan Cicin Rengin Ahiskali Rashad Rzazade Asli Cakir Buge Oz <p>Programmed death-ligand 1 (PD-L1) is suggested to be a predictive biomarker in non-small-cell lung carcinoma (NSCLC). However, the differential expression of PD-L1 in primary lung tumor vs. synchronous metastases, especially brain metastasis (BM), remains unclear. This study assessed the concordance of PD-L1 expression on tumor cells and tumor-infiltrating lymphocytes (TILs) and CD8<sup>+</sup> TIL intensity between primary lung tumors and synchronous BMs from 24 NSCLC patients. PD-L1, CD3, and CD8 positivity was determined by immunohistochemistry (IHC). PD-L1 scoring was based on the proportion of tumor cells with membranous expression of PD-L1 and the cutoff values &lt;1%, 1–49%, and ≥50%. CD3 and CD8 positivity in TILs was evaluated semi-quantitatively and the proportion of CD3<sup>+</sup>/CD8<sup>+</sup> TILs was determined. PD-L1 expression on tumor cells and TILs was evaluated in relation to CD3<sup>+</sup>/CD8<sup>+</sup> TIL proportions and the intensity of CD8<sup>+</sup> TILs between the paired primary lung and BM tissues. In the primary lung tumors, PD-L1 positivity was observed in 25%, 37.5%, and 37.5% cases for the cutoff values &lt;1%, 1–49%, and ≥50%, respectively. PD-L1 expression on tumor cells was strongly correlated between the paired primary lung and BM tissues, in all cutoff groups. However, PD-L1 expression on TILs and the proportion of CD3<sup>+</sup>/CD8<sup>+</sup> TILs were not strongly correlated in all three groups between the paired primary lung tumors and BMs. The intensity of CD8<sup>+</sup> TILs was concordant in only 54.16% of the paired primary lung tumors and BMs. This study showed a high concordance of PD-L1 expression in neoplastic cells between primary NSCLC and synchronous BMs.</p> 2020-08-03T00:00:00+02:00 Copyright (c) 2020 Sebnem Batur, Onur Dulger, Buge Oz Significance of chromogranin A and synaptophysin in pancreatic neuroendocrine tumors 2020-06-28T00:42:10+02:00 Tatsuo Tomita <p>The two most commonly used immunohistochemical markers for neuroendocrine cells and their tumors are chromogranin A (CgA) and synaptophysin (SPY). CgA is a marker for neuroendocrine secretory granules of four pancreatic hormones and gastrin while SPY is a marker for synaptic vesicles in neuroendocrine cells, which release classic neurotransmitters such as acetylcholine and others. CgA is involved in synthesis and secretion of peptide hormones through exocytosis while the function of SPY is elusive. Thirty-five pancreatic neuroendocrine tumors (Pan-NETs) were studied, consisting of 14 insulinomas, 8 gastrinomas, 2 glucagonomas, 6 pancreatic polypeptidomas and 5 non-functioning tumors, and were immunostained for four pancreatic hormones, gastrin, CgA, and SPY. Majority of Pan-NETs were less immunostained for the endocrine hormones and CgA than the normal pancreatic endocrine cells. CgA immunostaining mostly correlates with each hormone staining in non-β-cell tumors, while SPY immunostaining recognizes endocrine cells diffusely in the cytoplasm. CgA immunostaining is less in insulinomas than in non-β-cell tumors, and CgA immunostaining may distinguish CgA-weaker insulinomas from CgA-stronger non-β-cell tumors. CgA immunostaining may be used as an independent marker for biological aggressiveness in non-β-cell Pan-NETs. The serum CgA levels are higher in subjects harboring non-β-cell tumors than those harboring insulinomas, and the serum CgA elevates in parallel to the increasing metastatic tumor mass. Thus, CgA positive immunostaining in Pan-NETs correlates with the elevated serum levels of CgA for diagnosing CgA-positive non-β-cell Pan-NETs and the increasing serum CgA levels indicate increasing metastatic tumor mass.</p> 2020-08-03T00:00:00+02:00 Copyright (c) 2020 Tatsuo Tomita Neurological outcome in patients after successful resuscitation in out-of-hospital settings 2020-06-28T00:42:11+02:00 Martin Marinšek Andreja Sinkovič David Šuran <p>Neurological outcome is an important determinant of death in admitted survivors after out-of-hospital cardiac arrest (OHCA). Studies demonstrated several significant pre-hospital predictors of ischemic brain injury (time to resuscitation, time of resuscitation, and cause of OHCA). Our aim was to evaluate the relationship between post-resuscitation clinical parameters and neurological outcome in OHCA patients, when all recommended therapeutic strategies, including hypothermia, were on board. We retrospectively included consecutive 110 patients, admitted to the medical ICU after successful resuscitation due to OHCA. Neurological outcome was defined by cerebral performance category (CPC) scale I-V. CPC categories I-II defined good neurological outcome and CPC categories III-V severe ischemic brain injury. Therapeutic measures were aimed to achieve optimal circulation and oxygenation, early percutaneous coronary interventions (PCI) in acute coronary syndromes (ACS), and therapeutic hypothermia to improve survival and neurological outcome of OHCA patients. We observed good neurological outcome in 37.2% and severe ischemic brain injury in 62.7% of patients. Severe ischemic brain injury was associated significantly with known pre-hospital data (older age, cause of OHCA, and longer resuscitations), but also with increased admission lactate, in-hospital complications (involuntary muscular contractions/seizures, heart failure, cardiogenic shock, acute kidney injury, and mortality), and inotropic and vasopressor support. Good neurological outcome was associated with early PCI, dual antiplatelet therapy, and better survival. We conclude that in OHCA patients, post-resuscitation early PCI and dual antiplatelet therapy in ACS were significantly associated with good neurological outcome, but severe ischemic brain injury was associated with several in-hospital complications and the need for vasopressor and inotropic support.</p> 2020-08-03T00:00:00+02:00 Copyright (c) 2020 Martin Marinšek, Andreja Sinkovič, David Šuran Post-operative functional neurological symptom disorder after anesthesia 2020-06-28T00:42:11+02:00 Ryan S. D’Souza Matthew N.P. Vogt Edwin H. Rho <p>A rare manifestation during the post-anesthetic period may include the occurrence of functional neurological symptom disorder (FNSD). FNSD is described as neurological symptoms that are not consistently explained by neurological or medical conditions. We report a case series consisting of six patients who underwent a general anesthetic at a tertiary referral hospital and experienced FNSD in the immediate post-anesthetic period. Life-threatening causes were excluded based on benign physical exam findings and knowledge of past history. Five of six cases manifested with FNSD only in the immediate post-operative setting after exposure to anesthesia, and never otherwise experienced these symptoms during their normal daily lives. MEDLINE and Google Scholar were searched through October 2019 using a highly-sensitive search strategy and identified 38 published cases of post-anesthetic FNSD. Meta-analysis of pooled clinical data revealed that a significant proportion of patients were females (86%), reported a history of psychiatric illness (49%), reported a prior history of FNSD (53%), and underwent general anesthesia as the primary anesthetic (93%). The majority of patients were exposed to diagnostic studies (66% received radiographic tests and 52% received electroencephalogram) as well as pharmacologic therapy (57%). While no deaths occurred, many patients had unanticipated admission to the hospital (53%) or to the intensive care unit (25%). These data may help inform the anesthesia literature on presentation, risk factors, and treatment outcomes of FNSD in the context of anesthetic administration. We contemplate whether anesthetic agents may predispose a vulnerable brain to manifest with involuntary motor and sensory control seen in FNSD.</p> 2020-08-03T00:00:00+02:00 Copyright (c) 2020 Ryan S D'Souza, Matthew NP Vogt, Edwin Rho Inhibitory effect of microRNA-608 on lung cancer cell proliferation, migration, and invasion by targeting BRD4 through the JAK2/STAT3 pathway 2020-06-28T00:42:10+02:00 Weigang Xu Dapeng Sun Yanqin Wang Xinlin Zheng Yan Li Yu Xia Ya'nan Teng <p>Lung cancer is the leading cause of cancer-related mortality around the world. This malignancy has a 5-year survival rate of 21%, because most of the patients are diagnosed in the middle or late stage of the disease when local metastasis and tumor invasion have already progressed. Therefore, the investigation of the pathogenesis of lung cancer is an issue of crucial importance. MicroRNAs (miRNAs) seem to be involved in the evolution and development of lung cancer. MicroRNA-608 is likely to be downregulated in lung cancer tissues. Regarding this, the current study involved the determination of the fundamental mechanism of microRNA-608 in the development of lung cancer. Based on the results of quantitative&nbsp;reverse transcription&nbsp;polymerase chain reaction (RT-qPCR), the expression level of microRNA-608 was downregulated in 40 lung cancer tissues, compared to that in the adjacent normal tissues. The results of dual-luciferase reporter assay revealed that bromodomain-containing protein 4 (<em>BRD4</em>) was the direct target of microRNA-608. Accordingly, the lung cancer tissues had an elevated expression level of <em>BRD4,</em> in contrast to the adjacent normal tissues. The results of Cell Counting Kit 8 assay demonstrated that the high expression of microRNA-608 notably restrained lung cancer cell proliferation. The scratch wound and transwell assays showed that the upregulation of microRNA-608 suppressed the migration and invasion of lung cancer cells. Finally, the western blot assay showed that in the microRNA-608 mimics group, the expression levels of BRD4, p-JAK2, p-STATA3, CD44, and MMP9 were significantly decreased, compared with those in the negative control miRNA mimics group. Our results indicate that high expression of microRNA-608 inhibits the proliferation, migration, and invasion of lung cancer cells by targeting <em>BRD4</em> via the JAK2/STAT3 pathway.</p> 2020-08-03T00:00:00+02:00 Copyright (c) 2020 Authors MALAT1 inhibits the Wnt/β-catenin signaling pathway in colon cancer cells and affects cell proliferation and apoptosis 2020-06-28T00:42:11+02:00 Junjun Zhang Qian Li Bing Xue Rui He <p>Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) is a highly conserved long noncoding RNA, which has been related to various pathological processes, including cancer. The role and mechanism of MALAT1 in colon cancer are not clear. We investigated MALAT1 expression in colon cancer tissues, the effect of MALAT1 on proliferation and apoptosis of SW480 cells, and the signaling pathway involved in the MALAT1 effects. MALAT1 expression was determined in 60 colon cancer and para-carcinoma tissues using reverse transcription polymerase chain reaction (RT-PCR). Knockdown of MALAT1 in SW480 cells was induced by small interfering RNA (siRNA), and the cells were divided into three groups: untreated control, nonsense siRNA-treated control, and MALAT1 siRNA-treated group. SW480 cell apoptosis was assessed using TUNEL assay and flow cytometry. Apoptosis-related and Wnt/β-catenin signaling pathway-related proteins were detected by Western blotting in SW480 cells. SW480 cell proliferation was assessed by CCK-8 assay. MALAT1 expression was significantly higher in colon cancer vs. para-carcinoma tissues. Knockdown of MALAT1 by siRNA increased the number of apoptotic cells and the apoptosis rate at 24 h post-transfection in SW480 cells. Bcl2 associated X protein (Bax) expression was increased, B-cell lymphoma 2 (Bcl-2) expression was decreased, and the ratio of cleaved caspase-3 to truncated caspase-3 was increased in MALAT1 siRNA-transfected SW480 cells. MALAT1 knockdown decreased the proliferation of SW480 cells at 24 h, 48 h, and 72 h post-transfection. Wnt and β-catenin expression was inhibited in MALAT1 siRNA-transfected SW480 cells. Inhibition of MALAT1 expression in colon cancer may promote apoptosis and hinder cell proliferation by suppressing the activation of Wnt/β-catenin signaling pathway.</p> 2020-08-03T00:00:00+02:00 Copyright (c) 2019 Authors Circulating long noncoding RNAs H19 and GAS5 are associated with type 2 diabetes but not with diabetic retinopathy: A preliminary study 2020-06-28T00:42:11+02:00 Manal S. Fawzy Ahmed A. Abdelghany Eman A. Toraih Abeer M. Mohamed <p>Recently, a wide range of biological and pathological roles of long noncoding RNAs (lncRNAs) have been discovered. However, the potential role of circulating lncRNAs H19 and GAS5 in type 2 diabetes mellitus (T2DM) and diabetic retinopathy (DR) is not clear. Here, we assessed the plasma levels of H19 and GAS5 lncRNAs in T2DM patients with/without DR and evaluated if H19 and GAS5 pre-treatment plasma levels are a predictor of early response to a single aflibercept dose in DR subgroup. Plasma lncRNA expression profiles of 119 T2DM patients (66 with DR and 53 without DR) and 110 healthy controls were determined by quantitative reverse transcription PCR. The association of lncRNA expression profiles with clinical features and aflibercept early response in DR patients was investigated. Relative H19 expression levels were significantly increased in T2DM group (including DR and non-DR subgroups) vs. controls, while GAS5 levels were decreased in T2DM group (<em>p </em>&lt; 0.001). There was no significant difference in H19 and GAS5 expression levels between DR and non-DR subgroups. H19 and GAS5 expression profiles were not significantly correlated with clinical parameters or response to aflibercept therapy in DR subgroup. Our findings indicate that the circulating lncRNAs H19 and GAS5 may be associated with T2DM prevalence but may not have an important diagnostic/prognostic role in DR or early response to aflibercept intravitreal injection in DR patients. Large-scale transcriptomic studies are warranted to validate our results and investigate other lncRNA candidates in T2DM.</p> 2020-08-03T00:00:00+02:00 Copyright (c) 2020 Manal S. Fawzy, Ahmed A. Abdelghany , Eman A. Toraih Galectin-1 reduces the severity of dextran sulfate sodium (DSS)-induced ulcerative colitis by suppressing inflammatory and oxidative stress response 2020-06-28T00:42:10+02:00 Pelin Arda-Pirincci Guliz Aykol-Celik <p>Ulcerative colitis is an inflammatory bowel disease that affects a large number of people around the world. Galectin-1 is a β-galactoside-binding lectin with a broad range of biological activities. The effects of galectin-1 on dextran sulfate sodium (DSS)-induced ulcerative colitis <em>in vivo</em> is not clear. We investigated the effect of galectin-1 on colon morphology, cell proliferation, oxidative stress, antioxidant system, and proinflammatory/antiinflammatory cytokines in a DSS-induced mouse model of ulcerative colitis. Thirty-two C57BL/6 mice were randomly assigned to one of the four groups: control, acute colitis, galectin-1, and DSS+galectin-1. Controls were treated with phosphate-buffered saline (PBS) for seven days. Acute colitis was induced by 3% DSS in drinking water administered orally for five days. Mice in galectin-1 groups were treated with 1 mg/kg recombinant human galectin-1 in PBS for seven consecutive days. Oral DSS administration resulted in acute colitis by causing histopathological changes; an increase in disease activity index (DAI), lipid peroxidation (malondialdehyde [MDA]), myeloperoxidase (MPO), and tumor necrosis factor (TNF)-α levels; a decrease in body weight, colon length, cell proliferation index, catalase, glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities, and GSH and interleukin (IL)-10 levels. The treatment with galectin-1 attenuated DSS-induced acute colitis by reducing DAI, MDA, MPO, and TNF-α levels and by increasing body weight, colon length, cell proliferation, antioxidant enzyme activity, GSH, and IL-10 levels. These findings suggest that galectin-1 has proliferative, antioxidant, antiinflammatory, and cytoprotective effects against DSS-induced ulcerative colitis in mice. Due to its antiinflammatory and antioxidant activity galectin-1 may be effective in preventing and treating ulcerative colitis.</p> 2020-08-03T00:00:00+02:00 Copyright (c) 2020 Pelin Arda-Pirincci, Guliz Aykol-Celik Androgen effect on connexin expression in the mammalian female reproductive system: A systematic review 2020-06-28T00:42:10+02:00 Datu Agasi Mohd Kamal Siti Fatimah Ibrahim Mohd Helmy Mokhtar <p>The functions of androgen and connexin in the mammalian female reproductive system are suggested to be related. Previous research has shown that androgen affects connexin expression in the female reproductive system, altering its function. However, no definitive conclusion on their cause-effect relationship has been drawn yet. In addition, a high prevalence of women with polycystic ovary syndrome (PCOS), who are characterized by elevated androgen levels and failure of ovulation, has prompted the studies on the relationship between androgen and connexin in the ovaries. This systematic review aims to investigate the effect of androgen on connexin expression in the mammalian female reproductive system. The literature search was conducted using the MEDLINE via EBSCOhost and the Scopus database and the following keywords: “androgen” or “testosterone” or “androgen blocker” or “anti-androgen” or “androstenedione” or “dehydroepiandrosterone” or “flut­amide AND connexin” or “gap junction” or “cell junction”. We only considered <em>in vitro </em>and <em>in vivo </em>studies that involved treatment by androgen or androgen receptor blockers and measured connexin expression as one of the parameters. Our review showed that the exposure to androgen or androgen blocker affects connexin expression but not its localization in the mammalian ovary. However, it is not clear whether androgen downregulates or upregulates connexin expression.</p> 2020-08-03T00:00:00+02:00 Copyright (c) 2020 Authors The natural adaptive evolution of cancer: The metastatic ability of cancer cells 2020-06-28T00:42:10+02:00 Gheorghe-Emilian Olteanu Ioana-Maria Mihai Florina Bojin Oana Gavriliuc Virgil Paunescu <p>The ability of cancer to adapt renders it one of the most challenging pathologies of all time. It is the most dreaded pathological entity because of its capacity to metastasize to distant sites in the body, and 90% of all cancer-related deaths recorded to date are attributed to metastasis. Currently, three main theories have been proposed to explain the metastatic pathway of cancer: the epithelial–mesenchymal transition (EMT) and mesenchymal–epithelial transition (MET) hypothesis (1), the cancer stem cell hypothesis (2), and the macrophage–cancer cell fusion hybrid hypothesis (3). We propose a new hypothesis, i.e., under the effect of particular biochemical and/or physical stressors, cancer cells can undergo nuclear expulsion with subsequent macrophage engulfment and fusion, with the formation of cancer fusion cells (CFCs). The existence of CFCs, if confirmed, would represent a novel metastatic pathway and a shift in the extant dogma of cancer; consequently, new treatment targets would be available for this adaptive pathology.</p> 2020-08-03T00:00:00+02:00 Copyright (c) 2020 Gheorghe-Emilian Olteanu, Ioana-Maria Mihai, Florina Bojin, Oana Gavriliuc, Virgil Paunescu A key bacterial cytoskeletal cell division protein FtsZ as a novel therapeutic antibacterial drug target 2020-06-28T00:42:10+02:00 Mujeeb ur Rahman Ping Wang Na Wang Yaodong Chen <p>Nowadays, the emergence of multidrug-resistant bacterial strains initiates the urgent need for the elucidation of the new drug targets for the discovery of antimicrobial drugs. Filamenting temperature-sensitive mutant Z (FtsZ), a eukaryotic tubulin homolog, is a GTP-dependent prokaryotic cytoskeletal protein and is conserved among most bacterial strains. <em>I</em><em>n vitro </em>studies revealed that FtsZ self-assembles into dynamic protofilaments or bundles and forms a dynamic Z-ring at the center of the cell <em>in vivo</em>, leading to septation and consequent cell division. Speculations on the ability of FtsZ in the blockage of cell division make FtsZ a highly attractive target for developing novel antibiotics. Researchers have been working on synthetic molecules and natural products as inhibitors of FtsZ. Accumulating data suggest that FtsZ may provide the platform for the development of novel antibiotics. In this review, we summarize recent advances in the properties of FtsZ protein and bacterial cell division, as well as in the development of FtsZ inhibitors.</p> 2020-08-03T00:00:00+02:00 Copyright (c) 2020 Mujeeb Rahman, Ping Wang, Na Wang, Yaodong Chen SARS-CoV-2 infection of the nervous system: A review of the literature on neurological involvement in novel coronavirus disease-(COVID-19) 2020-06-28T00:42:10+02:00 Alvin Oliver Payus Constance Liew Sat Lin Malehah Mohd Noh Mohammad Saffree Jeffree Raymond Azman Ali <p>The novel coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is believed to have emerged from an animal source and has been spreading rapidly among humans. Recent evidence shows that SARS-CoV-2 exhibits neurotropic properties and causes neurological diseases. Here, we review the literature on neurological involvement in SARS-CoV-2 infections and the possible mechanisms of invasion of the nervous system by this virus, to provide a summary and critical analysis of the early reporting of neurological involvement in COVID-19. An exhaustive search of scientific articles on neurological involvement in COVID-19 was performed in the Web of Science, Scopus, Medline/PubMed, and several other databases. Nineteen relevant articles that had been published or were in preprint were carefully selected according to the inclusion and exclusion criteria. Based on our research, we found that patients with COVID-19 can present with neurological symptoms that can be broadly divided into central nervous system involvement, such as headache, dizziness, altered mental state, and disorientation, and peripheral nervous system involvement, such as anosmia and hypogeusia. Most of these patients are in the older age group and exhibit comorbidities, especially hypertension, and severe infection. In extreme presentations of COVID-19, some patients exhibit seizures, stroke, flaccid paraparesis, corticospinal weakness, and even coma. Moreover, the neurological man­ifestations can occur independently of the respiratory system. In conclusion, SARS-CoV-2 infection can cause multiple neurological syndromes in a more complex presentation. Therefore, this review elucidated the involvement of the nervous system in SARS-CoV-2 infection and will hopefully help improve the management of COVID-19.</p> 2020-08-03T00:00:00+02:00 Copyright (c) 2020 Alvin Oliver Payus, Constance Liew Sat Lin, Malehah Mohd Noh, Mohammad Saffree Jeffree, Raymond Azman Ali Laryngeal tuberculosis in renal transplant recipients: A case report and review of the literature 2020-06-28T00:42:11+02:00 Fabrizio Cialente Michele Grasso Massimo Ralli Marco de Vincentiis Antonio Minni Griselda Agolli Michele Dello Spedale Venti Mara Riminucci Alessandro Corsi Antonio Greco <p>Renal allograft recipients are at greater risk of developing tuberculosis than the general population. A woman with a kidney transplant was admitted to our emergency department with high temperature, dysphonia, odynophagia, and asthenia. The final diagnosis was laryngeal tuberculosis. Multidisciplinary collaboration enabled accurate diagnosis and successful treatment. Laryngeal tuberculosis should be considered in renal allograft recipients with hoarseness. A more rapid diagnosis of tuberculosis in renal transplant recipients is desirable when the site involved, such as the larynx, exhibits specific manifestations and the patient exhibits specific symptoms. In these cases, prognosis is excellent, and with adequate treatment a complete recovery is often achieved.</p> 2020-08-03T00:00:00+02:00 Copyright (c) 2020 Fabrizio Cialente, Michele Grasso, Massimo Ralli, Marco de Vincentiis, Antonio Minni, Griselda Agolli, Michele Dello Spedale Venti, Mara Riminucci, Alessandro Corsi, Antonio Greco The first two months of the COVID-19 pandemic in Bosnia and Herzegovina: Single-center experience 2020-07-04T21:17:27+02:00 Jurica Arapović Siniša Skočibušić <p>The novel coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still progressing and has been recorded in more than 210 countries and territories worldwide. In Bosnia and Herzegovina, the first cases of COVID- 19 were detected on March 5, 2020 in the entity of the Republic of Srpska and on March 9, 2020 in the entity of the Federation of Bosnia and Herzegovina. By May 16, 2020, more than 2,200 COVID-19 cases had been recorded in both entities, with a mortality rate of 5.8% (131 of 2,231 cases). The aim of this ongoing study is to present the current epidemiological and sociodemographic parameters of 380 COVID-19 patients diagnosed at the University Clinical Hospital Mostar (UCH Mostar) during the first two months of the COVID-19 pandemic. Of those 380 patients, 60 (15.8%) required hospitalization. The mortality rate was 5% (19/380). The highest mortality rate (15.2%, 12/79) was recorded in the patients aged ≥65 years. In addition to this single-center experience of the ongoing COVID-19 pandemic, we discuss the epidemiological mea­sures imposed in Bosnia and Herzegovina, with an emphasis on the restrictive measures. The COVID-19 pandemic is still ongoing in Bosnia and Herzegovina.</p> 2020-08-03T00:00:00+02:00 Copyright (c) 2020 Jurica Arapović , Siniša Skočibušić Dihydromyricetin promotes autophagy and attenuates renal interstitial fibrosis by regulating miR-155-5p/PTEN signaling in diabetic nephropathy 2020-06-28T00:42:11+02:00 Liming Guo Kuibi Tan Qun Luo Xu Bai <p>Diabetic nephropathy (DN) is the most common complication of diabetes and is prone to kidney failure. Dihydromyricetin (DHM) has been reported to have a variety of pharmacological activities. This study aims to explore the effect of DHM on DN and the underlying molecular mechanism. An <em>in vivo</em> DN rat model was established. The degree of renal interstitial fibrosis (RIF) was detected by hematoxylin-eosin (HE) staining, Masson's trichrome staining, and immunohistochemistry (IHC). <em>In vitro</em>, NRK-52E cells were divided into four groups: normal glucose (NG), high glucose (HG), HG+DHM, and HG+rapamycin (autophagy inhibitor). The levels of autophagy- and fibrosis-related proteins were analyzed by western blotting. The expression of miR-155-5p and phosphatase and tensin homolog deleted on chromosome ten (PTEN) and their relationship were assessed by quantitative reverse transcription (qRT)-PCR and dual luciferase reporter gene assay. Our results showed that RIF was increased in DN rat model and in HG-induced NRK-52E cells. DHM treatment attenuated the increased RIF and also increased autophagy. MiR-155-5p expression was increased, while PTEN expression was decreased in DN rat and cell model, and DHM reversed both effects. Dual luciferase assay showed that PTEN was the target gene of miR-155-5p. DHM inhibited HG-induced fibrosis and promoted autophagy by inhibiting miR-155-5p expression in NRK-52E cells. In addition, DHM promoted autophagy by inhibiting the PI3K/AKT/mTOR signaling pathway. In conclusion, DHM promotes autophagy and attenuates RIF by regulating the miR-155-5p/PTEN signaling and PI3K/AKT/mTOR signaling pathway in DN.</p> 2020-08-03T00:00:00+02:00 Copyright (c) 2020 Authors Diagnostic performance of LI-RADS version 2018 in differentiating hepatocellular carcinoma from other hepatic malignancies in patients with hepatitis B virus infection 2020-06-28T00:42:11+02:00 Shuo Shao Yingying Liang Sichi Kuang Jingbiao Chen Qungang Shan Hao Yang Yao Zhang Bin Wang Kathryn J. Fowler Jin Wang Claude B. Sirlin <p>The diagnostic performance of the Liver Imaging Reporting and Data System (LI-RADS) in differentiating hepatocellular carcinoma (HCC) from other hepatic malignancies has not been investigated in Chinese patients with chronic liver disease from hepatitis B virus (HBV) infection. The aim of this study was to evaluate the accuracy of the LI-RADS version 2018 in differentiating HCC, intrahepatic cholangiocarcinoma (ICCA), and combined HCC-cholangiocarcinoma (cHCC-CCA) in Chinese patients with HBV infection. Seventy consecutive HBV-infected patients with ICCA (n = 48) or cHCC-CCA (n = 22) who underwent contrast-enhanced magnetic resonance imaging (CE-MRI) between 2006 and 2017 were enrolled along with a comparison cohort of 70 patients with HCC and CE-MRI-matched for tumor size (10–19 mm, 20–30 mm, 31–50 mm, and &gt;50 mm). Imaging feature frequencies for each tumor type were compared using Fisher’s exact test. The classification accuracy of LR-5 and LR-M was estimated for HCC versus non-HCC (ICCA and cHCC-CCA). The interobserver agreement was good for LI-RADS categories of HCC and moderate for non-HCC. After consensus read, 66 of 70 (94%) HCCs were categorized LR-5 (including tumor in vein [TIV] with LR-5), while 42 of 48 (88%) ICCAs and 13 of 22 (59%) cHCC-CCAs were categorized LR-M (including TIV with LR-M) (<em>p</em> &lt; 0.001). Thus, assignment of LR-5 provided 94% sensitivity and 81% specificity for HCC. LR-M provided 79% sensitivity and 97% specificity for non-HCC (ICCA and cHCC-CCA); and the sensitivity and accuracy were lower in differentiating HCC from non-HCC (tumor size &lt;20 mm). LI-RADS v2018 category 5 and M reliably differentiated HBV-related HCC from ICCA. However, a substantial proportion of cHCC-CCAs were categorized LR-5 rather than LR-M. While management is controversial for these combined tumors, accurate prospective differentiation is desired for optimal treatment.</p> 2020-08-03T00:00:00+02:00 Copyright (c) 2020 Shuo Shao, Yingying Liang, Sichi Kuang, Jingbiao Chen, Qungang Shan, Hao Yang, Yao Zhang, Bin Wang, Kathryn J. Fowler, Jin Wang, Claude B. Sirlin The role of cytoreductive nephrectomy in renal cell carcinoma patients with liver metastasis 2020-07-29T12:06:07+02:00 Boda Guo Shengjing Liu Miao Wang Huimin Hou Ming Liu <p>It is widely accepted that renal cell carcinoma (RCC) with liver metastasis (LM) carries a dismal prognosis. We aimed to explore the value of cytoreductive nephrectomy among these patients. Patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2017. The univariate and multivariate Cox proportional hazards models were conducted to select the prognostic predictors of survival. Patients were divided into nephrectomy and non-nephrectomy groups. Propensity score-matching (PSM) analyses were applied to reduce the above factors’ differences between the groups. Overall survival (OS) was compared by Kaplan–Meier analyses. Data from 683 patients were extracted from the database. The univariate Cox regression and multivariate Cox regression revealed that factors including age, histologic type, T and N stages, lung metastasis, brain metastasis, and nephrectomy were significant predictors of survival in the patients. After the PSM analyses, we found that nephrectomy prolonged OS. Nephrectomy can prolong OS in eligible RCC patients with LM.</p> 2020-07-23T09:52:22+02:00 Copyright (c) 2020 Boda Guo, Shengjing Liu, Miao Wang, Huimin Hou, Ming Liu Clinical applications of avian eggshell-derived hydroxyapatite 2020-07-27T07:29:08+02:00 Horia Opris Simion Bran Cristian Dinu Mihaela Baciut Daiana Antoaneta Prodan Alexandru Mester Grigore Baciut <p>The search for bone reconstruction materials and methods is an ongoing challenge. The aim of this review is to systemically search the available literature concerning the clinical performance of eggshell as a substitute material in guided bone regeneration in oral surgery. Five databases (PubMed, Cochrane, Web of Science, Scopus, and Embase) were searched up to February 2020. Clinical trials that used eggshell as a bone substitute material were included in the review. Animal and <em>in vivo</em> studies were excluded from the review. ROBINS-I was used to evaluate the risk of bias. A total of 840 studies were retrieved, out of which 55 full-text articles were screened. Five studies were finally included: one study showed critical and four serious risk of bias. A total of 74 patients and 88 intervention sites were included in the five studies. Clinical and radiological evaluation showed complete healing during the follow-ups. Statistically significant radiological and clinical evidence of new bone formation was achieved for socket preservation, grafting after third molar extraction, and cystic/apicectomy grafting. One patient with complications was reported. Histological analysis and micro computed tomography confirmed that it promotes bone regeneration. A comparison with synthetic hydroxyapatite showed similar healing characteristics. Within the limitations of the included studies, the eggshell can be safely and efficiently used in guided bone regeneration procedures, but more research is needed to completely evaluate the full potential of this material.</p> 2020-07-07T07:34:12+02:00 Copyright (c) 2020 Horia Opris, Simion Bran, Cristian Dinu, Mihaela Baciut, Daiana Antoaneta Prodan, Alexandru Mester, Grigore Baciut Dose-dependent effects of adalimumab in neonatal rats with hypoxia/reoxygenation-induced intestinal damage 2020-07-20T07:29:17+02:00 Halil Kocamaz Özmert MA Özdemir Nilay Şen Türk Yaşar Enli Barbaros Şahin Hacer Ergin <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> 2020-07-03T17:07:02+02:00 Copyright (c) 2020 Halil Kocamaz, Özmert MA Özdemir, Nilay Şen Türk, Yaşar Enli, Barbaros Şahin, Hacer Ergin Association of polymorphisms in TP53 and the promoter region of IL10 with gastric cancer in a Kazakh population 2020-07-22T06:59:17+02:00 Gulmira Kulmambetova Ivan Shtefanov Akbota Aitkulova Meruyert Imanbekova Aisha Iskakova Abay Makishev Yerlan Ramankulov <p>The emerging evidence indicates that single nucleotide polymorphisms (SNPs) of the tumor necrosis factor (<em>TNF</em>), interleukin 10 (<em>IL10</em>), tumor protein p53 (<em>TP53</em>), and cluster of differentiation 14 (<em>CD14</em>) genes may determine individual susceptibility to gastric cancer (GC). We aimed to investigate the associations for polymorphisms of the <em>TNF</em>, <em>IL10</em>, <em>TP53</em>, and <em>CD14</em> genes in a population of Kazakhs, to identify potential risk or protective associations of the SNPs with GC. A case group of 143 patients hospitalized for GC was enrolled. Controls were 355 volunteers with no history of any cancer and frequency matched with cases by age. Differences in proportions for categorical variables and the assessment of genotypic frequencies conforming to the Hardy–Weinberg equilibrium law were evaluated by the Chi-square test. Associations between genetic polymorphisms and the risk of GC were estimated by regression analysis. For genetic analysis, three genetic models (additive, dominant, and recessive) were used. Four significant associations were found. The SNPs rs1042522 of <em>TP53</em> and rs1800896 of <em>IL10</em> were risk factors for GC by the additive model. Two polymorphisms of <em>IL10</em> were protective of GC, namely, rs1800872 by additive model and rs1800871 by recessive model. No significant associations were observed between the <em>TNF</em> and <em>CD14</em> polymorphisms and GC. The polymorphisms <em>TP53</em> rs1042522 and <em>IL10</em> rs1800896 are associated with GC risk, while the polymorphisms <em>IL10</em> rs1800872 and rs1800871 are protective of GC in the population of Kazakhs.</p> 2020-07-03T10:03:06+02:00 Copyright (c) 2020 Gulmira Kulmambetova, Ivan Shtefanov, Akbota Aitkulova, Meruyert Imanbekova, Aisha Iskakova, Abay Makishev, Yerlan Ramankulov