https://bjbms.org/ojs/index.php/bjbms/issue/feed BJBMS 2019-11-19T15:50:06+01:00 Faruk Skenderi faruk.skenderi@bjbms.org 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> https://bjbms.org/ojs/index.php/bjbms/article/view/4408 MALAT1 inhibits the Wnt/β-catenin signaling pathway in colon cancer cells and affects cell proliferation and apoptosis 2019-11-19T15:48:58+01:00 Junjun Zhang zaif5811@163.com Qian Li zaip6544@163.com Bing Xue yu062841@163.com Rui He zhai8407@163.com <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> 2019-11-15T13:06:41+01:00 Copyright (c) 2019 AMBSFBIH https://bjbms.org/ojs/index.php/bjbms/article/view/4434 Inhibition of miR-9 decreases osteosarcoma cell proliferation 2019-11-19T15:49:20+01:00 Wu Gang 24665088@qq.com Wei Tanjun 48817385@qq.com Huang Yong 1187321355@qq.com Qin Jiajun 22453547@qq.com Zhang Yi feiyi030@126.com Hu Hao 12914219@qq.com <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. Small interfering RNA against miR-9 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 knockdown in the human OS cell lines inhibits their metastatic potential, as determined by decreased cell proliferation and cell cycle arrest, decreased invasion, and increased apoptosis. The western blot analysis showed that cadherin-1 (CDH1), matrix metalloproteinase 13 (MMP-13), forkhead box O3 (FOXO3a), Bcl-2-like protein 11 (BCL2L11), and β-catenin (CTNNB1) 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> 2019-11-14T10:52:05+01:00 Copyright (c) 2019 ABMSFBIH https://bjbms.org/ojs/index.php/bjbms/article/view/4445 Prognostic role of NLR, PLR, and LMR in patients with pulmonary embolism 2019-11-19T15:49:43+01:00 Nuri Köse drnurikose@hotmail.com Tarık Yıldırım kdrtarik@gmail.com Fatih Akın fatih._akin@hotmail.com Seda Elçim Yıldırım sedaelcimdurusoy@gmail.com İbrahim Altun ibrahim_altun@yahoo.com <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. Control group consisted of 102 patients selected from outpatient clinics other than cardiology, cardiovascular surgery, and chest diseases. 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> 2019-11-13T08:56:51+01:00 Copyright (c) 2019 ABMSFBIH https://bjbms.org/ojs/index.php/bjbms/article/view/3560 p16/Ki-67 dual staining has a better accuracy than human papillomavirus (HPV) testing in women with abnormal cytology under 30 years old 2019-11-08T23:37:02+01:00 Laurențiu Pirtea laurentiupirtea@gmail.com Cristina Secosan cristina.secosan@gmail.com Madalin Margan marganmm@gmail.com Lavinia Moleriu laviniamoleriu@umft.ro Oana Balint oana.balint@gmail.com Dorin Grigoras grigorasdorin@ymail.com Ioan Sas sasioan56@yahoo.com Florin Horhat horhatflorin@yahoo.com Adelina Jianu adelina.jianu@gmail.com Răzvan Ilina razvanilina@yahoo.co.uk <p>Due to a high rate of transient human papillomavirus (HPV) infection, HPV genotyping has a low specificity for high-grade cervical lesions, especially in young women. p16/Ki-67 dual immunocytochemical staining can also be used for the detection of oncogenic changes in cervical cells. Our aim was to compare the performance of p16/Ki-67 dual staining and HPV genotyping in the detection of high-grade cervical lesions in patients with atypical squamous cells of undetermined significance (ASCUS)/low-grade squamous intraepithelial lesion (LSIL) on Pap smear. We retrospectively analyzed 310 patients with ASCUS/LSIL on Pap smear, who underwent colposcopy. Among these, 161 patients with suspected lesions detected by colposcopy were referred for biopsy. HPV genotyping by LINEAR ARRAY HPV Genotyping Test (CE-IVD) and p16/Ki-67 dual staining by CINtec PLUS Cytology kit was performed prior to cervical biopsy. The overall sensitivity and specificity of HPV genotyping for the detection of cervical intraepithelial neoplasia (CIN) 2-3 was 79% and 72%, respectively in patients with ASCUS, and 85% and 64%, respectively in patients with LSIL. For p16/Ki-67 test, sensitivity and specificity rate was 66% and 93%, respectively in ASCUS and 59% and 79%, respectively in LSIL group. The specificity of p16/Ki-67 staining was significantly higher in both groups in patients aged &lt;30 years compared to patients &gt;30 years old (<em>p</em> &lt; 0.001). Our results showed that p16/Ki-67 dual staining has a higher specificity compared to HPV genotyping, especially in patients under 30 years old. This indicates the usefulness of p16/Ki-67 testing in the triage of patients with ASCUS/LSIL and &lt;30 years old, prior to referral for colposcopy and biopsy.</p> 2019-11-08T00:00:00+01:00 Copyright (c) 2019 Association of Basic Medical Sciences https://bjbms.org/ojs/index.php/bjbms/article/view/4181 Effects of TCF7L2 rs7903146 variant on metformin response in patients with type 2 diabetes 2019-11-08T23:37:03+01:00 Tanja Dujic tanja.dujic@ffsa.unsa.ba Tamer Bego tamer.bego@ffsa.unsa.ba Maja Malenica maja.malenica@ffsa.unsa.ba Zelija Velija-Asimi zelijav@gmail.com Emma Ahlqvist emma.ahlqvist@med.lu.se Leif Groop leif.groop@med.lu.se Ewan R. Pearson E.Z.Pearson@dundee.ac.uk Adlija Causevic adlija.causevic@ffsa.unsa.ba Sabina Semiz ssemiz@ius.edu.ba <p>The response to metformin, the most commonly used drug for the treatment of type 2 diabetes (T2D), is highly variable. The common variant rs7903146 C&gt;T within the transcription factor 7-like 2 gene (<em>TCF7L2</em>) is the strongest genetic risk factor associated with T2D to date. In this study, we explored the effects of the <em>TCF7L2</em> rs7903146 genotype on metformin response in T2D. The study included 86 newly diagnosed patients with T2D, incident users of metformin. Levels of fasting glucose, insulin, HbA<sub>1c</sub>, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and anthropometric parameters were measured prior to metformin therapy, and 6 and 12 months after the treatment. Genotyping of the <em>TCF7L2</em> rs7903146 was performed by the Sequenom MassARRAY<span class="st"><sup>®</sup></span> iPLEX<span class="st"><sup>®</sup></span> platform. At baseline, the diabetes risk allele (T) showed an association with lower triglyceride levels (<em>p</em> = 0.037). After 12 months of metformin treatment, the T allele was associated with 25.9% lower fasting insulin levels (95% CI 10.9–38.3%, <em>p</em> = 0.002) and 29.1% lower HOMA-IR index (95% CI 10.1–44.1%, <em>p</em> = 0.005), after adjustment for baseline values. Moreover, the T allele was associated with 6.7% lower fasting glucose levels (95% CI 1.1–12.0%, <em>p</em> = 0.021), adjusted for baseline glucose and baseline HOMA-%B levels, after 6 months of metformin treatment. This effect was more pronounced in the TT carriers who had 16.8% lower fasting glucose levels (95% CI 7.0–25.6%,<em> p</em> = 0.002) compared to the patients with CC genotype. Our results suggest that the <em>TCF7L2</em> rs7903146 variant affects markers of insulin resistance and glycemic response to metformin in newly diagnosed patients with T2D within the first year of metformin treatment.</p> 2019-11-08T00:00:00+01:00 Copyright (c) 2019 Association of Basic Medical Sciences https://bjbms.org/ojs/index.php/bjbms/article/view/4213 Characteristics and prognostic factors of age-stratified high-grade intracranial glioma patients: A population-based analysis 2019-11-08T23:37:03+01:00 Yun Sun sunyunsy06@163.com Zhi-Yong Xiong xiongzy15@126.com Peng-Fei Yan yanpengfeipf@163.com Liang-Lei Jiang jianglianglei08@163.com Chuan-Sheng Nie chuanshengnn16@yeah.net Xuan Wang highprefer@126.com <p>We evaluated characteristics and different prognostic factors for survival in age-stratified high-grade glioma in a U.S. cohort. Eligible patients were identified in the Surveillance, Epidemiology, and End Results (SEER) registries and stratified into 3 age groups: 20–39 years old (1,043 patients), 40–59 years old (4,503 patients), and <u>&gt;</u>60 years old (5,045 patients). Overall and cancer-related survival data were obtained. Cox models were built to analyze the outcomes and risk factors. It showed that race was a prognostic factor for survival in patients 40 to 59 years old and in patients ≥60 years old. Partial resection was associated with lower overall survival and cause-specific survival in all age groups (overall survival: 20–39 yr: HR = 6.41; 40–59 yr: HR = 4.84; <u>&gt;</u>60 yr: HR = 5.06; cause-specific survival: 20–39 yr: HR = 5.87; 40–59 yr: HR = 4.01; <u>&gt;</u>60 yr: HR = 3.36). The study highlights that, while some prognostic factors are universal, others are age-dependent. The effectiveness of treatment approaches differs for patients in different age groups. Results of this study may help to develop personalized treatment protocols for glioma patients of different ages.</p> 2019-11-08T00:00:00+01:00 Copyright (c) 2019 Association of Basic Medical Sciences https://bjbms.org/ojs/index.php/bjbms/article/view/4332 Postoperative pulmonary complications in contemporary cohort of patients with pulmonary hypertension 2019-11-08T23:37:03+01:00 S. Chandralekha Kruthiventi Kruthiventi.Chandralekha@gmail.com Garvan C. Kane kane.garvan@mayo.edu Juraj Sprung sprung.juraj@mayo.edu Toby N. Weingarten weingarten.toby@mayo.edu Mary Ellen Warner warner.mary@mayo.edu <p>Patients with pulmonary hypertension are at increased risk for postoperative pulmonary complications (PPCs). Herein, we review PPCs in pulmonary hypertension patients undergoing non-cardiac procedures under general anesthesia. The medical records of pulmonary hypertension patients who underwent surgery with general anesthesia between 2010 and 2017 were reviewed for PPCs. In addition we reviewed nursing-documented respiratory depressive episodes in the post-anesthesia care unit to assess the associations between these episodes and later PPCs. There were 20 PPCs among 128 patients who underwent 197 procedures (10.2 per 100 surgeries) [95% CI 6.7–15.2]. Of these, 5 occurred during anesthesia recovery and 15 following anesthesia recovery. Three-quarters of the PPCs occurred within 24 postoperative hours. All the PPCs were severe. The frequency of PPCs was significantly higher in those who experienced respiratory depression during anesthesia recovery vs. in those who did not (5/17, 29% vs. 10/175, 6%; odds ratio 5.15, 95% CI 1.58–16.81, <em>p</em> = 0.007). Increased PPC rates were observed among patients who were current/previous smokers and who routinely use benzodiazepines, and among those undergoing emergent surgery. With treatment, all PPCs resolved. The rate of PPCs in the population of contemporary surgical pulmonary hypertension patients was 10.2%, and three-quarters occurred during first 24 postoperative hours. Patients who had respiratory depression during anesthesia recovery were 5-fold more likely to experience later PPCs.</p> 2019-11-08T00:00:00+01:00 Copyright (c) 2019 Association of Basic Medical Sciences https://bjbms.org/ojs/index.php/bjbms/article/view/4136 Recombinant deoxyribonucleoside kinase from Drosophila melanogaster can improve gemcitabine based combined gene/chemotherapy for targeting cancer cells 2019-11-08T23:37:02+01:00 Mahak Fatima mehakdar@hotmail.co.uk Muhammad Mubashar Iqbal Ahmed mubashar143all@yahoo.com Faiza Batool faizabatool09@gmail.com Anjum Riaz anjum.ibb@pu.edu.pk Moazzam Ali moazzam@ibb.pu.edu.pk Birgitte Munch-Petersen bmp@ruc.dk Zeeshan Mutahir zeeshan.ibb@pu.edu.pk <p>A recombinant deoxyribonucleoside kinase from <em>Drosophila melanogaster</em> with a deletion of the last 20 amino acid residues (named <em>Dm</em>dNKΔC20) was hypothesized as a potential therapeutic tool for gene therapy due to its broad substrate specificity and better catalytic efficiency towards nucleosides and nucleoside analogs. This study was designed to evaluate the effect of <em>Dm</em>dNKΔC20 for sensitizing human cancer cell lines to gemcitabine and to further investigate its role in reversal of acquired drug resistance in gemcitabine-resistant cancer cell line. The <em>DmdNKΔC20</em> gene was delivered to three different cancer cell lines, including breast, colon and liver cancer cells, using lipid-mediated transfection reagent. After transfection, gene expression of <em>DmdNKΔC20 </em>was confirmed by quantitative reverse transcription PCR (qRT-PCR) and the combined effect of <em>Dm</em>dNKΔC20 and gemcitabine based cytotoxicity was observed by cell viability assay. We further evolved a gemcitabine-resistant breast cancer cell line (named MCF7-R) through directed evolution in the laboratory, which showed 375-fold more resistance compared with parental MCF7 cells. Upon transfection with <em>DmdNKΔC20</em> gene, MCF7-R cells showed 83-fold higher sensitivity to gemcitabine compared with the control group of MCF7-R cells. Moreover, we observed 79% higher expression of p21 protein in transfected MCF7-R cells, which may indicate induction of apoptosis. Our findings highlight the importance and therapeutic potential of <em>DmdNKΔC20 </em>in combined gene/chemotherapy approach to target a wide range of cancers<em>,</em> particularly gemcitabine-resistant cancers.</p> 2019-11-08T00:00:00+01:00 Copyright (c) 2019 Association of Basic Medical Sciences https://bjbms.org/ojs/index.php/bjbms/article/view/4227 Role of FBXW7 in the quiescence of gefitinib-resistant lung cancer stem cells in EGFR-mutant non-small cell lung cancer 2019-11-08T23:37:03+01:00 Moulid Hidayat moulid@juntendo.ac.jp Yoichiro Mitsuishi y-mitsuishi@juntendo.ac.jp Fumiyuki Takahashi tfjtakaha@juntendo.ac.jp Ken Tajima tajiken@juntendo.ac.jp Toshifumi Yae tyae@juntendo.ac.jp Katsumi Miyahara katsuo@juntendo.ac.jp Daisuke Hayakawa dhayaka@juntendo.ac.jp Wira Winardi w-winardi@juntendo.ac.jp Hiroaki Ihara h-ihara@juntendo.ac.jp Yoshika Koinuma ymatsuda@juntendo.ac.jp Aditya Wirawan aditya@juntendo.ac.jp Fariz Nurwidya fariz.nurwidya@gmail.com Motoyasu Kato mtkatou@juntendo.ac.jp Isao Kobayashi isao-k@juntendo.ac.jp Shinichi Sasaki ssasaki@juntendo-urayasu.jp Kazuya Takamochi ktakamo@juntendo.ac.jp Takuo Hayashi tkhyz@juntendo.ac.jp Yoshiyuki Suehara ysuehara@juntendo.ac.jp Mariko Moriyama mariko@phar.kindai.ac.jp Hiroyuki Moriyama moriyama@phar.kindai.ac.jp Sonoko Habu sonoko-h@juntendo.ac.jp Kazuhisa Takahashi kztakaha@juntendo.ac.jp <p>Several recent studies suggest that cancer stem cells (CSCs) are involved in intrinsic resistance to cancer treatment. Maintenance of quiescence is crucial for establishing resistance of CSCs to cancer therapeutics. F-box/WD repeat-containing protein 7 (FBXW7) is a ubiquitin ligase that regulates quiescence by targeting the c-MYC protein for ubiquitination. We previously reported that gefitinib-resistant persisters (GRPs) in <em>EGFR</em>-mutant non-small cell lung cancer (NSCLC) cells highly expressed octamer-binding transcription factor 4 (Oct-4) as well as the lung CSC marker CD133, and they exhibited distinctive features of the CSC phenotype. However, the role of FBXW7 in lung CSCs and their resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors in NSCLC is not fully understood. In this study, we developed GRPs from the two NSCLC cell lines PC9 and HCC827, which express an <em>EGFR</em> exon 19 deletion mutation, by treatment with a high concentration of gefitinib. The GRPs from both PC9 and HCC827 cells expressed high levels of CD133 and FBXW7, but low levels of c-MYC. Cell cycle analysis demonstrated that the majority of GRPs existed in the G0/G1 phase. Knockdown of the <em>FBXW7</em> gene significantly reduced the cell number of CD133-positive GRPs and reversed the cell population in the G0/G1-phase. We also found that FBXW7 expression in CD133-positive cells was increased and c-MYC expression was decreased in gefitinib-resistant tumors of PC9 cells in mice and in 9 out of 14 tumor specimens from <em>EGFR</em>-mutant NSCLC patients with acquired resistance to gefitinib. These findings suggest that FBXW7 plays a pivotal role in the maintenance of quiescence in gefitinib-resistant lung CSCs in <em>EGFR </em>mutation-positive NSCLC.</p> 2019-11-08T00:00:00+01:00 Copyright (c) 2019 Association of Basic Medical Sciences https://bjbms.org/ojs/index.php/bjbms/article/view/4002 Association of serum chemerin and inflammatory factors with type 2 diabetes macroangiopathy and waist-to-stature ratio 2019-11-08T23:37:02+01:00 Mengxue Yang yangmengx123@163.com Xue Zhou 692375203@qq.com Jie Xu 649904039@qq.com Bo Yang ybsurge@qq.com Jie Yu 18275615519@163.com Qihai Gong ysgong@126.com Xuan Zhang 690566160@qq.com Xiaohua Sun Nbsunxh@126.com Qun Zhang 1481805012@qq.com Jinying Xia xiajinying8901@126.com Jianhui Li lijianhuinb@163.com <p>Chemerin is an adipocytokine that participates in glycolipid metabolism; however, its association with type 2 diabetes (T2DM) with lower extremity macroangiopathy (T2DM-V) has rarely been reported. This study explored the association of chemerin and inflammatory factors with body fat parameters, glucolipid metabolism, and insulin resistance (IR) in T2DM and T2DM-V. Patients were classified into normal glucose regulation (NGR), T2DM, and T2DM-V groups. Serum chemerin, glucolipid metabolic parameters, transforming growth factor (TGF)-β, interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, and fasting insulin levels were measured along with HOMA-IR, body mass index (BMI), and waist-to-stature ratio (WSR). Serum chemerin, TGF-β, IL-6, and MCP-1 levels were significantly higher in T2DM groups than in NGR group, and BMI, WSR, fasting plasma glucose (FPG), 2hPG, glycated hemoglobin (HbA1c), triglycerides (TG), and HOMA-IR were higher in T2DM-V subgroups with moderate or severe lower extremity macroangiopathy than in NGR group, simple T2DM group, and T2DM-V subgroup with mild macroangiopathy. FPG, 2hPG, HbA1c, TG, and HOMA-IR were higher in T2DM-V subgroup with severe macroangiopathy than in T2DM-V with moderate macroangiopathy (<em>p</em> &lt; 0.05). In all groups, serum chemerin levels were positively correlated with BMI, WSR, FPG, 2hPG, HbA1c, fasting insulin, aspartate transaminase, TG, TGF-β, IL-6, and HOMA-IR (<em>p </em>&lt; 0.05) and negatively correlated with high-density lipoprotein cholesterol [HDL-c] (<em>p</em> &lt; 0.05). Multiple stepwise regression analysis showed that 2hPG, HbA1c, and HDL-c were independent predictors of serum chemerin levels (β = -0.768, -0.122, -0.115, and 3.261, respectively; <em>p</em> &lt; 0.01). Collectively, chemerin, factors associated with obesity, pathological and physiological changes in glucolipid metabolism, and inflammatory factors may promote the development of T2DM macroangiopathy.</p> 2019-11-08T00:00:00+01:00 Copyright (c) 2019 Association of Basic Medical Sciences https://bjbms.org/ojs/index.php/bjbms/article/view/3977 Adjunct corticosteroid treatment in patients with pneumonia: A precision medicine approach 2019-11-08T23:37:02+01:00 Srdjan Gavrilovic srdjan.gavrilovic@mf.uns.ac.rs Ana Andrijevic ana.andrijevic@yahoo.com Aida Mujakovic mujakovic.aida@gmail.com Yewande Odeyemi odeyemi.yewande@mayo.edu Belma Paralija paralijabelma@gmail.com Ognjen Gajic Gajic.ognjen@mayo.edu <p>Pneumonia is the leading infectious cause of death worldwide. While inflammation is critically important in host response to microbial invasion, exaggerated inflammation can damage the lungs, contributing to respiratory failure and mortality. Corticosteroids are effective in reducing inflammation and can also cause immune suppression. Presently, clinicians are unable to reliably distinguish between exaggerated and appropriate immune response and thus cannot rapidly identify patients most likely to benefit from adjunctive corticosteroids. In this review, we propose a biomarker-guided, precision medicine approach to corticosteroid treatment, aimed to give these medications at appropriate dose and time and only to patients who have exaggerated inflammation.</p> 2019-11-08T00:00:00+01:00 Copyright (c) 2019 Association of Basic Medical Sciences https://bjbms.org/ojs/index.php/bjbms/article/view/4114 Optogenetics: Therapeutic spark in neuropathic pain 2019-11-08T23:37:02+01:00 Kang Liu liuk997@126.com Long Wang wanglongwhu@163.com <p>Optogenetics is an emerging field, which uses light and molecular genetics to manipulate the activity of live cells by expressing light-sensitive proteins. With the discovery of bacteriorhodopsin, a light-sensitive bacterial protein, in 1971 Oesterhelt and Stoeckenius laid the pavement of optogenetics. However, the cross-integration of different disciplines is a little more than a decade old. The toolbox contains fluorescent sensors and optogenetic actuators that enable visualization of signaling events and manipulation of cellular activities, respectively. Neuropathic pain is pain caused either by damage or disease that affects the somatosensory system. The exact mechanism for neuropathic pain is not known, however proposed mechanisms include immune reactions, ion channel expressions, and inflammation. Current regimen for the disease provides about 50% relief for only 40–60% of patients. Recent <em>in vivo</em> and <em>in vitro</em> studies demonstrate the potential therapeutic applications of optogenetics by manipulating the activity of neurons. This review summarizes the basic concept, therapeutic applications for neuropathy, and potential of optogenetics to reach from bench to bedside in the near future.</p> 2019-11-08T00:00:00+01:00 Copyright (c) 2019 Association of Basic Medical Sciences https://bjbms.org/ojs/index.php/bjbms/article/view/4182 Clear cell urothelial carcinoma of the urinary bladder - a rare pathological entity. A case report and a systematic review of the literature 2019-11-08T23:37:03+01:00 Ioana Mihai joana.mihai@yahoo.com Sorina Taban sorinataban@yahoo.com Alin Cumpanas alincumpanas@hotmail.com Emilian Gh. Olteanu olteanugheorgheemilian@gmail.com Mihaela Iacob iacobmiha@yahoo.com Alis Dema dema_alis@yahoo.com <p>The most common histological type of urinary bladder cancer is urothelial carcinoma (UC). In contrast, the clear cell variant of urothelial carcinoma (CCUC) is quite a rare neoplasm. In this study, we report a case of an 81-year-old male, presenting with gross hematuria and acute urinary retention, which was subsequently diagnosed with CCUC at our pathology department. Furthermore, we provide a short systematic review of the literature (PubMed, Scopus, and Science Citation Index) for this rare histopathological entity and a brief discussion about its morphological and immunohistochemical (IHC) characteristics.</p> 2019-11-08T00:00:00+01:00 Copyright (c) 2019 Association of Basic Medical Sciences https://bjbms.org/ojs/index.php/bjbms/article/view/4349 Making sense of subclinical cardiac alterations in patients with diabetes 2019-11-08T23:37:02+01:00 Manan Pareek mananpareek@dadlnet.dk Michael Hecht Olsen michael.olsen@dadlnet.dk <p>Patients with diabetes are prone to develop a distinct primary myocardial condition, diabetic cardiomyopathy, placing them at an increased risk for heart failure [1-3]. This occurs independently of hypertension, coronary artery disease, and other established causes of heart failure. Pertinent findings include increased mass, concentric changes, and diastolic dysfunction of the left ventricle [4,5]. Such adverse remodeling is common among patients with diabetes and appears to be strongly associated with its duration, suggesting a role for persistent metabolic stress [6-8]. However, which exact components of the diabetic syndrome determine these cardiac alterations is not clear. Moreover, most studies have investigated patients with type 2 diabetes, and it is uncertain whether patients with type 1 diabetes experience similar myocardial changes.</p> <p><em>Continue reading the full text in the <strong><a href="https://bjbms.org/ojs/index.php/bjbms/article/view/4349/1240">PDF</a></strong> version.</em></p> 2019-11-08T00:00:00+01:00 Copyright (c) 2019 Association of Basic Medical Sciences https://bjbms.org/ojs/index.php/bjbms/article/view/4437 The efficacy and safety of statin in combination with ezetimibe compared with double-dose statin in patients with high cardiovascular risk: A meta-analysis 2019-11-04T15:04:31+01:00 Yunyun Zhu zhu_yy0122@126.com Haochang Hu huhaochang@163.com Jun Yang yangjun4499@163.com Qi Yao nbyaoqi@sina.com Hongyu Xu jjxhy405@163.com Yushan Yu 24087594@qq.com Ting Liu ltblue927@126.com Shaoyi Lin shaoyi_lin@hotmail.com <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 3,105 participants were included in the final analysis; 1,558 (50.18%) participants received ezetimibe and statin combination therapy and 1,547 (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 co-administered 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> 2019-10-31T09:26:03+01:00 Copyright (c) 2019 Bosnian Journal of Basic Medical Sciences https://bjbms.org/ojs/index.php/bjbms/article/view/4410 Dihydromyricetin promotes autophagy and attenuates renal interstitial fibrosis by regulating miR-155-5p/PTEN signaling in diabetic nephropathy 2019-10-31T15:44:59+01:00 Liming Guo LimingGuosdf@163.com Kuibi Tan KuibiTandrt@163.com Qun Luo QunLuower@163.com Xu Bai XuBaiert@163.com <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&nbsp;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&nbsp;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> 2019-10-31T00:00:00+01:00 Copyright (c) 2019 Bosnian Journal of Basic Medical Sciences https://bjbms.org/ojs/index.php/bjbms/article/view/4391 The effects of mutational profiles on phenotypic presentation of myeloproliferative neoplasm subtypes in Bosnia: 18 year follow-up 2019-11-01T16:17:29+01:00 Amina Kurtovic-Kozaric amina.kurtovic@gmail.com Erna Islamagic erna.islamagic@hotmail.com Hana Komic hana.komic_1993@hotmail.com Nurija Bilalovic nurija62@gmail.com Izet Eminovic eminovicizet@gmail.com Adnan Burekovic adnan.burekovic@gmail.com Amna Uzunovic amna.uzunovic@gmail.com Sabira Kurtovic sabira.kurtovic@gmail.com <p>The identification of mutually exclusive somatic mutations shared among myeloproliferative neoplasm (MPN) subtypes&nbsp;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, and mutational status of the <em>JAK2</em>, <em>CALR</em>, and <em>MPL</em> genes. We compared hematologic and clinical features of <em>JAK2</em><sup>V617F</sup>-ET vs.&nbsp;<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> 2019-10-30T11:02:50+01:00 Copyright (c) 2019 Bosnian Journal of Basic Medical Sciences https://bjbms.org/ojs/index.php/bjbms/article/view/4216 Inhibitory effect of microRNA-608 on lung cancer cell proliferation, migration, and invasion by targeting BRD4 through the JAK2/STAT3 pathway 2019-10-17T15:41:16+02:00 Weigang Xu 359330683@qq.com Dapeng Sun yitianlong2@126.com Yanqin Wang 15863100539@163.com Xinlin Zheng zxlxinlin@163.com Yan Li xiangyanlu0421@126.com Yu Xia xiayujiejie12@163.com Ya'nan Teng tengyanan502@aliyun.com <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> 2019-10-17T10:47:26+02:00 Copyright (c) 2019 Bosnian Journal of Basic Medical Sciences https://bjbms.org/ojs/index.php/bjbms/article/view/4378 In vitro toxicity model: Upgrades to bridge the gap between preclinical and clinical research 2019-10-16T15:40:57+02:00 Eneko Madorran eneko.madorran@um.si Andraž Stožer andraz.stozer@um.si Sebastjan Bevc Sebastjan.BEVC@ukc-mb.si Uroš Maver uros.maver@um.si <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> 2019-10-16T09:56:56+02:00 Copyright (c) 2019 Bosnian Journal of Basic Medical Sciences https://bjbms.org/ojs/index.php/bjbms/article/view/4409 Inflammatory cells in perivascular adipose tissue and the integrity of the tunica media in atherosclerotic coronary arteries 2019-11-19T15:50:06+01:00 Ruda Zorc-Pleskovič Ruda.Zorc-Pleskovic@mf.uni-lj.si Marjeta Zorc Marjeta.Zorc@mf.uni-lj.si Dušan Šuput Dusan.Suput@mf.uni-lj.si Aleksandra Milutinović sandramilutinovic@yahoo.com <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> 2019-09-27T01:31:08+02:00 Copyright (c) 2019 Bosnian Journal of Basic Medical Sciences