Bosnian Journal of Basic Medical Sciences <p>The BJBMS (Bosnian Journal of Basic Medical Sciences) is а premier venue for discoveries in basic and clinical biomedical science. The BJBMS was founded in 1998 and is published by the Association of Basic Medical Sciences, a nonprofit honor organization of physician-scientists.</p> <p>Broad readership and scope. The BJBMS reaches readers across a wide range of medical disciplines and sectors. The journal publishes basic and translational/clinical research submissions and reviews in all biomedical specialties, including Genetics and Molecular biology, Immunology, Microbiology, Pathology, Biochemistry, Pharmacology, Anatomy, Biomaterials, new and emerging research and diagnostic methods, new and emerging medical entities, and others.</p> Association of Basic Medical Sciences of FBIH en-US Bosnian Journal of Basic Medical Sciences 1512-8601 Predictive performance of CT for adverse outcomes among COVID-19 suspected patients: a two-center retrospective study <p>The aim of the study was to compare the performance of various computed tomography (CT) reporting tools, including zonal CT visual score (ZCVS), the number of involved lobes, and Radiological Society of North America (RSNA) categorization in predicting adverse outcomes among patients hospitalized due to the lower respiratory symptoms during the coronavirus disease 2019 (COVID-19) pandemic. A total of 405 patients admitted with severe respiratory symptoms who underwent a chest CT were enrolled. The primary adverse outcome was intensive care unit (ICU) admission of patients. Predictive performances of reporting tools were compared using the area under the receiver operating characteristic curves (AUC ROC). Among the 405 patients, 39 (9.63%) required ICU support during their hospital stay. At least two or more observers reported a typical and indeterminate COVID-19 pneumonia CT pattern according to RSNA categorization in 70% (285/405) of patients. Among these, 63% (179/285) had a positive polymerase chain reaction (PCR test for the SARS-CoV-2 virus. The median number of lobes involved according to CT was higher in patients who required ICU support (median interquartile range [IQR], 5[3; 5] vs. 3[0; 5]). The median ZCVS score was higher among the patients that subsequently required ICU support (median [IQR], 4[0; 12] vs. 13[5.75; 24]). The bootstrap comparisons of AUC ROC showed significant differences between reporting tools, and the ZCVS was found to be superior (AUC ROC, 71-75%). The ZCVS score at the first admission showed a linear and significant association with adverse outcomes among patients with the lower respiratory tract symptoms during the COVID-19 pandemic.</p> Begümhan Baysal Mahmut Bilal Dogan Mutlu Gulbay Mine Sorkun Murathan Koksal Aliye Bastug Sumeyye Kazancioglu Bahadir Orkun Ozbay Sacit Icten Ferhat Arslan Yasemin Cag Hurrem Bodur Haluk Vahaboglu Copyright (c) 2021 Begümhan Baysal, Mahmut Bilal Dogan, Mutlu Gulbay, Mine Sorkun, Murathan Koksal, Aliye Bastug, Sumeyye Kazancioglu, Bahadir Orkun Ozbay, Sacit Icten, Ferhat Arslan, Yasemin Cag, Hurrem Bodur, Haluk Vahaboglu 2021-12-01 2021-12-01 21 6 739 745 10.17305/bjbms.2020.5466 Efficacy of chemotherapeutics in classic and non-classic Kaposi sarcoma: A single-center retrospective real-world data <p>Kaposi sarcoma is a rare disease and there is a gap in the literature about which chemotherapeutics should be applied, especially for the classical type. We aimed to present our institutional data on the demographic characteristics, treatment, and treatment efficacy in 16 Kaposi sarcoma (KS) patients treated with chemotherapy. We retrospectively analyzed the demographic and clinical characteristics, and the chemotherapeutic agents administered to the 16 KS patients diagnosed in our center and treated with chemotherapy, based on the medical records obtained. The median age, gender, type of KS, site of involvement, cytotoxic agents administered, progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety profiles of the patients were evaluated. The median age at disease onset was 61.07 years (range, 39.4–85.8 years). Among the patients, 1 had immunosuppression-related KS, 4 had AIDS-related KS, and 11 had classical KS. In the first-line cytotoxic therapy, 7 patients received pegylated-liposomal doxorubicin (PLD), 6 patients received paclitaxel, 2 patients received oral etoposide, and 1 patient received the adriamycin, bleomycin, and vincristine regimen. In the Kaplan–Meier analysis, the PFS was 39.9 months (95% CI, 7.7–72.0). In the first-line setting, a significant difference in terms of PFS was observed between the PLD- and paclitaxel-treated groups (not reached vs. 12.8 months, <em>p</em> = 0.033). The OS was 66.1 months (95% CI, 30.2–102.0). The ORR of the 16 patients was 43.8%, and their DCR was 81.3%. No grade 3 or 4 toxicity was observed. This retrospective study showed that PLD seems better than paclitaxel in terms of PFS and response rates and it has shown to have a good safety profile in KS patients.</p> Sibel Oyucu Orhan Ahmet Bilgehan Sahin Erdem Cubukcu Adem Deligonul Birol Ocak Bedrettin Orhan Turkkan Evrensel Copyright (c) 2021 Sibel Oyucu Orhan, Ahmet Bilgehan Sahin, Erdem Cubukcu, Adem Deligonul, Birol Ocak, Bedrettin Orhan, Turkkan Evrensel 2021-12-01 2021-12-01 21 6 746 751 10.17305/bjbms.2020.5329 Clinicopathological characteristics and survival in lung signet ring cell carcinoma: a population-based study <p>Lung signet-ring cell carcinoma (LSRCC) is a very rare type of lung cancer, the clinical characteristics, and prognosis of which remain to be clarified. In order to explore the clinicopathological and survival-related factors associated with LSRCC, we performed a large population-based cohort analysis of data included in the Surveillance, Epidemiology, and End Results (SEER) registry from 2001 to 2015. A total of 752 LSRCC and 7518 lung mucinous adenocarcinoma (LMAC) patients were incorporated into our analysis, with respective mean ages of 63.8 and 67.5 years at the time of diagnosis. LSRCC patients were significantly more likely than LMAC patients to have distant-stage disease (72.1% vs. 45.8%, <em>p </em>&lt; 0.0001), tumors of a high pathological grade (40.6% vs. 10.8%, <em>p </em>&lt; 0.0001), have undergone chemotherapy (62.1% vs. 39.9%, p&lt;0.0001), be male (52.7% vs. 48.5%, <em>p </em>= 0.03), and be &lt; 40 years old (3.3% vs. 1.3%, <em>p </em>= 0.022), whereas they were less likely to have undergone surgical treatment (52.4% vs. 77.0%, <em>p </em>&lt; 0.0001). LSRCC and LMAC patients exhibited median overall survival (OS) duration of 8 and 18 months (<em>p </em>&lt; 0.0001), respectively, although these differences were not significant after adjusting for confounding variables. Independent factors associated with a favorable patient prognosis included a primary site in the middle or lower lung lobe, underwent surgery, and underwent chemotherapy. However, age ≥80 years, higher grade, distant summary stage disease, and T4 stage disease were linked to poor prognosis. Patient age, tumor grade, primary tumor site, summary stage, T stage, surgery, and chemotherapy were all significantly associated with LSRCC patient prognosis.</p> Yunting Cai Yan Xie Yanli Xiong Wei Guan Yu Pu Dong Wang Mingfang Xu Shenglan Meng Copyright (c) 2021 Yunting Cai , Yan Xie , Yanli Xiong , Wei Guan , Yu Pu, Dong Wang, Mingfang Xu, Shenglan Meng 2021-12-01 2021-12-01 21 6 752 759 10.17305/bjbms.2020.5454 Construction and verification of prognostic nomogram for early-onset esophageal cancer <p>This study aimed to build up nomogram models to evaluate overall survival (OS) and cancer-specific survival (CSS) in early-onset esophageal cancer (EOEC). Patients diagnosed with esophageal cancer (EC) from 2004 to 2015 were extracted from the Surveillance Epidemiology and End Results (SEER) database. Clinicopathological characteristics of younger versus older patients were compared, and survival analysis was performed in both groups. Independent related factors influencing the prognosis of EOEC were identified by univariate and multivariate Cox analysis, which were incorporated to construct a nomogram. The predictive capability of the nomogram was estimated by the concordance index (C-index), calibration plot, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). A total of 534 younger and 17,243 older patients were available from the SEER database. Younger patients were randomly segmented into a training set (n = 266) and a validation set (n = 268). In terms of the training set, the C-index of the OS nomogram was 0.740 (95% CI: 0.707-0.773), and that of the CSS nomogram was 0.752 (95% CI: 0.719-0.785). In view of the validation set, the C-index of OS and CSS were 0.706 (95% CI: 0.671-0.741) and 0.723 (95% CI: 0.690-0.756), respectively. Calibration curves demonstrated the consistent degree of fit between actual and predicted values in nomogram models. From the perspective of DCA, the nomogram models were more beneficial than the tumor-node-metastasis (TNM) and the SEER stage for EOEC. In brief, the nomogram model can be considered as an individualized quantitative tool to predict the prognosis of EOEC patients to assist clinicians in making treatment decisions.</p> Xiaoxiao Liu Wei Guo Xiaobo Shi Yue Ke Yuxing Li Shupei Pan Yingying Jin Yuchen Wang Qinli Ruan Hongbing Ma Copyright (c) 2021 Xiaoxiao Liu, Wei Guo, Xiaobo Shi, Yue Ke, Yuxing Li; Shupei Pan, Yingying Jin, Yuchen Wang, Qinli Ruan; Hongbing Ma 2021-12-01 2021-12-01 21 6 760 772 10.17305/bjbms.2021.5533 Effects of L-dopa on expression of prolactin and synaptotagmin IV in 17-beta-estradiol-induced prolactinomas of ovariectomized hemiparkinsonian rats <p>Parkinson’s disease (PD) is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. Dopamine precursor levodopa (L-dopa) is used as the first-line treatment for PD. Evidence suggests neuroprotective effects of estrogens in PD. Since both 17b-estradiol (E2) and L-dopa act as regulators of prolactin (PRL) secretion from the pituitary gland, we investigated their effect on the expression of PRL in prolactinomas that developed in ovariectomized hemiparkinsonian rats treated with E2. We also investigated the effect of E2 and L-dopa on the expression of synaptotagmin IV (Syt IV), an immediate early gene whose product is abundant in the pituitary gland and was found to be highly co-expressed with PRL in lactotrophs (&gt;90%). The hemiparkinsonian rat model was obtained by unilateral lesioning of dopaminergic nigrostriatal neurons. Rats received silastic tubing implants with E2 and were treated with L-dopa. Enzyme-linked immunosorbent assay and immunohistochemistry were used to assess the serum concentrations of PRL and E2 and expression of PRL and Syt IV in the tissue of adenohypophysis, respectively. We found that high levels of serum E2 were associated with the upregulation of Syt IV and PRL in PRL-ir cells, while treatment with L-dopa decreased the size of prolactinomas and downregulated Syt IV but had no effect on PRL expression or serum concentrations.</p> Maja Zorovic Kaja Kolmančič Marko Živin Copyright (c) 2021 Maja Zorovic, Kaja Kolmančič, Marko Živin 2021-12-01 2021-12-01 21 6 702 711 10.17305/bjbms.2021.5491 Chronic mechanical irritation and oral squamous cell carcinoma: A systematic review and meta-analysis <p>The objective of the present article was to qualitatively and quantitatively review the association between chronic mechanical irritation and oral squamous cell carcinoma (OSCC). PubMed, SCOPUS, and Web of Science databases were searched using the keyword combinations “chronic trauma and oral squamous cell carcinoma; chronic irritation and oral squamous cell carcinoma; chronic irritation and oral cancer; and chronic trauma and oral cancer.” Duplicates and irrelevant articles were excluded after the title and abstract screening. The full texts of the remaining articles were assessed using selection criteria. A total of 375 (PubMed-126; SCOPUS-152; WOS-97) articles were screened, and 343 duplicates and irrelevant articles were excluded from the study. Only 9 of the remaining 32 articles met the selection criteria and were included in the qualitative analysis. Buccal mucosa and tongue, being highly prone to chronic irritation through the dental prosthesis, were the common sites for OSCC. Edentulous subjects with ill-fitting dentures were at a high risk of developing chronic irritation associated-OSCC. According to the Joanna Briggs Institute of risk assessment, eight of the nine included studies had a low risk of bias. The quantitative analysis showed a significant association (<em>p </em>&lt; 0.00001) between the chronic oral mucosal irritation and OSCC with an overall risk ratio of 2.56 at a confidence interval of 1.96-3.35. Chronic oral mucosa irritation has a significant association with OSCC, and the nature of association could be that of a potential co-factor (dependent risk factor) rather than an independent risk factor.</p> Archana A. Gupta Supriya Kheur Saranya Varadarajan Sameena Parveen Harisha Dewan Yaser Ali Alhazmi Thirumal A. Raj Luca Testarelli Shankargouda Patil Copyright (c) 2021 Supriya Kheur, Saranya Varadarajan, Sameena Parveen, Harisha Dewan, Yaser Ali Alhazmi, Thirumal A. Raj , Luca Testaralli, Shankargouda Patil 2021-12-01 2021-12-01 21 6 647 658 10.17305/bjbms.2021.5577 Integrated profiling identifies ITGB3BP as prognostic biomarker for hepatocellular carcinoma <p>Hepatocellular carcinoma (HCC) is a highly malignant tumor. In this study, we sought to identify a novel biomarker for HCC by analyzing transcriptome and clinical data. The R software was used to analyze the differentially expressed genes (DEGs) in the datasets GSE74656 and GSE84598 downloaded from the Gene Expression Omnibus database, followed by a functional annotation. A total of 138 shared DEGs were screened from two datasets. They were mainly enriched in the “Metabolic pathways” pathway (Padj = 8.21E-08) and involved in the carboxylic acid metabolic process (Padj = 0.0004). The top 10 hub genes were found by protein-protein interaction analysis and were upregulated in HCC tissues compared to normal tissues in The Cancer Genome Atlas database. Survival analysis distinguished 8 hub genes CENPE, SPDL1, Hyaluronan-mediated motility receptor, Rac GTPase activating protein 1, Thyroid hormone receptor interactor 13, cytoskeleton-associated protein (CKAP) 2, CKAP5, and Integrin subunit beta 3 binding protein (ITGB3BP) were considered as prognostic hub genes. Multivariate cox regression analysis indicated that all the prognostic hub genes were independent prognostic factors for HCC. Furthermore, the receiver operating characteristic curve revealed that the 8-hub genes model had better prediction performance for overall survival compared to the T stage (<em>p </em>= 0.008) and significantly improved the prediction value of the T stage (<em>p </em>= 0.002). The Human Protein Atlas showed that the protein expression of ITGB3BP was upregulated in HCC, so the expression of ITGB3BP was further verified in our cohort. The results showed that ITGB3BP was upregulated in HCC tissues and was significantly associated with lymph node metastasis.</p> Qiuli Liang Chao Tan Feifei Xiao Fuqiang Yin Meiliang Liu Lei Lei Liuyu Wu Yu Yang Hui Juan Jennifer Tan Shun Liu Xiaoyun Zeng Copyright (c) 2021 Qiuli Liang, Chao Tan, Feifei Xiao, Fuqiang Yin, Meiliang Liu, Lei Lei, Liuyu Wu, Yu Yang, Hui Juan Jennifer Tan, Shun Liu, Xiaoyun Zeng 2021-12-01 2021-12-01 21 6 712 723 10.17305/bjbms.2021.5690 The preoperative hemoglobin, albumin, lymphocyte and platelet (HALP) score is a useful predictor in patients with resectable esophageal squamous cell carcinoma <p>The hemoglobin, albumin, lymphocyte and platelet (HALP) score has been confirmed as a prognostic factor in several types of cancers. The current study aimed to assess the prognostic value of preoperative HALP score, an inflammatory and nutritional based score, in predicting cancer-specific survival (CSS) in resectable patients undergoing curative resection for esophageal squamous cell carcinoma (ESCC). The clinical data of 355 consecutive patients with ESCC who underwent curative resection were retrospectively conducted and analyzed. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value for preoperative HALP. The areas under the curve (AUC) for preoperative HALP and other variables were calculated and compared. Cox regression analyses and Kaplan–Meier methods were used to identify the factors associated with CSS. According to the ROC curve, the optimal cut-off value for preoperative HALP was 31.8. The 5-year CSS for preoperative HALP low (≤31.8) and high (&gt;31.8) was 15.1% and 47.5%, respectively (<em>p </em>&lt; 0.001). Preoperative HALP had reliable abilities to predict CSS in resectable ESCC patients in any stage or gender, according to the subgroup analysis based on the patients’ cancer stage and gender. Multivariate analyses confirmed that preoperative HALP was an independent prognostic score regarding CSS in patients with resectable ESCC (<em>p </em>&lt; 0.001). This study confirmed that the postoperative HALP score could be regarded as a potential independent prognostic factor for CSS in patients with resectable ESCC.</p> Ji-Feng Feng Liang Wang Xun Yang Copyright (c) 2021 Ji-Feng Feng, Liang Wang, Xun Yang 2021-12-01 2021-12-01 21 6 773 781 10.17305/bjbms.2021.5666 Analysis of the diagnostic and prognostic value of miR-9-5p in carotid artery stenosis <p>More and more evidence shows that microRNAs (miRNAs) play an important role in the diagnosis and prognosis of human diseases. In this study, we investigated the diagnostic value of miR-9-5p for asymptomatic carotid artery stenosis (CAS) and its predictive value for future cerebrovascular events within 5 years. A total of 88 asymptomatic CAS patients and 86 healthy individuals were recruited. The expression level of serum miR-9-5p was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic value of miR-9-5p in CAS was assessed by a receiving operator characteristic (ROC) curve. The predictive value of miR-9-5p for the occurrence of cerebrovascular events was evaluated by the Kaplan-Meier method. The serum level of miR-9-5p was significantly decreased in asymptomatic CAS patients. ROC curve had an AUC value of 0.910, with the sensitivity and specificity of 80.7% and 87.2% at the cut-off value of 0.72, respectively. A total of 25 patients had cerebrovascular events during the 5-year follow-up, including 3 strokes and 22 transient ischemic attacks<strong>&nbsp;</strong>(TIAs). Kaplan-Meier survival analysis revealed that the low expression level of miR-9-5p was an independent factor closely related to the occurrence of cerebrovascular events. Serum miR-9-5p could be used as a new biomarker for the diagnosis of CAS, and the low expression of miR-9-5p is associated with poor prognosis.</p> Hongxin Liu Juan Zhou Wei Jiang Feng Wang Copyright (c) 2021 Hongxin Liu, Juan Zhou, Wei Jiang, Feng Wang 2021-12-01 2021-12-01 21 6 724 729 10.17305/bjbms.2021.5545 Pharmacogenetics of new classes of antidiabetic drugs <p>Type 2 diabetes (T2D) has a continuously rising prevalence worldwide. Pharmacogenetics has been recognized as a promising concept for pharmacological treatment of T2D, as antidiabetic drugs are not equally effective and safe for all patients, and the costs of diabetes treatment are increasing. The latest published guidelines on T2D treatment firmly endorse the use of newer antidiabetic drugs, sodium-glucose cotransporter-2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP-IVi), and glucagon-like peptide-1 receptor agonists (GLP-1RA), considering their satisfactory pharmacological effect and good safety profile. Furthermore, SGLT2i and GLP-1RA show protective effects in patients with established atherosclerotic cardiovascular disease and chronic kidney disease. However, there has been growing evidence that the effectiveness and safety of these drug classes could depend on genetic variability. Here, we summarized the results of the published studies on the pharmacogenetic biomarkers for the three drug classes. A number of genetic variations have been investigated so far. The explored candidate genes mostly encode drug targets, drug-metabolizing enzymes, and genes linked to T2D risk. Although many of the results are promising, it is still necessary to obtain more information from larger controlled studies to confirm their clinical significance. This approach may lead towards more personalized treatment for patients with T2D.</p> Selma Imamovic Kadric Aida Kulo Cesic Tanja Dujic Copyright (c) 2021 Selma Imamovic Kadric, Aida Kulo Cesic, Tanja Dujic 2021-12-01 2021-12-01 21 6 659 671 10.17305/bjbms.2021.5646 Letter regarding “Chronic mechanical irritation and oral squamous cell carcinoma: A systematic review and meta-analysis” <p>Dear Editor:</p> <p>We have read with a great interest the article by Gupta et al. [1] who performed a meta-analysis exploring the association between chronic mechanical irritation and oral squamous cell carcinoma. The conclusion of the meta-analysis is that chronic oral mucosa irritation has a significant association with oral squamous cell carcinoma, and the nature of association could be that of a potential co-factor (dependent risk factor) rather than an independent risk factor.</p> <p>Read more in <a href="">PDF.</a></p> Jian Xie Lang Li Copyright (c) 2021 Jian Xie, Lang Li 2021-12-01 2021-12-01 21 6 788 788 10.17305/bjbms.2021.5939 Reply to the letter regarding “Chronic mechanical irritation and oral squamous cell carcinoma: A systematic review and meta-analysis” <p>Dear Editor,</p> <p>We thank Dr. Jian Xie for the valuable inputs on our paper titled ‘Chronic mechanical irritation and oral squamous cell carcinoma: A systematic review and meta-analysis [1].’ The first concern of Dr. Xie was that we had included two studies that were based on the same population. We re-examined these papers, one was published in 2010 [2] and the other in 2017 [3] by the same group of authors. Given the significant time difference between the two papers, we did not want to presume they were from the same sample population. There is no clear evidence that they are from the same sample population.</p> <p>Read more in <a href="">PDF</a>.</p> Archana A Gupta Supriya Kheur Saranya Varadarajan Sameena Parveen Harisha Dewan Yaser Ali Alhazmi A. Thirumal Raj Luca Testarelli Shankargouda Patil Copyright (c) 2021 Archana A Gupta, Supriya Kheur, Saranya Varadarajan, Sameena Parveen, Harisha Dewan, Yaser Ali Alhazmi, A. Thirumal Raj, Luca Testarelli, Shankargouda Patil 2021-12-01 2021-12-01 21 6 787 787 10.17305/bjbms.2021.6006 Skeletal muscle and fiber type-specific intramyocellular lipid accumulation in obese mice <p>In obesity, accumulation of lipid droplets in skeletal muscle fibers and a shift towards fast muscle fiber types can both contribute to insulin resistance. However, it is not yet clear how intramyocellular lipid accumulation and fiber type changes are associated. Therefore, we investigated to what extent the lipids accumulated in a fiber type-specific manner in the functionally similar fast-, intermediate- and slow-twitch gastrocnemius, plantaris, and soleus muscles, respectively, in high-fat diet-induced obese 54-week-old female C57BL/6JOlaHsd mice (n = 9) compared to control standard-diet-treated lean mice (n = 9). A high-fat diet was administered for 26 weeks. Fiber-type specific intramyocellular lipid content analysis and muscle fiber typing were performed using histochemical analysis of lipids with Sudan Black and immunohistochemical analysis of myosin heavy chains on serial sections of skeletal muscles. Compared to the lean mice, the lipid accumulation was most prominent in types 2a and 2x/d fibers (<em>p </em>&lt; 0.05) of fast-twitch gastrocnemius and intermediate plantaris muscles in the obese mice, while in slow-twitch soleus muscle, there was no significant lipid accumulation in the obese animals. Furthermore, the slow-twitch soleus muscle of the obese mice with no significant change in muscle fiber diameters exhibited the most pronounced shift towards fast-type myosin heavy chain isoform expression (<em>p </em>&lt; 0.05). In contrast, the fast-twitch and intermediate-twitch gastrocnemius and plantaris muscles, respectively, in which the muscle fiber diameters increased (<em>p </em>&lt; 0.05), were more resistant toward myosin heavy chain expression changes. In conclusion, we demonstrated both muscle- and fiber-type specificity in intramyocellular lipid accumulation in obese mice, suggesting that in obesity, similar muscle fiber types in different muscles accumulate lipids differentially.</p> Nejc Umek Simon Horvat Erika Cvetko Copyright (c) 2021 Nejc Umek, Simon Horvat, Erika Cvetko 2021-12-01 2021-12-01 21 6 730 738 10.17305/bjbms.2021.5876 How are central foveal and choroidal thickness affected in patients with mild COVID-19 infection? <p>The aim of this study was to evaluate the effects of&nbsp; COVID-19 on central foveal and choroidal thicknesses. Thirty-two patients with a positive SARS-CoV-2 PCR test who received outpatient treatment within the previous two months and 32 healthy controls were included in the study. Patients requiring hospitalization due to COVID-19 as well as the patients who received either intensive care support and/or antiplatelet therapy, smokers, or patients with systemic or ocular diseases were excluded from the study. After full ophthalmological examination, central foveal and choroidal thicknesses were evaluated by using optical coherence tomography. Statistical analysis of the study data demonstrated no significant difference between the groups in terms of age or gender (<em>p</em>&gt;0.05). There was also no statistically significant difference between the groups in terms of central foveal thickness, central choroidal thickness, or nasal 500, nasal 1500, temporal 500, or temporal 500-micron distances (<em>p</em>&gt;0.05 for all parameters). Choroidal and retinal thicknesses were not affected in patients with recent mild COVID 19 without comorbidities.</p> Müge Fırat Sabiha Kobat Copyright (c) 2021 Müge Fırat 2021-12-01 2021-12-01 21 6 782 786 10.17305/bjbms.2021.5840 Therapeutic effects of stem cells in different body systems, a novel method that is yet to gain trust: A comprehensive review <p><span style="font-weight: 400;">Stem cell therapy has been used to treat several types of diseases, and it is expected that its therapeutic uses shall increase as novel lines of evidence begin to appear. Furthermore, stem cells have the potential to make new tissues and organs. Thus, some scientists propose that organ transplantation will significantly rely on stem cell technology and organogenesis in the future. Stem cells and its robust potential to differentiate into specific types of cells and regenerate tissues and body organs, have been investigated by numerous clinician scientists and researchers for their therapeutic effects. Degenerative diseases in different organs have been the main target of stem cell therapy. Neurodegenerative diseases such as Alzheimer's, musculoskeletal diseases such as osteoarthritis, congenital cardiovascular diseases, and blood cell diseases such as leukemia are among the health conditions that have benefited from stem cell therapy advancements. One of the most challenging parts of the process of incorporating stem cells into clinical practice is controlling their division and differentiation potentials. Sometimes, their potential for&nbsp; uncontrolled growth will make these cells tumorigenic. Another caveat in this process is the ability to control the differentiation process. While stem cells can easily differentiate into a wide variety of cells,&nbsp; a paracrine effect controlled activity, being in an appropriate medium will cause abnormal differentiation leading to treatment failure. In this review, we aim to provide an overview of the therapeutic effects of stem cells in diseases of various organ systems. In order to advance this new treatment to its full potential, researchers should focus on establishing methods to control the differentiation process, while policymakers should take an active role in providing adequate facilities and equipment for these projects. Large population clinical trials are a necessary tool that will help build trust in this method. Moreover, improving social awareness about the advantages and adverse effects of stem cell therapy is required to develop a rational demand in the society, and consequently, healthcare systems should consider established stem cell-based therapeutic methods in their treatment algorithms.</span></p> <p>&nbsp;</p> Alireza Ebrahimi Hanie Ahmadi Zahra Pourfraidon Ghasrodashti Nader Tanide Reza Shahriarirad Amirhossein Erfani Keivan Ranjbar Soheil Ashkani-Esfahani Copyright (c) 2021 Alireza Ebrahimi , Hanie Ahmadi, Zahra Pourfraidon Ghasrodashti, Nader Tanide, Reza Shahriarirad , Amirhossein Erfani, Keivan Ranjbar , Soheil Ashkani-Esfahani 2021-12-01 2021-12-01 21 6 672 701 10.17305/bjbms.2021.5508 Protocatechuic acid as an inhibitor of the JNK/CXCL1/CXCR2 pathway relieves neuropathic pain in CCI rats <p><span style="font-weight: 400;">Emerging evidence has shown that protocatechuic acid (PCA) has antioxidant and anti-inflammatory effects. It can alleviate the injury of sciatic nerve, while the mechanism of its therapeutic effect on neuralgia remains unknown . In vivo, chromium bowel ligation was used to establish a chronic constriction injury (CCI) rat model to induce sciatic nerve pain, then two doses of PCA were used to treat CCI rats. In vitro, 10 ng/mL TNF-α was used to stimulate glial satellite cells derived from the dorsal root ganglia (DRG) L4-L6 of the sciatic nerve to simulate sciatic nerve pain. PCA relieved mechanical allodynia and thermal hyperalgesia in CCI rats. CCK-8 assay revealed that PCA inhibited the proliferation of glial satellite cells induced by TNF-α. Moreover, ELISA demonstrated that PCA could improve the inflammatory response of rats caused by CCI and cells induced by TNF-α. Next, RT-qPCR and Western blot assays testified that PCA blocked the c-Jun N-terminal kinase/the chemokine ligand 1/CXC chemokine receptor 2 (JNK/CXCL1/CXCR2) pathway by inhibiting CXCL1 levels in cells induced by TNF-α and DRG of CCI rats. In conclusion, PCA can alleviate neuropathic pain of CCI rats, improve oxidative stress by inhibiting the JNK/CXCL1/CXCR2 signaling pathway, which provides a new perspective for the treatment of neuropathic pain caused by CCI.</span></p> Hong-xia Chang Yue-feng Zhao Copyright (c) 2021 Hong-xia Chang, Yue-feng Zhao 2021-11-23 2021-11-23 21 6 10.17305/bjbms.2021.5928 Clinical features and major bleeding predictors for 161 fatal cases of COVID-19: A retrospective observational study <p><span style="font-weight: 400;">The aim of this study was to investigate the patient characteristics and laboratory parameters for COVID-19 non-survivors as well as to find risk factors for major bleeding complications. For this retrospective study, the data of patients who </span><span style="font-weight: 400;">died</span><span style="font-weight: 400;"> with COVID-19 in our intensive care unit were collected in the period of March 20 - April 30, 2020. D-dimer, platelet count, C-reactive protein (CRP), troponin, and international normalized ratio (INR) levels were recorded on the 1st, 5th, and 10th days of hospitalization in order to investigate the possible correlation of laboratory parameter changes with in-hospital events. A total of 161 non-survivors patients with COVID-19 were included in the study.&nbsp; The median age was 69.8±10.9 years, and 95 (59%) of the population were male. Lung-related complications were the most common in-hospital complications. Patients with COVID-19 had in-hospital complications such as major bleeding (39%), hemoptysis (14%), disseminated intravascular coagulation (13%), liver failure (21%), ARDS (85%), acute kidney injury (40%), and myocardial injury (70%). A multiple logistics regression analysis determined that age, hypertension, diabetes mellitus, use of acetylsalicylic acid (ASA) or low molecular weight heparin (LMWH), hemoglobin, D-dimer, INR, and acute kidney injury were independent predictors of major bleeding. Our results showed that a high proportion of COVID-19 non-survivors suffered from major bleeding complications.</span></p> Gokhan Alici Hasan Ali Barman Ramazan Asoglu Adem Atici Atike Nazli Akciger Omer Sit Omer Dogan Yucel Yavuz Songul Borahan Omer Genc Baris Gungor Copyright (c) 2021 Gokhan Alici, Hasan Ali Barman, Ramazan Asoglu, Adem Atici, Atike Nazli Akciger, Omer Sit, Omer Dogan, Yucel Yavuz, Songul Borahan, Omer Genc, Baris Gungor 2021-11-22 2021-11-22 21 6 10.17305/bjbms.2021.6577 Comparison of confirmed and probable COVID-19 patients in the intensive care unit during the normalization period <p><span style="font-weight: 400;">The decrease in social distance together with the normalization period as of June 1, 2020 in our country caused an increase in the number of COVID 19 patients. Our aim was to compare the demographic features, clinical courses and outcomes of confirmed and probable coronavirus disease 2019 (COVID-19) patients admitted to our intensive care unit (ICU) during the normalization period. Critically ill 128 COVID-19 patients between June 1 - December 2, 2020 were analyzed retrospectively. The mean age was 69.7±15.5y (61.7% male). Sixty-one patients (47.7%) were confirmed. Dyspnea (75.0%) was the most common symptom and hypertension (71.1%) was the most common comorbidity. The mean Acute Physiology and Chronic Health Evaluation System (APACHE II) score; Glasgow Coma Score (GCS); Sequential Organ Failure Assessment (SOFA) scores on&nbsp;ICU admission were&nbsp;17.4 ± 8.2, 12.3 ± 3.9&nbsp;and&nbsp;5.9 ± 3.4, respectively. 101 patients (78.1%) received low flow oxygen, 48 had high flow oxygen therapy (37.5%) and 59 (46.1%) had invasive mechanical ventilation. 53 patients (41.4%) had vasopressor therapy and 30 (23.4%) patients had renal replacement therapy (RRT) due to acute kidney injury (AKI). Confirmed patients were more tachypneic (p=0.005) and more hypoxemic than probable patients (p&lt;0.001). Acute respiratory distress syndrome (ARDS) and AKI were more common in confirmed patients than probable (both p&lt;0.001). Confirmed patients had higher values of hemoglobin, C- reactive protein, fibrinogen, D-dimer than probables (respectively, p=0.028, 0.006, 0.000, 0.019). The overall mortality was higher in confirmed patients (p=0.209, 52.6% vs 47.4%). Complications are more common among confirmed COVID-19 patients admitted to ICU. The mortality rate of confirmed COVID-19 patients admitted to the ICU was found to be higher than probable patients. Mortality of confirmed cases were higher than prediction of APACHE-II scoring system.</span></p> Fatma İrem Yeşiler Mesher Çapras Emre Kandemir Helin Şahintürk Ender Gedik Pınar Zeyneloğlu Copyright (c) 2021 Fatma İrem Yeşiler, Mesher Çapras, Emre Kandemir, Helin Şahintürk, Ender Gedik, Pınar Zeyneloğlu 2021-11-22 2021-11-22 21 6 10.17305/bjbms.2021.6657 A novel ferroptosis-related gene signature can predict prognosis and influence immune microenvironment in acute myeloid leukemia <p><span style="font-weight: 400;">Acute myeloid leukemia (AML) is a highly heterogeneous hematopoietic malignancy that strongly correlates with poor clinical outcomes. Ferroptosis is an iron-dependent, non-apoptotic form of regulated cell death which plays an important role in various human cancers. Nevertheless, the prognostic significance and functions of ferroptosis-related genes (FRGs) in AML have not received sufficient attention. The aim of this article was to evaluate the association between FRGs levels and AML prognosis using publicly available RNA-sequencing datasets. The univariate Cox regression analysis identified 20 FRGs that correlate with patient overall survival. The LASSO Cox regression model was used to construct a prognostic 12-gene risk model using a TCGA cohort, and internal and external validation proved the signature efficient. The 12-FRGs signature was then used to assign patients into high- and low-risk groups, with the former exhibiting markedly reduced overall survival, compared to the low-risk group. ROC curve analysis verified the predictive ability of the risk model. Functional analysis showed that immune status and drug sensitivity differed between the 2 risk groups. In summary, FRGs is a promising candidate biomarker and therapeutic target for AML.</span></p> Xianbo Huang De Zhou Xiujin Ye Jie Jin Copyright (c) 2021 Xianbo Huang, De Zhou, Xiujin Ye, Jie Jin 2021-11-16 2021-11-16 21 6 10.17305/bjbms.2021.6274 New insights into the pathological development of dyslipidemia in patients with hypothyroidism <p><span style="font-weight: 400;">According to the previous reports, hypothyroidism has been shown to be strongly correlated with increased circulating concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). Notably, thyroid hormones&nbsp; are confirmed to modulate the production, clearance, and transformation process of cholesterol within circulation of mammals. Moreover, emerging evidence suggests that the thyroid-stimulating hormone could also participate in modulating serum lipid metabolism independently of thyroid hormones, which further induces the pathological development of dyslipidemia. However, the underlying mechanism is still not fully elucidated. Recently, several research studies have demonstrated that the pathogenic progression of hypothyroidism-related dyslipidemia might be correlated with the decreased serum concentrations of thyroid hormones and the increased serum concentrations of thyroid-stimulating hormones. Thus, this indicates that hypothyroidism could induce dyslipidemia and its related cardio-metabolic disorder diseases. In addition, several newly identified modulatory biomarkers, such as proprotein convertase subtilisin/kexin type 9 (PCSK9), angiopoietin-like protein (ANGPTLs), and fibroblast growth factors (FGFs), might play an important role in the regulation of dyslipidemia induced by hypothyroidism. Furthermore, under the status of hypothyroidism, significantly dysfunctional HDL particles could also be observed. In the current review, we summarized the recent knowledge of the relationship between the development of hypothyroidism with dyslipidemia. We also discussed the updated understanding of the mechanisms whereby hypothyroidism induces the risk and the development of dyslipidemia and cardio-metabolic diseases.&nbsp;</span></p> Xin Su Xiang Chen Hua Peng Jingjin Song Bin Wang Xijie Wu Copyright (c) 2021 Xin Su, Xiang Chen, Hua Peng, Jingjin Song, Bin Wang, Xijie Wu 2021-11-15 2021-11-15 21 6 10.17305/bjbms.2021.6606