Bosnian Journal of Basic Medical Sciences <p>The BJBMS (Bosnian Journal of Basic Medical Sciences) is а premier venue for discoveries in basic and clinical biomedical science. The BJBMS was founded in 1998 and is published by the Association of Basic Medical Sciences, a nonprofit honor organization of physician-scientists.</p> <p>Broad readership and scope. The BJBMS reaches readers across a wide range of medical disciplines and sectors. The journal publishes basic and translational/clinical research submissions and reviews in all biomedical specialties, including Genetics and Molecular biology, Immunology, Microbiology, Pathology, Biochemistry, Pharmacology, Anatomy, Biomaterials, new and emerging research and diagnostic methods, new and emerging medical entities, and others.</p> en-US (Faruk Skenderi) (Armin Sehovic) Mon, 02 Nov 2020 00:00:00 +0100 OJS 60 Accelerated atherosclerosis in premenopausal women with rheumatoid arthritis – 15-year follow-up <p>Rheumatoid arthritis (RA) is a chronic inflammatory disease, associated with increased mortality and morbidity due to the higher cardiovascular risk in these patients. Traditional risk factors are not the only answer for the accelerated atherosclerosis. In long term prospective study, we investigated the relationship between asymptomatic atherosclerosis and traditional risk factors as well as inflammatory markers in patients with RA and matched healthy controls. We studied the laboratory test results, the concentrations of inflammatory mediators, matrix metalloproteases (MMP) and inflammation markers in the total of 70 (60 at follow-up) premenopausal healthy women with RA and 40 (34 at follow-up) matched controls’. We used the B-mode ultrasound imaging of carotid arteries for detection of asymptomatic atherosclerosis. Correlation with different factors was evaluated. Statistically significant higher values of inflammatory markers such as selective adhesion molecules ICAM &amp; VCAM, interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and MMP-3 in patients` group were found in the follow-up study. More plaques were found in the patients’ group (42.4% vs. 12.9%; <em>p</em>=0.005), as compared with the controls’ group. The patients had also higher values of cIMT (<em>p</em>=0.001). Using bivariate regression analysis only VCAM was found as a prognostic factor for plaque occurrence (r= 0. 341, <em>p</em>=0.016), but not for cIMT (r= -0.130, <em>p</em>=0.327) in premenopausal female patients with RA after the follow-up. Therefore, the asymptomatic atherosclerosis is accelerated in premenopausal women with RA. The results of our follow-up study showed the association between the inflammation and accelerated atherosclerosis. Furthermore, VCAM was found to have statistically significant correlation with plaque occurrence in these patients.</p> Metka Koren Krajnc, Radovan Hojs, Iztok Holc, Željko Knez, Artur Pahor Copyright (c) 2020 Metka Koren Krajnc, Radovan Hojs, Iztok Holc, Željko Knez, Artur Pahor Wed, 25 Nov 2020 00:29:35 +0100 Stomach-specific c-Myc overexpression drives gastric adenoma in mice via AKT/mTOR signaling <p>Gastric cancer (GC) is one of the most common malignant cancers in the world.<em> c-Myc</em>, a well-known oncogene, is commonly amplified in many cancers, including gastric cancer. However, it is still not completely understood how<em> c-Myc</em> functions in GC. Here, we generated a stomach-specific <em>c-Myc</em> transgenic mouse model to investigate its role in GC. We found that overexpression of <em>c-Myc </em>in <em>Atp4b<sup>+</sup></em> gastric parietal cells could induce gastric adenoma in mice. Mechanistically, <em>c-Myc</em> promoted tumorigenesis via the AKT/mTOR pathway. Furthermore, AKT inhibitor (MK-2206) or mTOR inhibitor (Rapamycin) inhibited the proliferation of <em>c-Myc</em> overexpressing gastric cancer cell lines. Thus, our findings highlight that gastric tumorigenesis can be induced by <em>c-Myc</em> overexpression through activation of the AKT/mTOR pathway.</p> Jing Liu, Wenxin Feng, Min Liu, Hanyu Rao, Xiaoxue Li, Yan Teng, Xiao Yang, Jin Xu, Weiqiang Gao, Li Li Copyright (c) 2020 Jing Liu, Wenxin Feng, Min Liu, Hanyu Rao, Xiaoxue Li, Yan Teng, Xiao Yang, Jin Xu, Weiqiang Gao, Li Li Thu, 19 Nov 2020 23:45:46 +0100 Raloxifene inhibits the overexpression of TGF-β1 in cartilage and regulates the metabolism of subchondral bone in rats with osteoporotic osteoarthritis <p>Overexpression of transforming growth factor-beta 1 (TGF-β1) and subchondral bone remodeling play key roles in osteoarthritis (OA). Raloxifene (RAL) reduces the serum level of TGF-β1 in postmenopausal women. However, the effect of RAL on TGF-β1 expression in articular cartilage remains unclear. Therefore, we aimed to investigate the protective effect of RAL against osteoporotic OA mediated by TGF-β1 expression in the cartilage and the metabolism of subchondral bone. Osteoporotic OA was induced by a combination of anterior cruciate ligament transection (ACLT) and ovariectomy (OVX). Rats were divided into five groups (n=12): the sham, ACLT, OVX, ACLT+OVX and RAL groups (ACLT+OVX+RAL, 6.25 mg/kg/day for 12 weeks). Assessment was performed by histomorphology, microcomputed tomography (micro-CT), immunohistochemistry and tartrate-resistant acid phosphatase (TRAP) staining. Extreme cartilage degeneration was detected in the ACLT+OVX group. The histomorphological scores, levels of TGF-β1 and its related catabolic enzymes and osteoclasts numbers in the ACLT+OVX group were higher than those in other groups (<em>p</em>&lt;0.05). Furthermore, the structure model index (SMI) and trabecular spacing (Tb.Sp) were decreased (<em>p</em>&lt;0.05), while the bone mineral density (BMD), bone volume fraction (BV/TV) and trabecular number (Tb.N) were increased after treatment with RAL compared with the corresponding parameters in the ACLT+OVX group (<em>p</em>&lt;0.05). Our findings demonstrated that RAL at clinical doses retards the development of osteoporotic OA associated with the inhibition of TGF-β1 overexpression in the cartilage and regulation of subchondral bone metabolism. These results suggest an expansion of the clinical indications for RAL to include the prevention and treatment of postmenopausal OA.</p> Shao-Hua Ping, Fa-Ming Tian, Hao Liu , Qi Sun, Li-Tao Shao, Qiang-Qiang Lian, Liu Zhang Copyright (c) 2020 Shao-Hua Ping, Fa-Ming Tian, Hao Liu , Qi Sun, Li-Tao Shao, Qiang-Qiang Lian, Liu Zhang Thu, 19 Nov 2020 00:49:50 +0100 A plea for extension of the anatomical nomenclature: Vessels <p>This article is the fourth and last part of a series aimed at extending and correcting the anatomical nomenclature. Because of the rapid development of internet and the use of electronic formats in communication in anatomy, embryology, histology, medical education and clinical medicine, an appropriate, precise and concise anatomical nomenclature is required. Such tool enables to avoid any potential confusion and possible scientific/medical mistakes. The up-to-date official anatomical terminology, Terminologia Anatomica, is available longer than 20 years and needs to be refined and extended. The authors have collected and listed 210 terms and completed them with definitions and/or explanations. We aimed to start a discussion about their potential incorporation into the new revised version of the Terminologia Anatomica. This article is primarily focused on the vessels of the human body (arteries, veins and lymphatic system).</p> David Kachlik, Vladimir Musil, Alzbeta Blankova , Zuzana Marvanova , Jakub Miletin, Daniela Trachtova , Vlasta Dvorakova , Vaclav Baca Copyright (c) 2020 David Kachlik, Vladimir Musil, Alzbeta Blankova , Zuzana Marvanova , Jakub Miletin, Daniela Trachtova , Vlasta Dvorakova , Vaclav Baca Tue, 17 Nov 2020 22:18:32 +0100 Bioinformatics analysis reveals TSPAN1 as a candidate biomarker of progression and prognosis in pancreatic cancer <p>Pancreatic cancer (PCC) is a common malignant tumor of the digestive system that is resistant to traditional treatments and has an overall 5-year survival rate of &lt;7%. Transcriptomics research provides reliable biomarkers for diagnosis, prognosis, and clinical precision treatment, as well as the identification of molecular targets for the development of drugs to improve patient survival. We sought to identify new biomarkers for PCC by combining transcriptomics and clinical data with current knowledge regarding molecular mechanisms. Consequently, we employed weighted gene co-expression network analysis and differentially expressed gene analysis to evaluate genes co-expressed in tumor versus normal tissues using pancreatic adenocarcinoma data from The Cancer Genome Atlas and dataset GSE16515 from the Gene Expression Omnibus. Twenty-one overlapping genes were identified, with enrichment of key Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways, including epidermal growth factor receptor signaling, cadherin, cell adhesion, ubiquinone, and glycosphingolipid biosynthesis pathways, and retinol metabolism. Protein-protein interaction analysis highlighted 10 hub genes, according to Maximal Clique Centrality. Univariate and multivariate COX analyses indicated that TSPAN1 serves as an independent prognostic factor for PCC patients. Survival analysis distinguished TSPAN1 as an independent prognostic factor among hub genes in PCC. Finally, immunohistochemical staining results suggested that the TSPAN1 protein levels in the Human Protein Atlas were significantly higher in tumor tissue than in normal tissue. Therefore, TSPAN1 may be involved in PCC development and act as a critical biomarker for diagnosing and predicting PCC patient survival.</p> Chenhui Ma, ZeLong Cui, YiChao Wang , Lei Zhang, JunYe Wen , HuaiBin Guo, Na Li, WanXing Zhang Copyright (c) 2020 Chenhui Ma, ZeLong Cui, YiChao Wang , Lei Zhang, JunYe Wen , HuaiBin Guo, Na Li, WanXing Zhang Sat, 14 Nov 2020 15:23:27 +0100 Epigenetically inactivated RASSF1A as a tumor biomarker <p><em>RASSF1A</em> represents one of the eight isoforms of the <em>RASSF1</em> gene. <em>RASSF1A</em> is a tumor suppressor gene whose inactivation influences tumor initiation and development. In cancer, <em>RASSF1A</em> is frequently inactivated by mutations, loss of heterozygosity and, most commonly, by promoter hypermethylation. As epigenetic inactivation of <em>RASSF1A</em> was detected in various cancer types, it was extensively investigated and nowadays, the research on <em>RASSF1A</em> promoter methylation proceeds in the light of an epigenetic tumor biomarker. Analyses of DNA methylation of genes involved in carcinogenesis such as<em> RASSF1A</em> are currently done mostly on genomic DNA (gDNA). Simultaneously, cell-free DNA (cfDNA) from liquid biopsies has lately been developed as an early cancer diagnostic tool.&nbsp; This review discusses the evidence on aberrantly methylated <em>RASSF1A</em> in gDNA and cfDNA from different cancer types and its utility for early cancer diagnosis, prognosis, and surveillance. Furthermore, methylation frequencies of <em>RASSF1A</em> in gDNA and cfDNA were compared in various cancer types. The weaknesses and strengths of the investigations mentioned above are discussed. In conclusion, although the importance of <em>RASSSF1A</em> methylation in relation to cancer was established, and it became included in several diagnostic panels, the evidence of its diagnostic utility is still experimental and not yet implemented in standard clinical health care.</p> Dora Raos, Monika Ulamec, Ana Katusic Bojanac, Floriana Bulic-Jakus, Davor Jezek, Nino Sincic Copyright (c) 2020 Dora Raos, Monika Ulamec, Ana Katusic Bojanac, Floriana Bulic-Jakus, Davor Jezek, Nino Sincic Wed, 11 Nov 2020 21:50:06 +0100 Can NLR, PLR and LMR be used as prognostic indicators in patients with pulmonary embolism? Author’s reply on commentary <p>We appreciate the comments made by Dr Bedel and colleagues. NLR, PLR and LMR are affected by various diseases such as oncological, collagen tissue, inflammatory, or severe renal/liver diseases [1]. Because of this, we have listed some of the above-mentioned disorders in the tables. Hematological diseases, collagen tissue disease, inflammatory diseases, congenital heart disease, or severe renal/liver disease were therefore excluded from the study. However, the presence of malignancy did not affect our results in regression analysis.<br>Platelets swell until 120 minutes in ethylene diamine tetra acetic (EDTA) and until 60 minutes in citrate [2]. Authors suggest that optimal measuring time should not exceed 120 minutes. The blood samples of the patients were taken within 1 hour after their emergency admission. All blood samples in our study were tested within 1 hour of collection [3]. We used EDTA for whole blood anticoagulation. The mean duration of symptoms prior to admission was 5.04 ± 6.9 days. <br>The drugs such as corticosteroids affect inflammatory parameters. Therefore, we excluded inflammatory diseases without emphasizing corticosteroids or other anti-inflammatory drugs.</p> Nuri Kose, Tarık Yıldırım, Fatih Akın, Seda Elçim Yıldırım, Ibrahim Altun Copyright (c) 2020 Nuri Kose, Tarık Yıldırım, Fatih Akın, Seda Elçim Yıldırım, Ibrahim Altun Fri, 06 Nov 2020 01:56:50 +0100 Can NLR, PLR and LMR be used as prognostic indicators in patients with pulmonary embolism? A commentary <p>We read with great interest the article “Prognostic role of NLR, PLR, and LMR in patients with pulmonary embolism” by Köse et al.[1]. They found that the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR) were related to the prognosis and clinical severity of patients with pulmonary embolism (PE). First of all, we congratulate the authors for their invaluable contribution to literature. However, we think that there are some points that should be discussed regarding the use of these laboratory parameters.</p> <p>White blood cell subtypes NLR, PLR, and LMR have been associated with many inflammatory diseases, including PE [2,3]. These parameters, which can be easily determined by simple and easy measurement of systemic inflammation, maintain their importance today. However, these parameters are affected by many factors such as trauma, local or systemic infection, acute coronary syndromes, and malignancy [3-5]. For these reasons, it would be better for the authors to mention these factors and exclude them from the tables that included malignancy and trauma patients in the study.</p> <p>It is known that drugs including steroids can increase neutrophils and decrease lymphocytes and therefore affect NLR, PLR and LMR values [6]. Therefore, it will be more valuable to exclude patients who use drugs that may affect laboratory parameters. In addition, plasma inflammatory biomarkers are time dependent variables, the time of sample collection and the time from the onset of the symptom to the sampling may have an impact on the parameters [3-6]. Therefore, it is important to identify the time from first symptom to sample collection and the factors that may affect it. In conclusion, because NLR, PLR and LMR can be affected by many factors, prospective studies with large populations are needed to show the accuracy of use in critically ill patients.</p> Cihan Bedel, Mustafa Korkut, Hamit Hakan Armağan Copyright (c) 2020 Cihan Bedel, Mustafa Korkut, Hamit Hakan Armağan Fri, 06 Nov 2020 01:34:17 +0100 Immunohistochemical study of dental pulp cells with 3D collagen type I gel in demineralized dentin tubules in vivo <p>Dental pulp cells (DPCs) represent good candidates for the regeneration of dental tissue. This study aimed to evaluate the growth and differentiation potential of DPCs cultured inside demineralized dentin tubules <em>in vivo</em>. Six green fluorescent protein-transgenic rats (body weight 100 g each) and thirty-two Sprague-Dawley (SD) male rats (body weight 250 g each) were used for DPC collection and dentin tubules preparation and transplantation, respectively. Third-passage DPCs with or without collagen gels were loaded into demineralized dentin tubules. Both types of grafts were transplanted into the rectus abdominis muscles of SD rats and were harvested after 21 days. The expression of alkaline phosphatase (ALP), bone sialoprotein (BSP), osteopontin (OPN), nestin, and dentin sialoprotein (DSP) was analyzed by immunohistochemistry. Histological analysis showed that DPCs in the collagen gel formed an osteodentin-like hard tissue matrix after 21 days. Increased positive immunoreactivity for ALP, BSP, OPN, nestin, and DSP was observed in experimental groups compared with control. Our results demonstrate that DPCs in collagen gel inside demineralized dentin tubules show increased growth and differentiation.</p> Sultan Zeb Khan, Sana Mirza, Samina Karim, Takashi Inoue, Mohammed S. Bin-Shuwaish, Laila Al Deeb, Khold Al Ahdal, Rana S. Al-Hamdan, Ahmed M. Maawadh, Fahim Vohra, Tariq Abduljabbar Copyright (c) 2020 Sultan Zeb Khan, Sana Mirza, Samina Karim, Takashi Inoue, Mohammed S. Bin-Shuwaish, Laila Al Deeb, Khold Al Ahdal, Rana S. Al-Hamdan, Ahmed M. Maawadh, Fahim Vohra, Tariq Abduljabbar Mon, 02 Nov 2020 00:00:00 +0100 Inflammation-related cytokines and their roles in gastroenteropancreatic neuroendocrine neoplasms <p>Proinflammatory counterworks are important at different stages of tumor development, particularly during invasion and metastasis. Immune cells and their signal molecules can influence all stages of tumor progression, as well as therapeutic intervention. Proinflammatory cytokines are known triggers of growth in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). In this study, we explored the immunohistochemical expression of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), IL-2, and IL-6 in tissues from 43 GEP-NEN patients with tumors of gastric, duodenal, ileal, appendiceal, and colonic origin. The immunohistochemical expression of TNF-α was increased in tumor groups with high proliferation rates (Ki-67; <em>p</em> = 0.034), as well as in those with higher tumor grades (<em>p</em> = 0.05). Moreover, the immunohistochemical expression of TNF-α positively correlated with death outcomes (<em>p</em> = 0.016). Expression of IL-6, IL-1β, and IL-2 displayed similar immunohistochemical expression patterns regardless of Ki-67, although the expression between the ILs differed. Most GEP-NENs had high levels of IL-6 and lower levels of IL-1β and IL-2. Although further comprehensive studies are required for a complete understanding of activated mechanisms in proinflammatory protumoral microenvironment of GEP-NENs, TNF-α is a potential marker in the prognosis of those tumors.</p> Davorka Herman Mahečić, Maja Cigrovski Berković, Vanja Zjačić-Rotkvić, Tamara Čačev, Sanja Kapitanović, Monika Ulamec Copyright (c) 2020 Davorka Herman Mahečić, Maja Cigrovski Berković, Vanja Zjačić-Rotkvić, Tamara Čačev, Sanja Kapitanović, Monika Ulamec Mon, 02 Nov 2020 00:00:00 +0100 Endothelial loss during the surgical procedure in saphenous veins harvested by open and endoscopic techniques in coronary artery bypass surgery <p>The patency of the vein graft in coronary artery bypass grafting could be dependent on the conventional open (vsO) or endoscopic (vsE) harvesting and on the hypoxic damage of endothelial cells. We aimed to evaluate both surgical techniques according to endothelial loss that occurs in the time between harvesting and implantation. Twenty-six saphenous veins were divided into vsO (n = 16) and vsE (n = 10) group. Three samples were taken from each vein. The first sample was taken after removal, the second before implantation of the distal part, and the third before the implantation of the proximal part, and they were stained with HE, Movat, and immunohistochemically with CD31. A significant loss of endothelial cells within both groups was found at the time of implantation of the distal and the proximal part of the vein graft compared to the endothelial cells at the time of harvesting. There were no significant differences in the endothelial loss between vsE and vsO groups at the time of harvesting and at the time before the implantation of the distal part. A higher number of endothelial cells was found in vsE group compared to vsO group at the time just before the implantation of the proximal part. The comparison of the implanted portions of vsE and vsO grafts to mammary arteries revealed a significant loss of endothelial cells only in vsO graft. We conclude that, at the time of implantation, the endothelial layer of the vein graft harvested endoscopically is more preserved than of the vein graft harvested openly.</p> Aleksandra Milutinović, Ruda Zorc-Pleskovič Copyright (c) 2020 Aleksandra Milutinović, Ruda Zorc-Pleskovič Mon, 02 Nov 2020 00:00:00 +0100 Percutaneous coronary intervention assisted by invasive mechanical ventilation and intra-aortic balloon pump for acute myocardial infarction with cardiogenic shock: Retrospective cohort study and meta-analyses <p>There is little evidence to recommend the optimal invasive mechanical ventilation (IMV) modes and ideal positive end-expiratory pressure stress levels for acute myocardial infarction-cardiogenic shock (AMI-CS) patients. The aim of this study was to compare the mortality outcome in patients with AMI-CS who were treated with percutaneous coronary intervention (PCI) assisted by intra-aortic balloon pump (IABP) + IMV with historical controls. From January 1, 2016 to June 1, 2017, 60 patients were retrospectively enrolled at Tianjin Chest Hospital. Out of these, 88.3% of patients achieved thrombolysis in myocardial infarction (TIMI) flow 3 after PCI. The all-cause mortality rate in-hospital and at 1 year was 25% (95% CI: 0.14–0.36) and 33.9% (0.22–0.46), respectively. A systematic review followed by meta-analysis was performed with four historical studies of patients treated by PCI + IMV with partial IABP, which found an in-hospital mortality rate of 66.0% (95% CI: 0.62–0.71). Recently, a meta-analysis of patients receiving PCI + IABP with partial IMV showed that the 1 year mortality rate was 52.2% (95% CI: 0.47–0.58). In Cox regression analysis of patient data from the current study, lactic acid level ≥4.5 mmol/L, hyperuricemia, and TIMI flow &lt;3 were independent predictors of death at 1 year. All-cause mortality, in-hospital and at 1 year, in patients with AMI-CS treated with PCI + IABP and IMV was lower than in those treated with PCI + partial IABP or IMV. Larger, longer-term direct comparisons are warranted.</p> Yin Liu, Chang-Ping Li, Peng-Ju Lu, Xu-Ying Wang, Jian-Yong Xiao, Ming-Dong Gao, Ji-Xiang Wang, Xiao-Wei Li, Nan Zhang, Chun-Jie Li, Jun Ma, Jing Gao Copyright (c) 2019 The author(s) Mon, 02 Nov 2020 00:00:00 +0100 Clinical Nocardia species: Identification, clinical characteristics, and antimicrobial susceptibility in Shandong, China <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 over 3 years in two tertiary general hospitals 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 the 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>Nocardia otitidiscaviarum</em> (40.7%). The antimicrobial susceptibility profiles varied between different <em>Nocardia</em> species. Notably, all<em> Nocardia</em> isolates were linezolid susceptible. The 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> Shu-Hua Lu, Zhen-Wen Qian, Pei-Pei Mou, Lian Xie Copyright (c) 2020 Shu-Hua Lu, Zhen-Wen Qian, Pei-Pei Mou, Lian Xie Mon, 02 Nov 2020 00:00:00 +0100 Chronic maxillary sinusitis of dental origin and oroantral fistula: The results of combined surgical approach in an Italian university hospital <p>Unilateral chronic maxillary sinusitis is a possible complication of odontogenic disease or dental treatment and is mainly due to the development of an oroantral fistula (OAF). The management of chronic maxillary sinusitis of dental origin (CMSDO) requires a combined treatment via endoscopic sinus surgery (ESS) and intraoral surgical treatment of the odontogenic source. The aim of this study is to present the results of our university hospital unit in the treatment and follow-up of a case series of 34 patients treated with a combined surgical approach for CMSDO due to OAF. All patients were treated with ESS combined with an intraoral approach. No intraoperative or immediate postoperative complications were observed; nasal synechia was found in 3 patients (8.82%). The overall success rate after the primary intervention was 94.12%; recurrence was observed in 2 cases (5.88%), both were suffering from diabetes mellitus and were tobacco smokers. Our results confirm that simultaneous surgery with a combination of an intraoral and endoscopic approach can be considered the best strategy for the long-term restoration of normal sinonasal homeostasis in selected patients with chronic odontogenic sinusitis and OAF, guaranteeing an effective treatment with minimal complications in the short and long term.</p> Massimo Galli, Giulia De Soccio, Fabrizio Cialente, Francesca Candelori, Francesca Romana Federici, Massimo Ralli, Marco de Vincentiis, Antonio Minni Copyright (c) 2020 Massimo Galli, Giulia De Soccio, Fabrizio Cialente, Francesca Candelori, Francesca Romana Federici, Massimo Ralli, Marco de Vincentiis, Antonio Minni Mon, 02 Nov 2020 00:00:00 +0100 Overexpression of microRNA-129-5p in glioblastoma inhibits cell proliferation, migration, and colony-forming ability by targeting ZFP36L1 <p>Glioblastoma multiforme (GBM) is a highly invasive cancer with a high recurrence rate. The prognosis of GBM patients remains poor, even after standard surgical resection combined with chemoradiotherapy. Thus, there is an urgent need for new therapeutic targets in GBM. In recent years, microRNAs have received considerable attention due to their important role in tumor development and progression. In this study, we investigated the role of miR-129-5p and miR-129-5p/ZFP36L1 axis in GBM tumorigenesis. Analysis of GSE103228 microarray data from the GEO database showed that miR-129-5p was significantly downregulated in GBM vs. normal brain tissues. Quantitative reverse transcription PCR analysis of miR-129-5p expression in seven GBM cell lines (LN229, A172, U87, T98G, U251, H4, and LN118) vs. normal human astrocytes (NHA) showed miR-129-5p was significantly downregulated in GBM cells. Overexpression of miR-129-5p in LN229 and A172 cells significantly suppressed cell proliferation, migration, invasion, and colony-forming ability. Target Scan analysis identified <em>ZFP36L1</em> as the target of miR-129-5p. UALCAN dataset analysis found that <em>ZFP36L1</em> was significantly upregulated in GBM vs. normal brain tissues, and high <em>ZFP36L1</em> expression was positively associated with poor survival of GBM patients. Western blot analysis demonstrated that ZFP36L1 was significantly upregulated in seven GBM cell lines vs. NHA. Overexpression of miR-129-5p in LN229 and A172 cells significantly inhibited ZFP36L1 mRNA and protein expression, while overexpression of ZFP36L1 in LN229 and A172 cells reversed miR-129-5p-mediated inhibition on GBM tumorigenesis. Our results revealed an important role of miR-129-5p in the negative regulation of <em>ZFP36L1</em> expression in GBM, suggesting new candidates for targeted therapy in GBM patients.</p> Xu Guo, Haozhe Piao, Ye Zhang, Peixin Sun, Bing Yao Copyright (c) 2019 Xu Guo, Haozhe Piao, Ye Zhang, Peixin Sun, Bing Yao Mon, 02 Nov 2020 00:00:00 +0100 High MTHFR promoter methylation levels in men confer protection against ischemic stroke <p>The <em>MTHFR</em> gene encodes methylenetetrahydrofolate reductase required for the metabolism of homocysteine (Hcy) – a previously reported independent risk factor for ischemic stroke (IS). In this study, we first aimed to clarify the association between DNA methylation levels in the <em>MTHFR</em> promoter and the risk of IS, followed by the analysis of potential interactions between environmental factors and DNA methylation levels that affect IS risk. We recruited 164 patients with hypertension and IS (case group) and 345 age-matched and sex-matched patients with hypertension only (control group). Demographic and clinical information was obtained using questionnaires, and blood samples were collected for biochemical analyses. Fluorescence quantitative methylation-specific PCR (qMSP) was used to detect <em>MTHFR</em> promoter methylation levels. A logistic regression analysis was performed to determine the relationship between environmental factors, <em>MTHFR</em> promoter methylation levels, and IS risk. We finally generated a receiver operating characteristic curve to determine whether <em>MTHFR</em> promoter methylation levels can predict IS. The mean <em>MTHFR</em> methylation levels in the case group (8.10 ± 6.14) were significantly lower than those in the control group (17.44 ± 3.16; <em>p &lt;</em> 0.05). <em>MTHFR</em> promoter methylation levels were also lower in patients with plasma Hcy levels ≥15 μmol/L (10.65 ± 4.05) than in those with Hcy levels &lt;15 μmol/L (16.74 ± 4.26, <em>p &lt;</em> 0.001). Finally, we found that <em>MTHFR</em> hypermethylation is a protective factor for IS, particular in men (OR in men: 0.07; 95% CI: 0.02–0.16; <em>p </em>&lt; 0.001). Further, sex and <em>MTHFR</em> promoter methylation levels exhibited a preliminary interaction effect on IS risk. These results indicate that <em>MTHFR</em> promoter methylation status might have diagnostic value in IS.</p> Shan Xu, Qianping Shi, Bo Li, Liyuan Han, Guodong Xu, Xiaolin Peng, Hongen Chen, Shuhong Dai, Wancheng Ma, Changyi Wang, Jianping Ma Copyright (c) 2020 Shan Xu, Qianping Shi, Bo Li, Liyuan Han, Guodong Xu, Xiaolin Peng, Hongen Chen, Shuhong Dai, Wancheng Ma, Changyi Wang, Jianping Ma Mon, 02 Nov 2020 00:00:00 +0100 DNA methylation of AHCY may increase the risk of ischemic stroke <p>Genetic factors play an important role in the pathogenesis of ischemic stroke. Of these, epigenetic modifications provide a new direction for the study of ischemic stroke pathogenesis. This study aimed to determine the correlation between DNA methylation of the gene encoding S-adenosylhomocysteine hydrolase (<em>AHCY</em>) and the risk of ischemic stroke in 64 ischemic stroke patients and 138 patients with traumatic brain injury (control group). The methylation level of <em>AHCY</em> was analyzed using quantitative methylation-specific polymerase chain reaction. Statistically significant differences in <em>AHCY</em> methylation levels were observed between the case group [medians (interquartile range): 0.13% (0.09%, 0.27%)] and the control group [0.06% (0.00%, 0.17%), <em>p</em> &lt; 0.0001], and these associations remained significant in both male (<em>p</em> = 0.003) and female (<em>p</em> = 0.0005) subjects. A subgroup analysis by age revealed a considerably higher percentage of methylated <em>AHCY</em> in the case group than the control group in all age groups (age &lt; 60 years, <em>p</em> = 0.007; age ≥ 60 years, <em>p</em> &lt; 0.0001). A receiver operating characteristic (ROC) curve analysis revealed a trend toward a role for <em>AHCY</em> methylation as an indicator of risk in all ischemic patients [area under the curve (AUC) = 0.70, <em>p</em> = 0.0001], male patients (AUC = 0.67, <em>p</em> = 0.004), and female patients (AUC = 0.75, <em>p</em> = 0.0002). Our study confirmed a significant association between the <em>AHCY</em> DNA methylation level and the risk of ischemic stroke, suggesting that this gene methylation pattern may be a potential diagnostic marker of ischemic stroke.</p> Lei Zhao, Xiaosheng Chen, Shengjun Zhou, Zhiqing Lin, Xi Yu, Yi Huang Copyright (c) 2020 Lei Zhao, Xiaosheng Chen, Shengjun Zhou, Zhiqing Lin, Xi Yu, Yi Huang Mon, 02 Nov 2020 00:00:00 +0100 Monomeric C-reactive protein affects cell injury and apoptosis through activation of p38 mitogen-activated protein kinase in human coronary artery endothelial cells <p>C-reactive protein (CRP) is an important predictor of cardiovascular events and plays a role in vascular inflammation and vessel damage. The aim of this study was to investigate the effect of pentameric CRP (pCRP) and monomeric CRP (mCRP) on the production of atherosclerosis-re­lated factors in cultured human coronary artery endothelial cells (HCAECs). HCAECs were treated with pCRP, mCRP, p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580, or transfected with p38 MAPK siRNA. Western blotting was performed to detect the expression of vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), intercellular adhesion molecule-2 (ICAM-2) and vascular cell adhe­sion molecule-1 (VCAM-1). Proliferation, damage, and apoptosis of HCAECs were examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, lactate dehydrogenase (LDH), and flow cytometry, respectively. mCRP suppressed VEGF and COX-2 expression and enhanced ICAM-2 and VCAM-1 expression in HCAECs, in both dose-dependent and time-dependent manner. Except at 100 μg/ml concen­tration and 20-hour or 24-hour incubation, pCRP had no apparent effects. mCRP but not pCRP induced HCAEC injury and phosphorylation of p38 MAPK, and the inhibitor SB203580 reversed the effects of mCRP. mCRP promotes injury and apoptosis of HCAECs through a p38 MAPK-dependent mechanism, which provides a new therapy for the injury of HCAECs in atherosclerosis.</p> Yong Zhang, Hongxia Cao Copyright (c) 2020 Yong Zhang, Hongxia Cao Mon, 02 Nov 2020 00:00:00 +0100 Human brucellosis in pregnancy – an overview <p>Human brucellosis during pregnancy is characterized by significantly less pronounced adverse obstetric outcomes than in animals, but with remarkably more adverse obstetric outcomes when compared to healthy pregnant women. Seroprevalence of brucellosis in pregnancy and cumulative incidence of brucellosis cases per 1000 delivered obstetrical discharges in endemic regions were reported to be 1.5–12.2% and 0.42–3.3, respectively. Depending on the region, the frequency of pregnant women in the cohorts of patients with brucellosis was from 1.5% to 16.9%. The most common and the most dramatic unfavorable outcomes during brucellosis in pregnancy are the obstetric ones, manifested as abortions (2.5–54.5%), intrauterine fetal death (0–20.6%), or preterm deliveries (1.2–28.6%), depending on the stage of pregnancy. Other unfavorable outcomes due to brucellosis are addressed to infant (congenital/neonatal brucellosis, low birth weight, development delay, or even death), the clinical course of disease in mother, and delivery team exposure. When diagnosed in pregnant women, brucellosis should be treated as soon as possible. Early administration of adequate therapy significantly reduces the frequency of adverse outcomes. Rifampicin in combination with trimethoprim-sulfamethoxazole for 6 weeks is the most commonly used and recommended regimen, although monotherapies with each of these two drugs are also widely used while waiting for the results from prospective randomized therapeutic trials. As no effective human vaccine exists, screening of pregnant women and education of all women of childbearing age about brucellosis should be compulsory preventive measures in endemic regions.</p> Mile Bosilkovski, Jurica Arapović, Fariba Keramat Copyright (c) 2019 BJBMS Mon, 02 Nov 2020 00:00:00 +0100 Can telomere length predict bone health? A review of current evidence <p>Telomeres are repetitive DNA sequences located at the end of chromosomes that serve as a protective barrier against chromosomal deterioration during cell division. Approximately 50–200 base pairs of nucleotides are lost per cell division, and new repetitive nucleotides are added by the enzyme telomerase, allowing telomere maintenance. Telomere shortening has been proposed as an indicator for biological aging, but its relationship with age-related osteoporosis is ambiguous. We summarize the current evidence on the relationship between telomere length and bone health in experimental and epidemiological studies, which serve as a scientific reference for the development of novel diagnostic markers of osteoporosis or novel therapeutics targeting telomere and telomerase of bone cells to treat osteoporosis.</p> Sok Kuan Wong, Soelaiman Ima-Nirwana, Kok-Yong Chin Copyright (c) 2020 Sok Kuan Wong, Soelaiman Ima-Nirwana, Kok-Yong Chin Mon, 02 Nov 2020 00:00:00 +0100