Bosnian Journal of Basic Medical Sciences https://www.bjbms.org/ojs/index.php/bjbms <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@bjbms.org (Faruk Skenderi) support@bjbms.org (Armin Sehovic) Wed, 25 Aug 2021 16:38:35 +0200 OJS 3.1.2.4 http://blogs.law.harvard.edu/tech/rss 60 Prevalence, clinical features and prognosis of malignant solid tumors in infants: a 14-year study https://www.bjbms.org/ojs/index.php/bjbms/article/view/5121 <p>The onset of malignant solid tumors in infants is insidious and difficult to diagnose on time. The purpose of our study is to provide a theoretical basis for clinical diagnosis by retrospective analysis of the data in the past 14 years. Here, we retrospectively collected the clinical data of infants aged 0-12 months with malignant solid tumors in Beijing Tongren Hospital Affiliated to Capital Medical University from May 2005 to May 2019. The epidemiology, clinical characteristics, treatments and prognosis were statistically analyzed. A total of 496 infants (294 males and 202 females) with malignant solid tumors were analyzed. The main period of onset was 1-11 months. The most common tumor was retinoblastoma (RB, 51.8%), followed by hepatoblastoma (HB, 26.6%), neuroblastoma (NB, 10.5%), rhabdomyosarcoma (RMS, 3.4%), malignant renal tumors (3.2%), infantile fibrosarcoma (IFS, 1.6%), malignant teratoma (1.2%), Ewing’s sarcoma (ES, 0.8%), medulloblastoma (MB, 0.4%) and inflammatory myofibroblastic tumor (IMT, 0.4%). The median follow-up time was 32 months (range 2-162 months). The 1-year, 3-year, and 5-year overall survival of all patients were 97.3%, 89.2%, and 81.1%, respectively, and event-free survival was 94.7%, 84.8%, and 75.8%, respectively. In conclusion, as a special group, malignant solid tumors in infants are complex, heterogeneous, and relatively rare. The prognosis of RB, HB, NB, RMS, malignant renal tumors, IFS, malignant teratoma, ES, MB, and IMT, were excellent duo to timely diagnosis and rational treatment.</p> Tian Zhi, Wei-Ling Zhang, Yi Zhang, Yi-Zhuo Wang, Dong-Sheng Huang Copyright (c) 2020 Tian Zhi, Wei-Ling Zhang, Yi Zhang, Yi-Zhuo Wang, Dong-Sheng Huang https://creativecommons.org/licenses/by/4.0 https://www.bjbms.org/ojs/index.php/bjbms/article/view/5121 Fri, 01 Oct 2021 00:00:00 +0200 Trends of incidence and prognosis of upper tract urothelial carcinoma https://www.bjbms.org/ojs/index.php/bjbms/article/view/5345 <p>The purpose of this study was to investigate trends in the incidence of upper tract urothelial carcinoma (UTUC) in patients and to establish a reliable and practical nomogram based on significant clinical factors to predict the overall survival (OS) and cancer-specific survival (CSS) of UTUC patients. The Surveillance, Epidemiology, and End Results (SEER) database was used to extract data on UTUC patients between 1988 and 2015. Incidence was calculated using Joinpoint regression software, and trends were quantified by annual percentage change (APC). A nomogram was constructed using R software to predict the OS and CSS probabilities for individual patients. From 1988 to 2015, the incidence of UTUC showed a downward trend (1988: 1.57/100,000 to 2015: 1.51/100,000; APC=-0.1). After stratification according to sex, age and primary site, we found that the incidences of UTUC in males, patients 70+ years old and the renal pelvis were higher than those in females, patients &lt;70 years old and ureter cancer patients. In the training cohort, the nomogram established based on multivariate Cox regression results showed better OS and CSS accuracy (OS: C-index=0.701, AUC=0.736; CSS: C-index=0.729, and AUC=0.688) than SEER stage. In addition, the calibration curves showed good consistency between the predicted and actual 3-, 5- and 10-year OS and CSS rates of the nomogram. In the past 30 years, the incidence of UTUC has shown a general downward trend, and the prognostic nomogram we established can provide a personalized risk assessment for the survival of UTUC patients.&nbsp;</p> Jianping Wu, Shuqiu Chen, Xiaoli Wu, Weipu Mao, Yali Wang, Bin Xu, Donghui Zheng, Ming Chen Copyright (c) 2020 Ming Chen, Jianping Wu, Shuqiu Chen, Xiaoli Wu, Weipu Mao, Yali Wang, Bin Xu, Donghui Zheng https://creativecommons.org/licenses/by/4.0 https://www.bjbms.org/ojs/index.php/bjbms/article/view/5345 Fri, 01 Oct 2021 00:00:00 +0200 Significance of chromogranin A and synaptophysin in medullary thyroid carcinoma https://www.bjbms.org/ojs/index.php/bjbms/article/view/5407 <p>Medullary thyroid carcinoma (MTC) is a relatively rare thyroid carcinoma of C-cell deviation and produces and secrete calcitonin (CT) and chromogranin A (CgA) into the blood. Thus, both CT and CgA are immunohistochemical and serum markers for MTCs. MTC occurs in both sporadic and inheritable cases and the hallmark of inheritable cases in multiple endocrine neoplasm 2 (NEN2) is MTC. MEN2 cases represent 30% of MTCs through germline RET protooncogene mutation and occur in younger ages involving bilateral thyroid lobes. Sporadic cases are 70% of cases of solitary tumor and occur in older ages. CgA and synaptophysin (SPY) are the two, most widely used and reliable immunohistochemical markers for neuroendocrine tumors including MTCs. This study aimed to detect different immunohistochemical staining patterns for CgA and SPY between non-symptomatic small, microscopic lesions and invading larger aggressive tumors in both MEA2 cases and sporadic cases. There was different CgA and SPY immunostaining in MEA2 cases where small tumors (≤ 0.3 cm) were lesser immunostained for CgA and SPY, despite strong staining for CT, compared to the larger (≥ 0.5cm) tumors, stronger immunostained for CgA. There was also different CgA and SPY immunohistochemical staining in sporadic cases between small lesion (≤ 0.5 cm) and larger tumors (≥ 1.0cm). One small sporadic tumor (0.5 x 0.3 cm) was strongly and weakly, patchy (about 10% of tumor tissue) stained for CgA and SPY, respectively, while larger sporadic tumors were diffusely, stronger stained for CgA and SPY. Therefore, stronger CgA and SPY immunostaining for larger tumors in both MEA2 and sporadic cases may be used as independent aggressive immunohistochemical markers for MTCs.</p> Tatsuo Tomita Copyright (c) 2020 Tatsuo Tomita https://creativecommons.org/licenses/by/4.0 https://www.bjbms.org/ojs/index.php/bjbms/article/view/5407 Fri, 01 Oct 2021 00:00:00 +0200 Development and validation of a SEER-based prognostic nomogram for cervical cancer patients below the age of 45 years https://www.bjbms.org/ojs/index.php/bjbms/article/view/5271 <p>In this study, we established a nomogram for the prognostic prediction of patients with early-onset cervical cancer (EOCC) for both overall survival (OS) and cancer-specific survival (CSS). The Surveillance, Epidemiology, and End Results (SEER) database was used to identify 10,079 patients diagnosed with EOCC between 2004 and 2015; these cases were then randomly divided into training and validation sets. The independent prognostic factors were identified in a retrospective study of 7,055 patients from the training set. A prognostic nomogram was developed using R software according to the results of multivariable Cox regression analysis. Furthermore, the model was externally validated using the data from the remaining 3,024 patients diagnosed at different times and enrolled in the SEER database. For the training set, the C-indexes for OS and CSS prediction were determined to be 0.831 (95 % confidence interval [CI]: 0.815–0.847) and 0.855 (95 % CI: 0.839–0.871), respectively. Receiver operating characteristic (ROC) analysis has revealed that the nomograms were a superior predictor compared with TNM stage and SEER stage. The areas under the curve (AUC) of the nomogram for OS and CSS prediction in the ROC analysis were 0.855 (95 % CI: 0.847–0.864) and 0.782 (95 % CI: 0.760–0.804), respectively. In addition, calibration curves indicated a perfect agreement between the nomogram-predicted and the actual 1-, 3-, and 5-year OS and CSS rates in the validation cohort. Thus, in this study, we established and validated a prognostic nomogram that provides an accurate prediction for 3-, 5-, and 10-year OS and CSS of EOCC patients. This will be useful for clinicians in guiding counseling and clinical trial design for cervical cancer patients.</p> Qunlong Liu, Wenxia Li, Ming Xie, Ming Yang, Mei Xu, Lei Yang, Bing Sheng, Yanna Peng, Li Gao Copyright (c) 2020 Qunlong Liu, Wenxia Li, Ming Xie, Ming Yang, Mei Xu, Lei Yang, Bing Sheng, Yanna Peng, Li Gao https://creativecommons.org/licenses/by/4.0 https://www.bjbms.org/ojs/index.php/bjbms/article/view/5271 Fri, 01 Oct 2021 00:00:00 +0200 Expression of NEDD9 and connexin-43 in neoplastic and stromal cells of gastric adenocarcinoma https://www.bjbms.org/ojs/index.php/bjbms/article/view/5379 <p>Gastric cancer is related to high mortality rates and advanced disease stage at the time of diagnosis. Its carcinogenesis is extensively studied and is associated with genetic and epigenetic changes, changed the interaction between tumor and adjacent stromal cells, and changes in the microenvironment molecule status. Neural precursor cell-expressed developmentally down-regulated 9 (NEDD9) affects different signaling proteins and pathways, apoptosis, adhesion, cell migration, and invasiveness. Connexin-43 (Cx43) also assists in intercellular communications and has several channel-independent functions. Aberrant expression of those two gap junction proteins plays an essential role in metastatic processes. Our scope was to detect the expression of Cx43 and NEDD9 in epithelial and stromal gastric cancer compartments and its relation to tumor progression and lymph node metastases. Cancer tissue from 53 cases of node-negative and 55 cases of node-positive primary gastric carcinoma patients was analyzed for Cx43 and NEDD9 expression by immunohistochemical assay, and the results were correlated with the remaining clinical and pathological findings and survival. In our cohort of patients with lymph node metastases, we detected higher expression of epithelial Cx43 in the primary tumor and stromal Cx43 expression correlated with both epithelial NEDD9 (rho = 0.453) and stromal NEDD9 (rho = 0.484). Higher epithelial Cx43 and NEDD9 expression were associated with higher mortality (HR 1.54, 95% CI 1.01-2.37, <em>p</em> = 0.048). Epithelial Cx43 expression, both epithelial and stromal NEDD9 expression, T and N status were all independently associated with shorter survival. In summary, our findings suggest that increased expression of both epithelial and stromal NEDD9 and epithelial Cx43 could potentially be used as prognostic gastric cancer biomarkers.</p> Ivan Lerotić, Petra Vuković, Davor Hrabar, Zvonimir Misir, Ivan Kruljac, Tajana Pavić, Jelena Forgač, Petra Ćaćić, Monika Ulamec Copyright (c) 2021 Ivan Lerotić, Petra Vuković, Davor Hrabar, Zvonimir Misir, Ivan Kruljac, Tajana Pavić, Jelena Forgač, Petra Čačić, Monika Ulamec https://creativecommons.org/licenses/by/4.0 https://www.bjbms.org/ojs/index.php/bjbms/article/view/5379 Fri, 01 Oct 2021 00:00:00 +0200 Development and validation of nomograms for predicting survival of elderly patients with stage I small-cell lung cancer https://www.bjbms.org/ojs/index.php/bjbms/article/view/5420 <p>There is a lack of predictive models to determine the prognosis of elderly patients diagnosed with Stage I small-cell lung cancer (SCLC). The purpose of&nbsp;this&nbsp;study&nbsp;was to establish a useful nomogram to predict cancer-specific survival (CSS) in the elderly patient population. Based on the Surveillance, Epidemiology, and End Results registry database, patients aged ≥ 65 years with pathological AJCC (American Joint Committee on Cancer) Stage I SCLC from 2004 to 2014 were identified. The CSS was evaluated by the Kaplan-Meier method. Patients were randomly split into training and validation sets. In the training cohort, univariate analysis and multivariate analysis using the Cox regression identified risk factors that affected CSS, and the results were utilized to construct a nomogram for prediction of the 1-, 3-, and 5-year CSS rates of elderly patients with Stage I SCLC. The&nbsp;effectiveness of the nomogram was validated internally and externally by the bootstrap method. The clinical practicability and accuracy of the nomogram were evaluated by the concordance index (C-index), calibration curve, receiver operating characteristic curve, and decision curve analysis. In total, we extracted 1,623 elderly patients with Stage I SCLC. The median CSS was 34 months, and the 5-year CSS was 41%. Multivariate analysis revealed that histologic type, tumor size, age, and AJCC Stage were significant predictors of CSS. A nomogram was constructed according to the results of multivariate COX analysis. The C-indices of the nomogram for training and validation sets were 0.68 and 0.62, indicating that the nomogram demonstrated a favorable level of discrimination. The calibration curves exhibited satisfactory agreement between the actual observation and nomogram prediction. The net benefit of the nomogram was better than the AJCC TNM staging. A practical nomogram to predict the CSS of elderly patients with Stage I SCLC is constructed. The predictive tool is helpful for patient counseling and treatment decision-making.</p> Yaji Yang, Shusen Sun, Yuwei Wang, Feng Xiong, Yin Xiao, Jing Huang Copyright (c) 2021 Yaji Yang, Shusen Sun, Yuwei Wang, Feng Xiong, Yin Xiao, Jing Huang https://creativecommons.org/licenses/by/4.0 https://www.bjbms.org/ojs/index.php/bjbms/article/view/5420 Fri, 01 Oct 2021 00:00:00 +0200 Sirtuin 1 rs7069102 polymorphism is associated with diabetic nephropathy in patients with type 2 diabetes mellitus https://www.bjbms.org/ojs/index.php/bjbms/article/view/5368 <p>The global prevalence for diabetes mellitus nearly doubled from 4.7% in 1980 to 8.5% in 2014. Sirtuin 1 (SIRT1) is an NAD+-dependent deacetylase that is expressed in a variety of tissues. It modifies proteins that participate in DNA repair, stress, and inflammatory response. The aim of the study was to investigate the relationship between SIRT1 rs7069102 polymorphism and diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM). In our retrospective association study, we included 724 Slovene (Caucasian) patients who have had T2DM for at least 10 years. We classified the participants into two groups, the first group was comprised of 301 patients with DN, and the second (control) group was comprised of 423 patients without DN. We analyzed the rs7069102 polymorphism using StepOne real-time polymerase chain reaction (PCR) System and TaqMan SNP Genotyping Assay. We found a statistically significant difference in the distribution of rs7069102 genotypes and alleles between the two groups. We used logistic regression analysis and adjusted for systolic pressure, arterial hypertension (AH), duration of AH, triglycerides, the value of HbA1c, carotid disease, diabetic foot, and diabetic retinopathy. Furthermore, we discovered that patients with the CC genotype are significantly more likely to develop DN according to both the codominant (odds ratio [OR] = 1.94; 95% confidence interval [CI] = 1.09-3.45; <em>p</em> = 0.02) and recessive (OR = 2.39; 95% CI = 1.12-5.08; <em>p</em> = 0.02) models of inheritance. We found a significant association between the SIRT1 rs7069102 polymorphism and DN in T2DM. We speculate that SIRT1 rs7069102 might be an interesting marker of DN.</p> Jernej Letonja, Matej Završnik, Jana Makuc, Maja Šeruga, Ana Peterlin, Ines Cilenšek, Danijel Petrovič Copyright (c) 2021 Jernej Letonja, Matej Završnik, Jana Makuc, Maja Šeruga, Ana Peterlin, Ines Cilenšek, Danijel Petrovič https://creativecommons.org/licenses/by/4.0 https://www.bjbms.org/ojs/index.php/bjbms/article/view/5368 Fri, 01 Oct 2021 00:00:00 +0200 Extreme lateral interbody fusion (XLIF) in a consecutive series of 72 patients https://www.bjbms.org/ojs/index.php/bjbms/article/view/5261 <p>Extreme lateral interbody fusion (XLIF) has become the standard of minimally invasive lumbar segmental scoliosis treatment. Our objective is to determine the safety and efficacy of XLIF in spinal canal stenosis (SCS) and spondylodiscitis (SD). Patients treated with XLIF in our department between 2012 and 2018 were retrospectively analyzed. Patient records with clinical and radiographical parameters were evaluated. The patient cohort consists of 40 male and 32 female patients with a median age of 66.6 years. Forty-five patients had an SCS and 27 patients SD. The mean follow-up was 23 months. One level XLIF was performed in 49 patients, 2 levels in 15, 3 levels in 7 patients and 4 levels in 1 patient. All but one patient received an additional dorsal stabilization. The pain was present in all patients with a mean Visual Analogue Scale (VAS) score of 8.8 vs. postoperative VAS of 2.8 (<em>p</em>&lt;0.05). Preoperative neurological deficits were found in 44 patients. Only 6 patients had a neurological deterioration, 45 patients improved, and 21 patients remained unchanged. One patient experienced a perioperative complication.&nbsp; Non-fusion occurred in 8 cases. There were no outcome differences regarding pain and radiological outcome between patients with SCS and SD as well as between patients with one level vs. multilevel surgery. Baseline characteristics and the radiological outcome did not differ between the two groups. Patients with SD had a higher rate of worsening of neurological deficits following surgery, a higher rate of non-fusion, and a longer hospital stay. Patients with spinal canal stenosis SCS had a longer surgery time and more frequent adjacent segment disease.</p> Mirza Pojskic, Benjamin Saβ, Benjamin Völlger, Christopher Nimsky, Barbara Carl Copyright (c) 2021 Mirza Pojskic, Benjamin Saβ, Benjamin Völlger, Christopher Nimsky, Barbara Carl https://creativecommons.org/licenses/by/4.0 https://www.bjbms.org/ojs/index.php/bjbms/article/view/5261 Fri, 01 Oct 2021 00:00:00 +0200 SARS-CoV-2 infection: Understanding the immune system abnormalities to get an adequate diagnosis https://www.bjbms.org/ojs/index.php/bjbms/article/view/5400 <p>COVID-19 is the current pandemic caused by the novel coronavirus, SARS-CoV-2, that emerged from China at the end of December 2019. The scientific community is making extraordinary efforts to understand the virus structure and the pathophysiology and immunological processes activated in the host, in order to identify biomarkers, diagnostic tools, treatments, and vaccines to decrease COVID-19 incidence and mortality. Various abnormalities have been noted during SARS-CoV-2 infection both in lymphoid and myeloid cells. Such abnormalities may disturb the immune system function and cause a massive inflammatory response that impairs tissue function. This review discusses the close relationship between the immune system abnormalities and the broad spectrum of clinical manifestations, including fibrosis, in the context of COVID-19 disease. Moreover, we described the current strategies for COVID-19 diagnosis, and we provide a summary of the most useful clinical laboratory parameters to identify severe COVID-19 patients.</p> Karen Medina-Quero, Omar Barreto-Rodriguez, Voltaire Mendez-Rodriguez, Anahí Sanchez-Moncivais, Ivette Buendia-Roldan, Leslie Chavez-Galan Copyright (c) 2021 Karen Medina-Quero, Omar Barreto-Rodriguez, Voltaire Mendez-Rodriguez, Anahí Sanchez-Moncivais, Ivette Buendia-Roldan, Leslie Chavez-Galan https://creativecommons.org/licenses/by/4.0 https://www.bjbms.org/ojs/index.php/bjbms/article/view/5400 Fri, 01 Oct 2021 00:00:00 +0200 Circ-RNF13, as an oncogene, regulates malignant progression of HBV-associated hepatocellular carcinoma cells and HBV infection through ceRNA pathway of circ-RNF13/miR-424-5p/TGIF2 https://www.bjbms.org/ojs/index.php/bjbms/article/view/5266 <p>Circular RNA RNF13 (circ-RNF13; ID: hsa_circ_0067717) is newly identified to be abnormally upregulated in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) patients. However, its role and mechanism remain to be further annotated. First of all, real-time quantitative PCR (RT-qPCR) was utilized to examine RNA expression, and circ-RNF13 was upregulated in HBV-infected human HCC tissues and HBV-expressing cells (Huh7-HBV and Hep3B-HBV), accompanied with TGFβ-induced factor homeobox 2 (TGIF2) upregulation and microRNA (miR)-424-5p downregulation. Loss-of-functional experiments were performed using MTS assay, colony formation assay, flow cytometry, enzyme-linked immunosorbent assay, transwell assay, and xenograft tumor model. As a result, blocking circ-RNF13 enhanced the apoptosis rate of Huh7-HBV and Hep3B-HBV cells, but inhibited cell proliferation, colony formation, migration, and invasion <em>in vitro</em>, along with suppressed tumor growth&nbsp;<em>in vivo</em>. Besides, RT-qPCR data showed that HBV DNA copies and levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were diminished by circ-RNF13 knockdown in Huh7-HBV and Hep3B-HBV cells. Mechanistically, circ-RNF13 and TGIF2 could directly interacting with miR-424-5p according to dual-luciferase reporter assay, suggesting that circ-RNF13 and TGIF2 served as competing endogenous RNAs (ceRNAs) for miR-424-5p. Functionally, overexpressing miR-424-5p mimicked and silencing miR-424-5p counteracted the effects of circ-RNF13 depletion in HBV-expressing HCC cells<em>&nbsp;in vitro</em>; TGIF2 restoration partially abrogated the role of miR-424-5p upregulation. In conclusion, circ-RNF13 might sponge miR-424-5p to suppress HBV-associated HCC cells malignant progression and HBV infection by regulating TGIF2, providing a novel insight into the occurrence and treatment of HBV-associated HCC.&nbsp;</p> Yan Chen, Shuhua Li, Yinbin Wei, Zhihong Xu, Xiongfei Wu Copyright (c) 2021 Yan Chen, Shuhua Li, Yinbin Wei, Zhihong Xu, Xiongfei Wu https://creativecommons.org/licenses/by/4.0 https://www.bjbms.org/ojs/index.php/bjbms/article/view/5266 Fri, 01 Oct 2021 00:00:00 +0200 Insight into the emerging role of SARS-CoV-2 nonstructural and accessory proteins in modulation of multiple mechanisms of host innate defense https://www.bjbms.org/ojs/index.php/bjbms/article/view/5543 <p>Coronavirus disease-19 (COVID-19) is an extremely infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has become a major global health concern. The induction of a coordinated immune response is crucial to the elimination of any pathogenic infection. However, SARS-CoV-2 can modulate the host immune system to favor viral adaptation and persistence within the host. The virus can counteract type I interferon (IFN-I) production, attenuating IFN-I signaling pathway activation and disrupting antigen presentation. Simultaneously, SARS-CoV-2 infection can enhance apoptosis and the production of inflammatory mediators, which ultimately results in increased disease severity. SARS-CoV-2 produces an array of effector molecules, including nonstructural proteins (NSPs) and open-reading frames (ORFs) accessory proteins. We describe the complex molecular interplay of SARS-CoV-2 NSPs and accessory proteins with the host’s signaling mediating immune evasion in the current review. In addition, the crucial role played by immunomodulation therapy to address immune evasion is discussed. Thus, the current review can provide new directions for the development of vaccines and specific therapies.</p> Abualgasim Elgaili Abdalla , Jianping Xie, Kashaf Junaid, Sonia Younas, Tilal Elsaman, Khalid Omer Abdalla Abosalif, Ayman Ali Mohammed Alameen, Mahjoob Osman Mahjoob, Mohammed Yagoub Mohammed Elamir, Hasan Ejaz Copyright (c) 2021 Abualgasim Elgaili Abdalla , Jianping Xie, Kashaf Junaid, Sonia Younas, Tilal Elsaman, Khalid Omer Abdalla Abosalif, Ayman Ali Mohammed Alameen, Mahjoob Osman Mahjoob, Mohammed Yagoub Mohammed Elamir, Hasan Ejaz https://creativecommons.org/licenses/by/4.0 https://www.bjbms.org/ojs/index.php/bjbms/article/view/5543 Fri, 01 Oct 2021 00:00:00 +0200 Development and validation of a ferroptosis-related lncRNAs prognosis signature in colon cancer https://www.bjbms.org/ojs/index.php/bjbms/article/view/5617 <p>Ferroptosis is a form of iron-dependent programmed cell death. Regulation of ferroptosis in tumor cells is a novel treatment modality. The present study aimed to investigate ferroptosis-related long non-coding RNAs (lncRNAs) and construct a prognostic model for colon adenocarcinoma (COAD). RNA- sequencing data and ferroptosis-related genes were obtained from The Cancer Genome Atlas database and FerrDb database. COAD patients were randomly assigned to training- and validation groups. The Least Absolute Shrinkage and Selection Operator regression and Cox regression model were used to determine and develop a predictive model. The model was corroborated using the validation group and the entire group. In total, 259 ferroptosis-related genes and 905 ferroptosis-related LncRNAs were obtained. Cox model revealed and constructed seven ferroptosis-related LncRNAs signature (LINC01503, AC004687.1, AC010973.2, AP001189.3, ARRDC1-AS1, OIP5-AS1, and NCK1-DT). Patients were assigned into two groups according to the median risk score. Kaplan–Meier survival curves showed that overall survival between high- and low-risk groups was statistically significant (P&lt;0.01). Cox multivariate analysis seven ferroptosis-related LncRNAs signature was an independent risk factor for COAD outcomes (P&lt;0.05). The relationship between seven ferroptosis-related LncRNAs and clinicopathological features was also examined. The principal component analysis showed a difference between high- and low-risk groups intuitively. With the aid of gene set enrichment analysis, the underlying mechanisms of seven ferroptosis-related LncRNAs were uncovered, including the MAPK signaling pathway, mTOR signaling pathway, and glutathione metabolism pathway. Finally, we established and validated seven ferroptosis-related lncRNAs signature for COAD patients to predict survival. These results may provide meaningful targets for future study.</p> Hua-jun Cai, Zhi-cheng Zhuang, Yong Wu, Yi-yi Zhang, Xing Liu, Jin-fu Zhuang, Yuan-feng Yang, Yuan Gao, Bin Chen, Guo-xian Guan Copyright (c) 2021 Hua-jun Cai, Zhi-cheng Zhuang, Yong Wu, Yi-yi Zhang, Xing Liu, Jin-fu Zhuang, Yuan-feng Yang, Yuan Gao, Bin Chen, Guo-xian Guan https://creativecommons.org/licenses/by/4.0 https://www.bjbms.org/ojs/index.php/bjbms/article/view/5617 Fri, 01 Oct 2021 00:00:00 +0200 The role of WDR76 protein in human diseases https://www.bjbms.org/ojs/index.php/bjbms/article/view/5506 <p>The WD40 repeat (WDR) domain is one of the most abundant protein interaction domains in the human proteome. More than 360 protein interaction domains have been annotated thus far. The WDR domains mediate interactions with peptide regions of important interaction partners in a variety of biological processes. Proteins with the WDR domain which typically contains a seven-bladed β propeller, are continuously being discovered. They represent a large class of proteins that are likely to play important roles. WD40 repeat domain-containing protein 76 (WDR76) is a member of WDR domain-containing proteins. Although it remains poorly understood, it is potentially involved in DNA damage repair, apoptosis, cell cycle progression, and gene expression regulation. Ongoing research on WDR76 is increasing the knowledge regarding its basic functions and role in different pathophysiological. The study of WDR76 is challenging due to the complexity of its interactions with its partners. In the present review, we summarized the current knowledge regarding WDR76, its physiological functions, the close relationship with human diseases, and potential opportunities for target therapy.</p> Jie Yang, Fei Wang, Baoan Chen Copyright (c) 2021 Jie Yang, Fei Wang, Baoan Chen https://creativecommons.org/licenses/by/4.0 https://www.bjbms.org/ojs/index.php/bjbms/article/view/5506 Fri, 01 Oct 2021 00:00:00 +0200 Quantitative detection of circulating MT-ND1 as a potential biomarker for colorectal cancer https://www.bjbms.org/ojs/index.php/bjbms/article/view/5576 <p>Liquid biopsy represents a diagnostic and monitoring tool and the circulating cell-free mitochondrial DNA (mtDNA) plays a vital role in tumor diagnosis and dynamic assessment. Colorectal cancer (CRC) is one of the most common fatal cancers worldwide. Mitochondrially encoded NADH dehydrogenase subunit 1 (MT-ND1) encodes the biggest subunit of respiratory complex I of mtDNA, and mutations in the MT-ND1 are common in CRC. We sought to determine if mutations in circulating MT-ND1 could be a potential biomarker for colorectal cancer. In this study, twenty-two CRC patients at Zhujiang Hospital were included. We mainly used droplet digital PCR to determine the mutation status of MT-ND1, combined with clinical data. In the experiment<em> in vivo</em>, cell-free mtDNA generally presented high concordance with tumor tissues. By quantitative PCR, the MT-ND1 content of plasma in CRC patients was significantly higher than that in healthy individuals (58.01 vs. 0.64, <em>p</em>=0.027). The detection of circulating MT-ND1 content and variants (m.3606 A&gt;G, m.3970 C&gt;T, m.4071 C&gt;T, m.4086 C&gt;T) in cfDNA showed a good correlation with predicted tumor response and progression to chemotherapy. In conclusion, the content and variants of circulating MT-ND1 may become a versatile tool for the diagnosis and monitoring of colorectal cancer.</p> Yichun Xu, Jiajing Zhou, Qing Yuan, Jun Su, Qian Li, Xiaoliang Lu, Liwen Zhang, Zhai Cai, Junsong Han Copyright (c) 2021 Yichun Xu, Jiajing Zhou, Qing Yuan, Jun Su, Qian Li, Xiaoliang Lu, Liwen Zhang, Zhai Cai, Junsong Han https://creativecommons.org/licenses/by/4.0 https://www.bjbms.org/ojs/index.php/bjbms/article/view/5576 Fri, 01 Oct 2021 00:00:00 +0200 Plasma exosome-derived fragile-site associated tumor suppressor is a powerful predictor of prognosis in patients with ovarian cancer https://www.bjbms.org/ojs/index.php/bjbms/article/view/6404 <p><strong><em>Objective</em></strong><strong>: </strong>To investigate the levels of plasma exosome-derived fragile-site associated tumor suppressor (FATS) and evaluate its predictive ability in ovarian cancer (OC) patients.</p> <p><strong><em>Patients and Methods</em></strong><strong>:</strong> Exosome-rich fractions were isolated from the plasma of enrolled 90 patients with OC. The levels of plasma exosome-derived FATS were detected with ELISA.</p> <p><strong><em>Results</em></strong><strong>:</strong> The levels of exosome-derived FATS in OC patient were significantly lower than in healthy controls (<em>P</em> &lt; 0.001). The levels of plasma exosome-derived FATS were obviously higher in OC patients with low grade (1/2), FIGO stages I/II than high grade (3/4), stages III/ IV disease (<em>P </em>= 0.003;<em> P </em>&lt; 0.001). The levels of plasma exosome-derived FATS were significantly higher in OC patients with no lymph node metastasis, no ascites than those with lymph node metastasis, ascites (both <em>P</em> &lt; 0.001). The levels of plasma exosome-derived FATS were obviously higher in OC patients with CA-125 less than 35U/ml than more than 35U/ml (<em>P </em>&lt; 0.001). Among all enrolled OC patients, both 5-DFS and 5-OS were shorter in patients who had low plasma exosome-derived FATS levels than that high levels (both <em>P</em> &lt; 0.001). The AUROC of plasma exosome-derived FATS were 0.85(95% CI: 0.76-0.91) for 5-DFS, 0.91(95% CI: 0.83-0.96) for 5-OS prediction in patients with OC, respectively.</p> <p><strong><em>Conclusions</em></strong><strong>: </strong>Plasma exosome-derived FATS levels in OC patient were significantly down-regulated. Low levels of plasma exosome-derived FATS had close relationship with FIGO stages I/II, low grade, ascites, higher levels of CA-125, lymph node metastasis and prognosis of OC patients. Our findings may provide a new strategy in treating OC.</p> Renjing Ju, Xiaochun Chen, Shiliang Zhang, Bin Liu, Hao Pei, Fan Tu, Jun Liu, Hao Yu Copyright (c) 2021 Renjing Ju, Xiaochun Chen, Shiliang Zhang, Bin Liu, Hao Pei, Fan Tu, Jun Liu, Hao Yu https://creativecommons.org/licenses/by/4.0 https://www.bjbms.org/ojs/index.php/bjbms/article/view/6404 Tue, 07 Sep 2021 19:39:28 +0200 Call for emergency action to limit global temperature increases, restore biodiversity, and protect health https://www.bjbms.org/ojs/index.php/bjbms/article/view/6411 <p><span style="font-weight: 400;">The UN General Assembly in September 2021 will bring countries together at a critical time for marshalling collective action to tackle the global environmental crisis. They will meet again at the biodiversity summit in Kunming, China, and the climate conference (COP26) in Glasgow, UK. Ahead of these pivotal meetings, we—the editors of health journals worldwide—call for urgent action to keep average global temperature increases below 1.5°C, halt the destruction of nature, and protect health.</span></p> <p>Read more in&nbsp; <strong><a href="https://www.bjbms.org/ojs/index.php/bjbms/article/view/6411/2375">PDF</a>.</strong></p> Lukoye Atwoli, Abdullah H. Baqui, Thomas Benfield, Raffaella Bosurgi, Fiona Godlee, Stephen Hancocks, Richard Horton, Laurie Laybourn-Langton, Carlos Augusto Monteiro, Ian Norman, Kirsten Patrick, Nigel Praities, Marcel Olde Rikkert, Eric J. Rubin, Peush Sahni, Richard Smith, Nicholas J Talley, Sue Turale, Damián Vázquez Copyright (c) 2021 Lukoye Atwoli, Abdullah H. Baqui, Thomas Benfield, Raffaella Bosurgi, Fiona Godlee, Stephen Hancocks, Richard Horton, Laurie Laurie Laybourn-Langton, Carlos Augusto Monteiro, Ian Norman, Kirsten Patrick, Nigel Praities, Marcel Olde Rikkert, Eric J. Rubin, Peush Sahni, Richard Smith, Nick Talley, Sue Turale, Damián Vázquez https://creativecommons.org/licenses/by/4.0 https://www.bjbms.org/ojs/index.php/bjbms/article/view/6411 Mon, 06 Sep 2021 08:45:51 +0200 Poorly differentiated clusters and tumor budding are important prognostic factors in colorectal carcinomas https://www.bjbms.org/ojs/index.php/bjbms/article/view/6110 <p><span style="font-weight: 400;">The aim of our study was to assess the prognostic value of the two new grading systems based on the quantification of tumor budding - TB (GBd) and poorly differentiated clusters - PDCs (PDCs-G) in colorectal carcinomas (CRC). We performed a retrospective study on 71 CRC patients who underwent surgery at the Emergency County Hospital, Timișoara. CRC cases were classified based on haematoxylin-eosin slides, using the conventional grading system, GBd and PDCs-G, respectively. We used two-tier and three-tier grading schemes for each system. Subsequently,&nbsp; we evaluated&nbsp; associations with other prognostic factors in CRC. Based on the three-tier GBd (GBd-3t)&nbsp; most cases (34/69, 49.27%) were classified as G3Bd-3t, while based on the conventional grading system, the majority of the cases (55/69, 79.71%) were considered G2. On the other hand, based on the three-tier PDCs-G system (PDCs-G-3t), most cases (31/69, 44.93%) were PDCs-G2-3t. We also noted a more significant association of GBd-3t with other prognostic parameters analyzed, as compared to the conventional grading system. Nodal status, tumor stage, and lymphovascular invasion were strongly correlated with GBd-3t (p=0.0001). Furthermore, we noted that PDCs-G-3t correlated more significantly than the conventional grading system with nodal status (p&lt;0.0001), tumor stage (p=0.0003), lymphovascular invasion (p&lt;0.0001), perineural invasion (p=0.005) and the tumor border configuration (p&lt;0.0001).&nbsp;</span></p> <p><span style="font-weight: 400;">High GBd and PDCs-G grades correlate directly with other negative prognostic factors in CRC.Thus, these new parameters/classification methods could be used as additional tools for risk stratification in patients with CRC.</span></p> <p><br><br></p> Aura Jurescu, Adrian Văduva, Adelina Gheju Copyright (c) 2021 Aura Jurescu, Adrian Văduva, Adelina Gheju https://creativecommons.org/licenses/by/4.0 https://www.bjbms.org/ojs/index.php/bjbms/article/view/6110 Fri, 03 Sep 2021 20:13:52 +0200 Altered molecular pathways and prognostic markers in active systemic juvenile idiopathic arthritis: integrated bioinformatic analysis https://www.bjbms.org/ojs/index.php/bjbms/article/view/6016 <p><span style="font-weight: 400;">Systemic juvenile idiopathic arthritis (SJIA) is a severe childhood-onset inflammatory disease characterized by arthritis accompanied by systemic auto-inflammation and extra-articular symptoms. While recent advances have unraveled a range of risk factors, the pathomechanisms involved in SJIA and potential prognostic markers for treatment success remain partly unknown. In this study, we included 70 active SJIA and 55 healthy control patients from the National Center for Biotechnology Information to analyze for differentially expressed genes (DEGs) using R. Functional enrichment analysis, protein-protein interaction (PPI), and gene module construction were performed for DEGs and hub gene set. We additionally examined immune system cell composition with CIBERSORT and predicted prognostic markers and potential treatment drugs for SJIA. In total, 94 upregulated and 24 downregulated DEGs were identified. Two specific modules of interest and eight hub genes (</span><em><span style="font-weight: 400;">ARG1</span></em><span style="font-weight: 400;">, </span><em><span style="font-weight: 400;">DEFA4</span></em><span style="font-weight: 400;">, </span><em><span style="font-weight: 400;">HP</span></em><span style="font-weight: 400;">, </span><em><span style="font-weight: 400;">MMP8</span></em><span style="font-weight: 400;">,</span><em><span style="font-weight: 400;"> MMP9</span></em><span style="font-weight: 400;">,</span><em><span style="font-weight: 400;"> MPO</span></em><span style="font-weight: 400;">,</span><em><span style="font-weight: 400;"> OLFM4</span></em><span style="font-weight: 400;">,</span><em><span style="font-weight: 400;"> PGLYRP1</span></em><span style="font-weight: 400;">) were screened out. Functional enrichment analysis suggested that complex neutrophil-related functions play a decisive role in the disease pathogenesis. CIBERSORT indicated neutrophils, M0 macrophages, CD8+ T cells, and naïve B cells to be relevant drivers of disease progression. Additionally, we identified </span><em><span style="font-weight: 400;">TPM2</span></em><span style="font-weight: 400;"> and </span><em><span style="font-weight: 400;">GZMB</span></em><span style="font-weight: 400;"> as potential prognostic markers for treatment response to canakinumab. Moreover, sulindac sulfide, (-)-catechin, and phenanthridinone were identified as promising treatment agents. This study provides a new insight into molecular and cellular pathogenesis of active SJIA and highlights potential targets for further research.</span></p> Yi Ren, Hannah Labinsky, Andriko Palmowski, Henrik Bäcker, Michael Müller, Arne Kienzle Copyright (c) 2021 Yi Ren, Hannah Labinsky, Andriko Palmowski, Henrik Bäcker, Michael Müller, Arne Kienzle https://creativecommons.org/licenses/by/4.0 https://www.bjbms.org/ojs/index.php/bjbms/article/view/6016 Fri, 03 Sep 2021 14:50:43 +0200 Selection of optimal therapeutic modality for early-stage extranodal natural killer/T-cell lymphoma patients under the guidance of single-nucleotide polymorphism signature https://www.bjbms.org/ojs/index.php/bjbms/article/view/6419 <p><span style="font-weight: 400;">The</span> <span style="font-weight: 400;">therapeutic modalities of early-stage and advanced extranodal natural killer/T-cell lymphoma (NKTCL) patients are completely different. The former is mainly radiotherapy with or without chemotherapy, while the latter relies on chemotherapy-based systemic treatment.</span><span style="font-weight: 400;">&nbsp;According to Ann Arbor staging system, approximately 70% of the NKTCL patients are classified as early-stage cases who are promising to be cured.</span><span style="font-weight: 400;">Considering NKTCL is sensitive to radiation but may be resistant to chemotherapy, the radiotherapy is considered to be the most important treatment for some early-stage patients with a satisfactory local control rate and could be used alone.</span><span style="font-weight: 400;"> However, systemic recurrence after radiotherapy in a portion of NKTCL patients seriously affects their long-term survival, and the first-line treatment combined with radiotherapy and chemotherapy is considered necessary. Therefore, the use of radiotherapy alone in early-stage NKTCL is still a controversial issue.</span></p> <p><span style="font-weight: 400;">Read more in <a href="https://dx.doi.org/10.17305/bjbms.2021.6419">PDF</a>.</span></p> Zhe-Sheng Chen, Dong-Hua Yang Copyright (c) 2021 Zhe-Sheng Chen, Dong-Hua Yang https://creativecommons.org/licenses/by/4.0 https://www.bjbms.org/ojs/index.php/bjbms/article/view/6419 Tue, 24 Aug 2021 18:55:37 +0200 Six RNA binding proteins (RBPs) related prognostic model predicts overall survival for clear cell renal cell carcinoma and it is associated with immune infiltration https://www.bjbms.org/ojs/index.php/bjbms/article/view/6097 <p><span style="font-weight: 400;">The aim of this article was to construct an accurate prognostic model by using RNA-binding proteins (RBPs) to predict overall survival (OS) for patients with clear cell renal cell carcinoma (ccRCC) as well as to reveal its associations with immune infiltration.</span> <span style="font-weight: 400;">Expression profiles based on RNA-binding proteins (RBPs) and&nbsp; clinical follow-up parameters were obtained from the Cancer Genome Atlas (TCGA) and the ArrayExpress databases. Through univariate COX and LASSO regression analyses, the RBPs based signature was developed. A total of six RBPs (CLK2, IGF2BP2, RNASE2, EZH2, PABPC1L, RPL22L1) were eventually used to establish a prognostic signature. Based on this signature, ccRCC patients were classified into high-risk and low-risk subgroups and significant OS was obtained in both the internal and external datasets (</span><em><span style="font-weight: 400;">p</span></em><span style="font-weight: 400;">&lt;0.05). AUCs of its ROC curve were all above 0.70 and this signature was an independent prognostic factor of OS for ccRCC (</span><em><span style="font-weight: 400;">p</span></em><span style="font-weight: 400;">&lt;0.05). Nomograms were also constructed to visualize the relationships among individual predictors and 1-, 3- and 5-year OS for ccRCC. Furthermore, the established RBPs based signature was strongly related to critical clinicopathologic characteristics such as grade (</span><em><span style="font-weight: 400;">p</span></em><span style="font-weight: 400;">=8.921e−12), stage (</span><em><span style="font-weight: 400;">p</span></em><span style="font-weight: 400;">=1.421e−11), M (</span><em><span style="font-weight: 400;">p</span></em><span style="font-weight: 400;">=1.662e−05), and T stage (</span><em><span style="font-weight: 400;">p</span></em><span style="font-weight: 400;">=7.907e−10). Moreover, 12 kinds of tumor-infiltrating immune cells were significantly linked to high-risk and low-risk groups classified by our constructed model (all </span><em><span style="font-weight: 400;">p</span></em><span style="font-weight: 400;">&lt;0.05).</span> <span style="font-weight: 400;">Our study successfully identified six RBPs as a robust prognostic signature in ccRCC by both external and internal verification. Besides, our established model displayed significant associations with immune infiltration. In addition to original clinical parameters, our findings may further help clinicians in predicting patients’ survival status and creating individualized treatment plans.</span></p> Qianwei Xing, Jiaochen Luan, Shouyong Liu, Limin Ma, Yi Wang Copyright (c) 2021 Qianwei Xing, Jiaochen Luan, Shouyong Liu, Limin Ma, Yi Wang https://creativecommons.org/licenses/by/4.0 https://www.bjbms.org/ojs/index.php/bjbms/article/view/6097 Sun, 22 Aug 2021 20:16:14 +0200