Bosnian Journal of Basic Medical Sciences 2020-05-26T16:34:38+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> Lingual cyst with respiratory epithelium: The importance of differential diagnosis 2020-05-26T16:34:38+02:00 Fabrizio Cialente Giulia De Soccio Vincenzo Savastano Michele Grasso Michele Dello Spedale Venti Massimo Ralli Mara Riminucci Marco de Vincentiis Alessandro Corsi Antonio Minni <p>Lingual cyst with respiratory epithelium (LCRE) is a very rare congenital cyst of the tongue, floor of the mouth, pharynx or hypopharynx with 21 cases reported in the literature (1, 2). Differential diagnosis is very important for patients presenting with lingual cysts, as this may impact treatment and follow-up. LCRE should be included in the different diagnosis of dermoid cyst (3), teratoid cyst (4), epidermoid cyst (5), thyroglossal duct cyst (6), lymphoepithelial cyst (7), mucocele or ranula (8). Each entity has a peculiar histologic presentation, although the clinical aspect may be very similar (1). The dermoid cyst is lined by a keratinized squamous epithelium and contains skin appendages in the cyst. Epidermoid cyst is similar to the dermoid cyst but is characterized by non-keratinized squamous epithelium and has a lumen filled of keratin. Teratoid cyst contains derivatives of the endoderm, ectoderm and/or mesoderm. The thyroglossal duct cyst is usually lined by columnar, stratified squamous epithelium, or an intermediate transition type of epithelium, with the mandatory presence of thyroid tissue in the cyst wall. Lymphoepithelial cyst is identified by the presence of the lymphoid aggregates in the cyst wall. A mucous retention cyst, so called mucocele or ranula, contains mucin and granulation tissue (1).</p> <p>Read the full text <a href=""><strong>[PDF]</strong></a></p> 2020-05-26T16:16:51+02:00 Copyright (c) 2020 Fabrizio Cialente, Giulia De Soccio, Vincenzo Savastano, Michele Grasso, Michele Dello Spedale Venti, Massimo Ralli, Mara Riminucci, Marco de Vincentiis, Alessandro Corsi, Antonio Minni Lessons learned from COVID-19 pandemic in Italy 2020-05-21T18:53:47+02:00 Antonio Minni Massimo Ralli Francesca Candelori Fabrizio Cialente Lucia Ercoli Claudio Parlapiano Antonio Greco Marco de Vincentiis <p>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 healthcare 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 devices,&nbsp; 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 accesses to hospital emergency departments and the related spread of the infection.</p> 2020-05-16T14:05:40+02:00 Copyright (c) 2020 Antonio Minni, Massimo Ralli, Francesca Candelori, Fabrizio Cialente, Lucia Ercoli, Claudio Parlapiano, Antonio Greco, Marco de Vincentiis 2020 consensus guideline for optimal approach to the diagnosis and treatment of HER2-positive breast cancer in Bosnia and Herzegovina 2020-05-18T09:55:07+02:00 Semir Bešlija Zdenka Gojković Timur Cerić Alma Mekić Abazović Inga Marijanović Semir Vranić Jasminka Mustedanagić–Mujanović Faruk Skenderi Ivanka Rakita Aleksandar Guzijan Dijana Koprić Alen Humačkić Danijela Trokić Jasmina Alidžanović Alma Efendić Ibrahim Šišić Harun Drljević Vanesa Bešlagić Božana Babić Azra Pašić Anela Ramić Dijana Mikić Zlatko Guzin Dragana Karan Teo Buhovac Dragana Miletić Senad Šečić Azra Đozić Šahmić Lejla Mujbegović Alisa Kubura Mensura Burina Nenad Lalović Nikolina Dukić Jelena Vladičić Mašić Mirjana Ćuk Rajna Stanušić <p>The HERe2cure project, which involved a group of breast cancer experts, members of multidisciplinary tumor boards from healthcare institutions in Bosnia and Herzegovina, was initiated with the aim of defining an optimal approach to the diagnosis and treatment of HER2 positive breast cancer. After individual multidisciplinary consensus meetings were held in all oncology centers in Bosnia and Herzegovina, a final consensus meeting was held in order to reconcile the final conclusions discussed in individual meetings. Guidelines were adopted by consensus, based on the presentations and suggestions of experts, which were first discussed in a panel discussion and then agreed electronically between all the authors mentioned. The conclusions of the panel discussion represent the consensus of experts in the field of breast cancer diagnosis and treatment in Bosnia and Herzegovina. The objectives of the guidelines include the standardization, harmonization and optimization of the procedures for the diagnosis, treatment and monitoring of patients with HER2-positive breast cancer, all of which should lead to an improvement in the quality of health care of mentioned patients. The initial treatment plan for patients with HER2-positive breast cancer must be made by a multidisciplinary tumor board comprised of at least: a medical oncologist, a pathologist, a radiologist, a surgeon, and a radiation oncologist/radiotherapist.</p> 2020-05-16T13:01:48+02:00 Copyright (c) 2020 Semir Bešlija, Zdenka Gojković, Timur Cerić, Alma Mekić Abazović, Inga Marijanović, Semir Vranić, Jasminka Mustedanagić–Mujanović; Faruk Skenderi; Ivanka Rakita, Aleksandar Guzijan, Dijana Koprić, Alen Humačkić, Danijela Trokić, Jasmina Alidžanović, Alma Efendić, Ibrahim Šišić, Harun Drljević, Vanesa Bešlagić, Božana Babić, Azra Pašić, Anela Ramić, Dijana Mikić, Zlatko Guzin, Dragana Karan, Teo Buhovac, Dragana Miletić, Senad Šečić, Azra Đozić Šahmić, Lejla Mujbegović, Alisa Kubura, Mensura Burina, Nenad Lalović, Nikolina Dukić, Jelena Vladičić Mašić, Mirjana Ćuk, Rajna Stanušić Respiratory depression in the post-anesthesia care unit: Mayo Clinic experience 2020-05-19T17:22:39+02:00 Mariana L. Laporta Juraj Sprung Toby N. Weingarten <p>The anesthesia recovery is a complex physiologic process as systems recover from the effects of surgery and anesthesia. Inadequate recovery of respiratory physiology can lead to severe hypoxemia-induced end-organ damage and even death. Emerging evidence suggests that signs of respiratory depression during early anesthesia recovery may portend increased risk for future severe adverse events. This article briefly reviews the Mayo Clinic research experience and advances in clinical practice. From the implementation of a step-down model of discharge criteria in the post-anesthesia care unit (PACU), consisting of PACU nurses monitoring patients in predetermined periods for signs of respiratory depression, and delaying PACU discharge for patients who exhibit signs of respiratory depression, and early intervention in high-risk patients. Subsequent studies found that even a single episode of respiratory depression in the PACU was strongly associated with subsequent respiratory complications. Further, patient baseline characteristics found to be associated with respiratory depression included obstructive sleep apnea and low body weight, and surgical factors associated with increased risk included the use of preoperative sustained-release opioids, perioperative gabapentinoid use, higher intraoperative opioids, isoflurane as the volatile anesthetic, and longer surgical duration. Based in part of Mayo Clinic research, the FDA issued a warning in 2019 on gabapentinoids use and respiratory complications, increasing the recommended level of respiratory vigilance in patients using this medication. Understanding the complex nature of postoperative respiratory events requires a range of translational and clinical research and constant update of practice.</p> 2020-05-13T12:53:13+02:00 Copyright (c) 2020 Mariana L. Laporta, Juraj Sprung, Toby N. Weingarten Clinical management of chronic mercury intoxication secondary to skin lightening products: A proposed algorithm 2020-05-16T17:01:24+02:00 Fitri Fareez Ramli <p>Mercury is a toxic substance that is commonly used in skin lightening products. Various effects on humans have been observed, which affect both users and non-users. Many cases reported delayed diagnosis and treatment, even after weeks of hospitalization. The possible reasons are non-specific clinical manifestation and lack of awareness and knowledge regarding chronic mercury intoxication secondary to skin lightening products. A thorough history of mercury exposure is crucial. Physical assessment and relevant supporting tests are indicated to establish a diagnosis. Blood and urine mercury levels are an essential examination for diagnosis and monitoring of the progress and response to treatment. The primary treatment is the discontinuation of the skin lightening products. Chelation therapy is not mandatory and usually indicated for symptomatic patients. The prognosis depends on the duration of the product use, concentration of mercury in the skin product, and the severity of the clinical presentation.</p> 2020-05-13T11:03:19+02:00 Copyright (c) 2020 Fitri Fareez Ramli A three-dimensional computed tomography study to determine the ideal method for fluoroscopically-guided bone marrow aspiration from the iliac crest 2020-05-14T19:22:23+02:00 Ryan S. D'Souza Langping Li Shuai Leng Christine Hunt Luke Law Casey Muir Jason Eldrige Mohamad Bydon Meng Chi Shane Shapiro William D. Mauck Wenchun Qu <p>Bone marrow aspiration (BMA) through the iliac crest is potentially unsafe due to the vicinity of neurovascular structures in the greater sciatic notch. Our objective was to investigate the safety of a recently described BMA technique, specifically a trajectory from the posterior superior iliac spine (PSIS) to the anterior inferior iliac spine (AIIS). We conducted a chart review of 260 patients, analyzing three-dimensional reconstructed computed tomography images of the pelvis and sacrum to validate that this new approach offers a wide safety margin from the greater sciatic notch. Analysis of three-dimensional computed tomography scans demonstrated that the PSIS to AIIS trajectory never crossed the greater sciatic notch. The trajectory was noted to be at least one cm away from the greater sciatic notch in all measurements. The new trajectory entered the PSIS at 25.29 ± 4.34° (left side) and 24.93 ± 4.15° (right side) cephalad from the transverse plane, and 24.58 ± 4.99° (left side) and 24.56 ± 4.67° (right side) lateral from the mid-sagittal plane. The area of bone marrow encountered with the new approach was approximately 22.5 cm<sup>2</sup>. Utilizing the same CT scans, the trajectory from the traditional approach crossed the greater sciatic notch in all scans, highlighting the potential for violating the greater sciatic notch boundary and damaging important neurovascular structures. Statistically significant sex-related differences were identified in needle trajectory angles for both approaches. We conclude that based on this three-dimensional computed tomography study, a trajectory from the PSIS to the AIIS for BMA may offer a wide safety margin from the greater sciatic notch.</p> 2020-05-11T15:19:06+02:00 Copyright (c) 2020 Ryan S. D'Souza, Langping Li, Shuai Leng, Christine Hunt, Luke Law, Casey Muir, Jason Eldrige, Mohamad Bydon, Meng Chi, Shane Shapiro, William D. Mauck, Wenchun Qu Clinical Nocardia species: Identification, clinical characteristics, and antimicrobial susceptibility in Shandong, China 2020-05-22T05:30:57+02:00 Shu-Hua Lu Zhen-Wen Qian Pei-Pei Mou Lian Xie <p><em>Nocardia</em> is a pathogen responsible for a variety of clinical infections. Here, we aimed to investigate the species distribution, clinical manifestations, and antimicrobial susceptibility of <em>Nocardia</em> species in two tertiary general hospitals over 3 years in China. In this retrospective study, a total of 27 <em>Nocardia</em> species were isolated from 27 individuals between January 2017 and December 2019. <em>Nocardia</em> isolates were identified to species level by mass spectrometry and 16S rRNA PCR sequencing. Clinical data were collected from medical records. Antimicrobial susceptibility was determined by standard Broth microdilution method. The 27 patients with <em>Nocardia</em> infection included 12 males and 15 females with a mean age of 60.11 years. Among 27 <em>Nocardia</em> isolates, 7 species were identified, with the most common species being <em>N. otitidiscaviarum</em> (40.7%). The antimicrobial susceptibility profiles varied between different <em>Nocardia</em> species. Notably, all<em> Nocardia</em> isolates were linezolid susceptible. Majority of <em>Nocardia</em> isolates were collected from a department of respiratory medicine (55.56%) and sputum specimen (44.44%). Pulmonary region was the most involved body site (70.37%), followed by skin (7.4%) and pleural cavity (7.4%). Most patients with <em>Nocardia</em> infection needed combination antibiotic therapy. Two deaths were reported during the treatment period and 24 patients achieved improvement after antibiotic therapy. The clinical manifestations of <em>Nocardia</em> infection and antimicrobial susceptibility profiles varied with diverse <em>Nocardia</em> species. Thus, the accurate identification of these species is crucial for the diagnosis and the selection of antibiotic treatment.</p> 2020-05-05T11:16:55+02:00 Copyright (c) 2020 Shu-Hua Lu, Zhen-Wen Qian, Pei-Pei Mou, Lian Xie Progress in research on childhood T-cell acute lymphocytic leukemia, Notch1 signaling pathway, and its inhibitors: A review 2020-05-26T16:27:58+02:00 Zhong Fang-Fang Yang You Liu Wen-Jun <p>Childhood leukemia is a cancer that seriously threatens the life of children in China. Poor sensitivity to chemotherapy, and susceptibility to drug resistance are the reasons for treatment of T-cell acute lymphocytic leukemia (T-ALL) being extremely difficult. Moreover, traditional intensive chemotherapy regimens cause great damage to children. Therefore, it is highly important to search for the targeted drugs and develop precise individualized treatment for child patients. There are activating mutations in the <em>NOTCH1</em> gene in more than 50% of human T-ALLs, and the Notch signaling pathway is involved in the pathogenesis of T-ALL. In this review, we summarize the progress in research on T-ALL and Notch1 signaling pathway inhibitors to provide a theoretical basis for the clinical treatment of T-ALL.</p> 2020-05-04T06:55:28+02:00 Copyright (c) 2020 Zhong Fang-Fang, Yang You, Liu Wen-Jun P2X7 receptor as an independent prognostic indicator in gastric cancer 2020-04-30T22:41:55+02:00 Ilknur Calik Muhammet Calik Burcu Sarikaya Ibrahim Hanifi Ozercan Ramazan Arslan Gokhan Artas Adile Ferda Dagli <p>Gastric cancer (GC) is one of the foremost causes of cancer-related death around the world. The P2X7 receptor (P2X7R), a member of the P2X7R subfamily of P2 receptors, is a unique molecule that has been shown to affect tumor growth and progression as well as various inflammatory processes, including proliferation of T lymphocytes, release of cytokines, and production of free oxygen radicals. P2X7R has been established as a prognostic parameter in some cancers, and recently, it has been investigated in the development of new targeted therapies. In the present study, we aimed to investigate the prognostic value of P2X7R expression in GC. The expression profile of P2X7R was evaluated immunohistochemically in 156 paraffin-embedded human GC specimens. P2X7R expression was higher in patients with lymph node metastasis than in those without (<em>p </em>&lt; 0.001). P2X7R overexpression was closely related with tumor-infiltrating lymphocytes (TILs) (<em>p </em>= 0.001), vascular invasion (<em>p </em>= 0.006), depth of invasion (<em>p </em>&lt; 0.001), distant metastasis (<em>p </em>&lt; 0.001), and advanced tumor, node, metastasis stage (<em>p </em>&lt; 0.001). Moreover, univariate (hazard ratio [HR] 3.98; 95% confidence interval (CI) 1.89-11.82; <em>p </em>&lt; 0.001) and multivariate (HR 2.24; 95% CI 3.53-12.50; <em>p </em>&lt; 0.001) Cox regression analysis showed that upregulated P2X7R expression clearly correlated with worsened overall survival. In summary, our data revealed that P2X7R may serve as a reliable prognostic parameter and promising therapeutic target for GC.</p> 2020-05-01T00:00:00+02:00 Copyright (c) 2020 Ilknur Calik, Muhammet Calik, Burcu Sarikaya, Ibrahim Hanifi Ozercan, Ramazan Arslan, Gokhan Artas, Adile Ferda Dagli Inflammatory cells in perivascular adipose tissue and the integrity of the tunica media in atherosclerotic coronary arteries 2020-04-30T22:41:55+02:00 Ruda Zorc-Pleskovič Marjeta Zorc Dušan Šuput Aleksandra Milutinović <p>Obstructive coronary artery disease (CAD) is characterized by inflammation within the atherosclerotic coronary arteries. Infiltration of inflammatory cells into muscular media can lead to remodeling and weakening of the arterial wall. We examined the relationship between inflammatory infiltration in perivascular adipose tissue (PVAT), state of the external elastic membrane, and the intensity of inflammatory infiltration in the tunica media of coronary arteries obtained by endarterectomy from symptomatic patients with diffuse CAD. We analyzed endarterectomy sequesters from 22 coronary arteries that contained the intima, media, a part of the adventitia, and PVAT in at least one part of the sequester. The coronary arteries were divided into two groups according to the presence or absence of inflammatory infiltration in PVAT. Staining with hematoxylin-eosin and by the Movat's method showed atherosclerotic changes in the intima and media. Immunohistochemistry (anti-leukocyte common antigen [LCA] antibody) was used for the detection of leukocytes. We found a significant positive correlation between inflammatory infiltration in PVAT and preservation of the external elastic membrane of coronary arteries. Furthermore, we found a significant negative correlation between inflammatory infiltration in PVAT and the intensity of inflammatory infiltration in the media. It seems that the integrity of the external elastic membrane and the proinflammatory properties of PVAT restrain inflammatory cells within PVAT. Both effects may prevent the migration of inflammatory cells into the media and delay the development of CAD.</p> 2020-05-01T00:00:00+02:00 Copyright (c) 2019 The effects of mutational profiles on phenotypic presentation of myeloproliferative neoplasm subtypes in Bosnia: 18 year follow-up 2020-04-30T22:41:57+02:00 Amina Kurtovic-Kozaric Erna Islamagic Hana Komic Nurija Bilalovic Izet Eminovic Adnan Burekovic Amna Uzunovic Sabira Kurtovic <p>The identification of mutually exclusive somatic mutations shared among myeloproliferative neoplasm (MPN) subtypes has provided a powerful tool for studying disease evolution. Clinical features, gene mutations, and survival over 18 years were analyzed in MPN patients. One hundred thirty-eight MPN patients were subcategorized according to MPN subtypes: essential thrombocythemia (ET, n = 41), polycythemia vera (PV, n = 56), primary myelofibrosis (PMF, n = 10), and MPN unclassified (MPN-U, n = 31). Patient characteristics included clinical parameters, overall survival (OS), and mutational status of the Janus kinase 2 (<em>JAK2</em>), calreticulin (<em>CALR</em>), and myeloproliferative leukemia virus oncogene (<em>MPL</em>) genes. We compared hematologic and clinical features of <em>JAK2</em><sup>V617F</sup>-ET vs. <em>CALR</em>-mutated ET vs. <em>JAK2</em><sup>V617F</sup>-PV patients. <em>JAK2</em><sup>V617F</sup>-patients had higher values of erythrocytes, hemoglobin, and hematocrit compared to <em>CALR</em>-mutated patients (<em>p</em> &lt; 0.05). The mutant allele burden in <em>JAK2</em><sup>V617F</sup>-PV and <em>JAK2</em><sup>V617F</sup>-ET patients directly correlated with erythrocyte, hemoglobin, and hematocrit values, but it inversely correlated with platelet count. Thus, mutant allele burden was an indicator of the clinical phenotype in <em>JAK2</em><sup>V617F</sup>-MPN patients. OS was not affected by the mutational status. In general, mutated <em>JAK2</em>, <em>CALR</em>, and <em>MPL</em> genes left specific hematological signatures.</p> 2020-05-01T00:00:00+02:00 Copyright (c) 2019 Serum patterns of mir-23a and mir-181b in irritable bowel syndrome and colorectal cancer - A pilot study 2020-04-30T22:41:58+02:00 Alexandra Chira Mihai-Stefan Muresan Cornelia Braicu Liviuta Budisan Lajos Raduly Romeo Ioan Chira Dan Lucian Dumitrascu Ioana Berindan-Neagoe <p>Emerging evidence demonstrates that microRNAs (miRNAs) could serve as reliable biomarkers of inflammation and oncogenesis. The aim of this study was to determine whether miR-23a and miR-181b were suitable as biomarkers of irritable bowel syndrome (IBS) and colorectal cancer (CRC). Forty patients with IBS (29 females, 11 males), 33 with CRC (14 females, 19 males), and 33 healthy controls (17 females, 16 males) were prospectively included. Serum levels of miRNAs were evaluated by quantitative real-time PCR. The serum levels of miR-23a and miR-181b were significantly higher in the IBS group (<em>p</em>&nbsp;=&nbsp;0.0009 and 0.004, respectively) and CRC group (<em>p</em>&nbsp;=&nbsp;0.002 and 0.029, respectively) than in the control group. Serum levels of miR-23a and miR-181b were upregulated in CRC vs. IBS, but the differences did not reach statistical significance (<em>p</em>&nbsp;=&nbsp;0.169 and 0.179, respectively). The miRNet and Reactome databases identified phosphatase and tensin homolog as a major common pathway, indicating inflammation as a central hallmark. Although miRNAs could serve as reliable biomarkers in clinical practice, future studies are needed to establish appropriate cut-off limits.</p> 2020-05-01T00:00:00+02:00 Copyright (c) 2019 Prognostic role of NLR, PLR, and LMR in patients with pulmonary embolism 2020-04-30T22:41:58+02:00 Nuri Köse Tarık Yıldırım Fatih Akın Seda Elçim Yıldırım İbrahim Altun <p>Pulmonary embolism (PE) is associated with significant morbidity and mortality. New biological markers are being investigated for estimating the prognosis of PE patients. Since PE is closely associated with inflammatory status, the neutrophil-lymphocyte (NLR), platelet-lymphocyte (PLR), and lymphocyte-monocyte (LMR) ratios were suggested to be useful in predicting patient outcomes. This study aimed to evaluate the prognostic role of NLR, PLR, and LMR in PE. A total of 103 PE cases from a cardiology department were included in the study. We retrospectively evaluated demographic and clinical characteristics, treatments, laboratory and imaging findings, and outcomes of patients. The median follow-up of PE patients was 39 months, and the 5-year overall survival probability was 73.8%. Out of 103 patients, 20 were classified as high risk PE cases (19.4%). Thrombolytic treatment was administered to 23 patients (22.3%). Systolic pulmonary arterial pressure was measured during one year, showing a significant decrease from 51.7 ± 15.7 mmHg at admission to 26.6 ± 4.0 mmHg at first year assessment. Age (OR: 1.06, <em>p</em> &lt; 0.001) and NLR (OR: 1.52, <em>p</em> &lt; 0.0019) were significantly associated with the disease status. The independent prognostic factors in moderate-low and low risk PE groups were NLR (HR: 1.17, <em>p</em> = 0.033) and LMR (HR: 1.58, <em>p</em> = 0.046). In moderate-high and high risk PE patients, the independent prognostic factors were age (HR: 1.07, <em>p</em> = 0.014) and PLR (HR: 1.01, <em>p</em> = 0.046). NLR, PLR, and LMR were associated with the prognosis of PE patients. The clinical severity of PE should be considered when utilizing these markers to assess patient outcomes.</p> 2020-05-01T00:00:00+02:00 Copyright (c) 2019 A preliminary study of microRNA expression in different types of primary melanoma 2020-04-30T22:41:56+02:00 Ioana Gencia Flavia Baderca Stefania Avram Armand Gogulescu Anca Marcu Edward Seclaman Catalin Marian Caius Solovan <p>MicroRNAs (miRNAs) have been proven to regulate the development and progression of cancer through various mechanisms. The aim of the present study was to compare miRNA expression between primary melanomas from different sites. We analyzed the expression of 84 miRNAs in 27 primary melanoma and 5 nevus formalin-fixed paraffin-embedded (FFPE) samples using the Human Cancer PathwayFinder miScript miRNA PCR Array. The FFPE samples were obtained from the archives of the Municipal Clinical Emergency Hospital of Timisoara and included 10 cutaneous melanomas, 10 uveal melanomas, 7 mucosal melanomas, and 5 cutaneous nevi. Out of 84 miRNAs, 11 miRNAs showed altered expression in all types of melanoma compared with the nevi. Among these, miR-155-5p, miR-9-5p, miR-142-5p, miR-19a-3p, miR-134-5p, and miR-301a-3p were upregulated, while miR-205-5p, miR-203a-3p, miR-27b-3p, miR-218-5p, and miR-23b-3p were downregulated. The highest similarity in miRNA expression pattern was found between uveal and mucosal melanoma groups, i.e., 15 miRNAs had altered expression in both groups. Overall, we identified several miRNAs with significantly altered expression in primary melanomas, including those reported for the first time in this type of cancer. Among them, mir-9-5p, mir-203a-3p, mir-19a-3p, mir-27b-3p, and mir-218-5p showed altered expression in all three melanoma types vs. nevi. Further research should explore the potential of these miRNAs in melanoma.</p> 2020-05-01T00:00:00+02:00 Copyright (c) 2019 Mesenchymal stem cells from bone marrow regulate invasion and drug resistance of multiple myeloma cells by secreting chemokine CXCL13 2020-04-30T22:41:56+02:00 Guihua Zhang Faan Miao Jinge Xu Rui Wang <p>Multiple myeloma (MM) is a hematologic cancer arising from plasma cells. Mesenchymal stem cells (MSCs) are a heterogeneous cell population in the bone marrow microenvironment. In this study, we evaluated the regulatory effects of MSCs on the invasion and drug resistance of MM cells U266 and LP-1. Bone marrow samples from MM patients and healthy subjects were collected. MSCs were extracted from bone marrow and cultured, and their phenotypes were identified by flow cytometry. The level of CXCL13 in the supernatant of cultured MSCs was detected by ELISA. The protein expression of CXCR5 (a specific receptor of CXCL13) in U266 and LP-1 cells was detected by Western blot. The effects of MSCs on the invasion of U266 and LP-1 cells and the resistance to bortezomib were assessed by Transwell and CCK-8 assay, respectively. The mRNA and protein expressions of BTK, NF-κB, BCL-2, and MDR-1 were detected by RT-PCR and Western blot, respectively. CXCL13 was secreted by MSCs in the bone marrow microenvironment, and the level in MSCs from MM patients was significantly higher than that of healthy subjects. CXCR5 was expressed in both U266 and LP-1 cells. The resistance of MM cells to bortezomib was enhanced by MSCs through CXCL13 secretion. The invasion and proliferation of U266 and LP-1 cells were promoted, and the mRNA and protein expressions of BTK, NF-κB, BCL-2, and MDR-1 were upregulated by MSCs. The basic biological functions of MM cells U266 and LP-1 were affected by MSCs via the CXCL13-mediated signaling pathway. This study provides valuable experimental evidence for clinical MM therapy.</p> 2020-05-01T00:00:00+02:00 Copyright (c) 2019 Inhibition of miR-9 decreases osteosarcoma cell proliferation 2020-04-30T22:41:57+02:00 Wu Gang Wei Tanjun Huang Yong Qin Jiajun Zhang Yi Hu Hao <p>Osteosarcoma (OS) is the most common primary bone tumor that affects adolescents and young adults. Disruption of microRNA (miRNA) regulation is well established in the pathophysiology of different cancers, including OS. Increased expression of miR-9 in OS positively correlates with the tumor size, clinical stage, and distant metastasis. In the present study, we used two different OS cell lines, MG-63 and Saos-2, as <em>in vitro</em> models. miR-9 inhibitor and miR-9 mimics were used to study the function of miR-9 in these two cell lines. We determined the effect of miR-9 inhibition on cell proliferation, cell cycle, apoptosis, and the protein expression of different genes. Our results demonstrated that miR-9 inhibition in the human OS cell lines suppresses their metastatic potential, as determined by decreased cell proliferation and cell cycle arrest, decreased invasion, and increased apoptosis. The Western blot analysis showed that E-cadherin, matrix metalloproteinase 13, forkhead box O3, Bcl-2-like protein 11, and β-catenin are involved in miR-9 signaling. Moreover, miR-9 mimics rescued the effects caused by the inhibition of miR-9 in the OS cell lines. Our findings suggest that miR-9 is important for mediating OS cell migration, invasion, metastasis, and apoptosis. Inhibition of miR-9 could be further explored as a therapeutic target to treat OS.</p> 2020-05-01T00:00:00+02:00 Copyright (c) 2019 WD-3 inhibits the proliferation of breast cancer cells by regulating the glycolytic pathway 2020-04-30T22:41:57+02:00 Xiaodan Zhu Lu Zhao Jianliang You Yiqun Ni Zhipeng Wei Qing Xue Chunhui Jin <p>Number 3 Prescription (WD-3) is an herbal remedy used in traditional Chinese medicine that has been shown to improve the outcomes of patients with advanced colon and gastric cancers. This study aimed to investigate the effect of WD-3 on proliferation, glycolysis, and hexokinase 2 expression in breast cancer cells. Four breast cancer cell lines (MDA-MB-231, BT-549, MCF-7, and MCF-7/ADR-RES) were treated with different concentrations of WD-3 compared with blank control (phosphate-buffered saline). Each of the breast cancer cell lines was also divided into WD-3, paclitaxel, and blank control group. Cell proliferation and morphology were assessed by MTT assay, nuclear Hoechst 33258 staining, or immunofluorescence. Apoptosis was analyzed by flow cytometry. High performance liquid chromatography was used for measurement of ATP, ADP, and AMP. Hexokinase 2 expression was analyzed by Western blot and quantitative reverse transcription PCR. WD-3 inhibited proliferation and increased apoptosis in all four breast cancer cell lines, in a dose-dependent manner. ATP and EC (energy charge) were significantly decreased in WD-3-treated BT-549 and MDA-MB-231 cells. WD-3 significantly downregulated the protein and mRNA expression of hexokinase II in BT-549 cells, however, not in the other three breast cancer cell lines. Our findings indicate that WD-3 targets the glycolytic pathway in breast cancer cells to exert its antitumor activity.</p> 2020-05-01T00:00:00+02:00 Copyright (c) 2020 Xiaodan Zhu, Lu Zhao, Jianliang You, Yiqun Ni, Zhipeng Wei, Qing Xue, Chunhui Jin The effects of exercise on vascular markers and C-reactive protein among obese children and adolescents: An evidence-based review 2020-04-30T22:41:53+02:00 Norizam Salamt Musilawati Muhajir Amilia Aminuddin Azizah Ugusman <p>Numerous studies have evaluated the effects of exercise training on obese children and adolescents. However, the impact of aerobic and/or resistance exercise alone, without any other interventions, on vascular markers and C-reactive protein (CRP) in obese children and adolescents is still not clear. We performed a literature search in Ovid Medline, PubMed, and SCOPUS databases to identify articles on the effects of exercise on vascular markers and CRP among obese children and adolescents, published between January 2009 and May 2019. Only full-text articles in English that reported on the effect of aerobic and/or resistance exercise on the vascular markers pulse wave velocity (PWV), carotid intima-media thickness (CIMT), flow-mediated dilatation (FMD), augmentation index (AIx), or CRP in obese children and adolescents (5–19 years old) were included. The literature search identified 36 relevant articles; 9 articles that fulfilled all the inclusion criteria were selected by two independent reviewers. Aerobic exercise or a combination of aerobic and resistance exercise training significantly improved CIMT and PWV in obese children and adolescents in all studies in which they were measured (2 studies for PWV and 4 studies for CIMT). However, the effects of exercise on FMD and CRP levels were inconclusive, as only half of the studies demonstrated significant improvements (1/2 studies for FMD and 4/8 studies for CRP). The results of our review support the ability of exercise to improve vascular markers such as PWV and CIMT in obese children and adolescents. This finding is important as obesity is a modifiable risk factor of cardiovascular disease (CVD), and exercise may help in reducing the future occurrence of CVD in this population.</p> 2020-05-01T00:00:00+02:00 Copyright (c) 2019 In vitro toxicity model: Upgrades to bridge the gap between preclinical and clinical research 2020-04-30T22:41:54+02:00 Eneko Madorran Andraž Stožer Sebastjan Bevc Uroš Maver <p>The Centers for Disease Control and Prevention (CDC) provides extensive data that indicate our need for drugs to maintain human population health. Despite the substantial availability of drugs on the market, many patients lack specific drugs. New drugs are required to tackle this issue. Moreover, we need more reliable models for testing drug toxicity, as too many drug approval failures occur with the current models. This article briefly describes various approaches of the currently used models for toxicity screening, to justify the selection of <em>in vitro</em> cell-based models. Cell-based toxicity models have the best potential to reliably predict drug toxicity in humans, as they are developed using the cells of the target organism. However, currently, a large gap exists between <em>in vitro</em> cell-based approach to toxicity testing and the clinical approach, which may be contributing to drug approval failures. We propose improvements to<em> in vitro</em> cell-based toxicity models, which is often an insight approach, to better match this approach with the clinical homeostatic approach. This should enable a more accurate comparison of data between the preclinical as well as clinical models and provide a more comprehensive understanding of human physiology and biological effects of drugs.</p> 2020-05-01T00:00:00+02:00 Copyright (c) 2019 The efficacy and safety of statin in combination with ezetimibe compared with double-dose statin in patients with high cardiovascular risk: A meta-analysis 2020-04-30T22:41:55+02:00 Yunyun Zhu Haochang Hu Jun Yang Qi Yao Hongyu Xu Yushan Yu Ting Liu Shaoyi Lin <p>Currently, statins are the first-line therapies for dyslipidemia and atherosclerotic cardiovascular disease, however, their hypolipidemic effects have not been satisfactory. We performed a meta-analysis to compare lipid-lowering efficacy and safety of ezetimibe and statin combination therapy with double-dose statin monotherapy in patients with high cardiovascular risk. Fourteen studies involving 3105 participants were included in the final analysis; 1558 (50.18%) participants received ezetimibe and statin combination therapy and 1547 (49.82%) received double-dose statin monotherapy. Eight studies reported the percentages of changes in several lipid parameters from baseline to endpoint in both groups. Lipid parameters changed more significantly in patients coadministered with ezetimibe and statin (low-density lipoprotein cholesterol [LDL-C]: MD = -9.39, 95% CI -13.36 to -5.42; non-high-density lipoprotein cholesterol [non-HDL-C]: MD = -10.36, 95% CI -14.23 to -6.50; total cholesterol [TC]: MD = -8.11, 95% CI -10.95 to -5.26; and triglyceride [TG]: MD = -5.96, 95% CI -9.12 to -2.80), with moderate to high heterogeneity among the studies. Two out of fourteen studies investigated several different statins. Our subgroup analysis showed that, compared with double-dose atorvastatin monotherapy, ezetimibe and atorvastatin combination therapy significantly decreased LDL-C, non-HDL-C, TC, and TG levels by 14.16%, 14.01%, 11.06%, and 5.96%, respectively (<em>p </em>&lt; 0.001). No significant difference was found in the incidence of laboratory-related adverse events (AEs) between statin combination therapy and monotherapy. Overall, ezetimibe and statin combination therapy significantly decreased LDL-C, non-HDL-C, and TC levels in patients with high cardiovascular risk, among which ezetimibe combined with atorvastatin had the best therapeutic effect. Compared with ezetimibe and statin combination therapy, double-dose statin monotherapy did not increase the risk of AEs.</p> 2020-05-01T00:00:00+02:00 Copyright (c) 2019