Bosnian journal of basic medical sciences最新文献

Circular RNA (circRNA) is a key regulator of tumor progression. However, the role of circFOXM1 in glioblastoma (GBM) progression is unclear. The aim of this study was to investigate the role of circFOXM1 in GBM progression. The expression levels of circFOXM1, miR-577, and E2F transcription factor 5 (E2F5) were examined by real-time quantitative polymerase chain reaction. Cell counting kit 8 assay, EdU staining, and transwell assay were used to detect cell proliferation, migration, and invasion. The levels of glutamine, glutamate, and α-ketoglutarate were determined to evaluate the glutaminolysis ability of cells. Protein expression was tested by Western blot analysis. Dual-luciferase reporter assay, RNA pull-down assay, and RNA immunoprecipitation assay were employed to verify the interaction between miR-577 and circFOXM1 or E2F5. Mice xenograft model for GBM was constructed to perform in vivo experiments. Our results showed that circFOXM1 was highly expressed in GBM tumor tissues and cells. Silencing of cir FOXM1 inhibited GBM cell proliferation, migration, invasion, glutaminolysis, as well as tumor growth. MiR-577 could be sponged by circFOXM1, and its inhibitor could reverse the suppressive effect of circFOXM1 downregulation on GBM progression. E2F5 was a target of miR-577, and the effect of its knockdown on GBM progression was consistent with that of circFOXM1 silencing. CircFOXM1 positively regulated E2F5 expression, while miR-577 negatively regulated E2F5 expression. In conclusion, our data confirmed that circFOXM1 could serve as a sponge of miR-577 to enhance the progression of GBM by targeting E2F5, which revealed that circFOXM1 might be a biomarker for GBM treatment.

The combination of hemoglobin, albumin, lymphocyte, and platelet (HALP) score has been confirmed as an important risk biomarker in several cancers. Hence, we aimed at evaluating the prognostic value of the HALP score in patients with non-metastatic upper tract urothelial carcinoma (UTUC). We retrospectively enrolled 533 of the 640 patients from two centers (315 and 325 patients, respectively) who underwent radical nephroureterectomy (RNU) for UTUC in this study. The cutoff value of HALP was determined using the Youden index by performing receiver operating characteristic (ROC) curve analysis. The relationship between postoperative survival outcomes and preoperative HALP level was assessed using Kaplan-Meier analysis and Cox regression analysis. As a result, the cutoff value of HALP was 28.67 and patients were then divided into HALP<28.67 group and HALP≥28.67 group. Kaplan-Meier analysis and log-rank test revealed that HALP was significantly associated with overall survival (OS) (P<0.001) and progression-free survival (PFS) (P<0.001). Multivariate analysis demonstrated that lower HALP score was an independent risk factor for OS (HR=1.54, 95%CI, 1.14-2.01, P=0.006) and PFS (HR=1.44, 95%CI, 1.07-1.93, P=0.020). Nomograms of OS and PFS incorporated with HALP score were more accurate in predicting prognosis than without. In the subgroup analysis, the HALP score could also stratify patients with respect to survival under different pathologic T stages. Therefore, pretreatment HALP score was an independent prognostic factor of OS and PFS in UTUC patients undergoing RNU.

Preterm births account for almost 1 million deaths globally. The objective of this study is to develop and evaluate a model that assists clinicians in assessing the risk of preterm birth, using fuzzy multicriteria analysis. The model allows experts to incorporate their intuition and judgment into the decision-making process and takes into consideration six (6) risk dimensions reflecting the socio-economic, behavioural and medical profile of pregnant women, thus adopting a holistic approach to risk assessment. Each risk dimension is further analysed and measured in terms of risk factors associated with it. Data was collected from a selected group of 35 experts, each one with more than 20 years of obstetric experience. The model criteria were selected after a thorough literature analysis, so as to ensure a holistic approach to risk assessment. The criteria were reviewed by the experts and the model structure was finalised. The fuzzy analytic hierarchy method was applied to calculate the relative importance of each criterion and subsequent use of the model in assessing and ranking pregnant women by their preterm risk. The proposed model utilises fuzzy logic and multicriteria analysis. It addresses the multifactorial nature of decision making when assessing the preterm birth risk. It also incorporates the obstetricians' intuitive judgement during risk assessment and it can be used to classify cases based upon their risk level. Additionally, it can be applied to evaluate the risk of individual cases in a personalised manner. The proposed model is compared and validated for its predictive value against judgments made by experts.

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 (ARG1, DEFA4, HP, MMP8, MMP9, MPO, OLFM4, PGLYRP1) 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 TPM2 and GZMB 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.

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 died 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.  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.

Testicular damage and testosterone secretion disorder are associated with diabetes mellitus. Quercetin,  a common flavonoid, has antioxidant, anti-cancer,  and blood sugar lowering effects. Therefore, this study aims to investigate the effect of quercetin on the reproductive system of male rats with diabetes in vivo and in vitro and elucidate its mechanism. Streptozotocin (STZ)  induction was used to establish a diabetes model in forty male Sprague Dawley (SD) rats, which were subsequently administered with 20 or 50 mg/kg of quercetin. Leydig cells of rat testes were treated by high glucose (HG) followed by 5 or 10 μM quercetin. Two doses of quercetin increased rat body weight and testicular weight, decreased blood glucose,and inhibited oxidative stress. RT-qPCR and Western blotting revealed that quercetin alleviated STZ-induced testicular damage and promoted testosterone synthesis. Both doses of quercetin reduced ROS and MDA levels, and increased SOD level in HG-treated cells. Both, in vivo and in vitro results confirmed that a high dose of quercetin was more effective. MiR-1306-5p was upregulated in testicular tissue of diabetic rats and HG-treated cells. 17β-hydroxysteroid dehydrogenase (HSD17B7) was a target of miR-1306-5p and HSD17B7 was downregulated in STZ-induced rat tissues and HG-treated cells. HSD17B7 overexpression reversed the increase of C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (Grp78) protein levels as well as eIF2α phosphorylation level and promotion of cell apoptosis caused by miR-1306-5p overexpression. Moreover, overexpression of HSD17B7 activated the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) axis in HG-treated cells. In conclusion, quercetin inhibits ER stress and improves testosterone secretion disorder through the miR-1306-5p/HSD17B7 axis in diabetic rats.

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 ICU admission were 17.4 ± 8.2, 12.3 ± 3.9 and 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<0.001). Acute respiratory distress syndrome (ARDS) and AKI were more common in confirmed patients than probable (both p<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.

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.