MicroRNAs (miRNAs) have an important role in the regulation of tumor development and metastasis. In this study, we investigated the clinical and prognostic value as well as biological function of miR-466 in colorectal cancer (CRC). Tumor and adjacent healthy tissues were obtained from 100 patients diagnosed with CRC. miR-466 expression was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). mRNA and protein levels of cyclin D-1, apoptosis regulator BAX (BAX), and matrix metalloproteinase-2 (MMP-2) were analyzed by qRT-PCR and Western blot, respectively, in SW-620 CRC cells transfected with miR-466 mimics or negative control miRNA. Effects of miR-466 on SW-620 cell proliferation, cell cycle and apoptosis, and invasion were investigated using CCK-8 assay, flow cytometry and Transwell assay, respectively. miR-466 expression was significantly downregulated in tumor tissues compared to matched adjacent non-tumor tissues. Low expression of miR-466 was significantly correlated with the tumor size, Tumor Node Metastasis stage, lymph node metastasis, and distant metastasis. The overall survival of CRC patients with low miR-466 expression was significantly shorter compared to high-miR-466 expression group (log-rank test: p = 0.0103). Multivariate analysis revealed that low miR-466 expression was associated with poor prognosis in CRC patients. The ectopic expression of miR-466 suppressed cell proliferation and migration/invasion, as well as induced G0/G1 arrest and apoptosis in SW-620 cells. Moreover, the ectopic expression of miR-466 decreased the expression of cyclin D1 and MMP-2, but increased BAX expression in SW-620 cells. In conclusion, our findings demonstrated that miR-466 functions as a suppressor miRNA in CRC and may be used as a prognostic factor in these patients.
Patients with pulmonary hypertension are at increased risk for postoperative pulmonary complications (PPCs). Herein, we review PPCs in pulmonary hypertension patients undergoing non-cardiac procedures under general anesthesia. The medical records of pulmonary hypertension patients who underwent surgery with general anesthesia between 2010 and 2017 were reviewed for PPCs. In addition we reviewed nursing-documented respiratory depressive episodes in the post-anesthesia care unit to assess the associations between these episodes and later PPCs. There were 20 PPCs among 128 patients who underwent 197 procedures (10.2 per 100 surgeries) [95% CI 6.7-15.2]. Of these, 5 occurred during anesthesia recovery and 15 following anesthesia recovery. Three-quarters of the PPCs occurred within 24 postoperative hours. All the PPCs were severe. The frequency of PPCs was significantly higher in those who experienced respiratory depression during anesthesia recovery vs. in those who did not (5/17, 29% vs. 10/175, 6%; odds ratio 5.15, 95% CI 1.58-16.81, p = 0.007). Increased PPC rates were observed among patients who were current/previous smokers and who routinely use benzodiazepines, and among those undergoing emergent surgery. With treatment, all PPCs resolved. The rate of PPCs in the population of contemporary surgical pulmonary hypertension patients was 10.2%, and three-quarters occurred during first 24 postoperative hours. Patients who had respiratory depression during anesthesia recovery were 5-fold more likely to experience later PPCs.
Pancreatic cancer is the fourth leading cause of cancer death, with a 5-year survival rate of only 1-4%. Integrin-mediated cell adhesion is critical for the initiation, progression, and metastasis of cancer. In this study we investigated the role of integrin b4 (ITGB4) and its phosphorylation at tyrosine Y1510 (p-ITGB4-Y1510) in the tumorigenesis of pancreatic cancer. We analyzed the expression of ITGB4 and p-ITGB4-Y1510 in pancreatic cancer tissue and cell lines using immunohistochemistry, Western blot, or semi-quantitative reverse transcription PCR. ITGB4 and p-ITGB4-Y1510 were highly expressed in pancreatic cancer (n = 176) compared with normal pancreatic tissue (n = 171). High p-ITGB4-Y1510 expression correlated with local invasion and distant metastasis of pancreatic cancer, and high ITGB4 was significantly associated with poor survival of patients. Inhibition of ITGB4 by siRNA significantly reduced migration and invasion of PC-1.0 and ASPC-1 cells. Overexpression of the mutant ITGB4-Y1510A (a mutation of tyrosine to alanine at 1510 position) in PC-1.0 and ASPC-1 cells not only blocked the ITGB4 phosphorylation at Y1510 but also suppressed the expression of ITGB4 (p < 0.05 vs. wild-type ITGB4). The transfection of PC-1.0 and ASPC-1 cells with ITGB4-Y1510A significantly decreased the level of p-mitogen-activated protein kinase kinase (MEK)1 (T292) and p-extracellular signal-regulated kinase (ERK)1/2 but did not affect the level of p-MEK1 (T386) and p-MEK2 (T394). Overall, our study showed that ITGB4 and its phosphorylated form promote cell migration and invasion in pancreatic cancer and that p-ITGB4-Y1510 regulates the downstream MEK1-ERK1/2 signaling cascades. Targeting ITGB4 or its phosphorylation at Y1510 may be a novel therapeutic option for pancreatic cancer.
Acute pancreatitis (AP) is a disease with significant morbidity and mortality. The aim of this study was to evaluate the prognostic role of inflammatory markers, particularly interleukins (ILs), in the course of AP and to determine the frequency of etiologic factors of AP. We included patients with AP who were treated at our institution from May 1, 2012 to January 31, 2015. Different laboratory parameters, including ILs, and the severity scoring systems Ranson's criteria and Bedside Index of Severity in Acute Pancreatitis (BISAP) were analyzed. AP was classified into mild and severe, and independent parameters were compared between these groups. The predictive performance of each parameter was evaluated using receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC). A binomial logistic regression was performed to evaluate Ranson's criteria and IL6, IL8, and IL10 (at admission and after 48 hours) in the course of AP. Overall, 96 patients were treated, 59 (61.5%) males and 37 (38.5%) females, average age 62.5 ± 16.8 years (range 22-91 years). The best predictor for the severity of AP was IL6, measured 48 hours after admission (AUC = 0.84). Other useful predictors of the severity of AP were lactate dehydrogenase (p < 0.001), serum glucose (p < 0.006), and difference in the platelet count (p < 0.001) between admission and after 48 hours (p < 0.001), hemoglobin (p < 0.027) and erythrocytes (p < 0.029). The major causes of AP were gallstones and alcohol consumption. According to our results, IL6 and Ranson score are important predictors of the severity of AP.
Major depressive disorder (MDD) is one of the most common psychiatric disorders characterized by major depressive episodes. Although great efforts have been made to develop antidepressant drugs that target the monoaminergic system, these drugs are effective in only approximately 50% of MDD patients. In this study, we established a model of depression in PC12 cells using corticosterone to investigate the effect of ketamine and nuclear factor-κB (NF-κB) on the cell viability, apoptosis, levels of pro-inflammatory cytokines, apoptosis-related molecules, and enzymes of the Krebs cycle. PC12 cells were divided into control (no treatment, NC), ketamine treatment (KT), ketamine treatment with the inhibition of NF-κB (KI), and ketamine treatment with the overexpression of NF-κB (KO) group. Blood serum samples were collected from patients with MDD (n = 10) and healthy controls (n = 10) between 2015 and 2017. Ketamine significantly increased the viability and decreased the apoptosis of PC12 cells in KT and KI vs. NC group, but not in KO group. The levels of anti-apoptotic molecules and Krebs cycle enzymes were significantly increased in KI vs. KT group, while the levels of pro-apoptotic molecules and pro-inflammatory cytokines were decreased in KI vs. KT group. In addition, the levels of pro-inflammatory cytokines in the serum of MDD patients were significantly increased. The antidepressant effect of ketamine was enhanced in KI and reduced in KO group. Our results indicate that ketamine exerts its antidepressant effect via the inhibition of apoptosis and inflammation and the activation of the Krebs cycle in PC12 cells. NF-κB might be a potential therapeutic target in MDD.
In patients with type 1 diabetes mellitus (T1DM) imaging studies have demonstrated an increased prevalence of left ventricular diastolic dysfunction and increased left ventricular mass (LVM) unrelated to arterial hypertension and ischemic heart disease. The aim of our study was to identify potential predictors of early subclinical changes in cardiac chamber size and function in such patients. Sixty-one middle-aged asymptomatic normotensive patients with T1DM were included in the study. Conventional and tissue Doppler echocardiography was performed and fasting serum levels of glucose, glycated hemoglobin (HbA1c), lipids, and creatinine were measured. We found moderate bivariate correlations of body mass index (BMI) with left atrial volume (r = 0.47, p < 0.01), LVM (r = 0.42, p < 0.01), left ventricular relative wall thickness (r = 0.32, p = 0.01), and all observed parameters of diastolic function of both ventricles. The five-year average value of HbA1c weakly correlated with the Doppler index of left ventricular filling pressure E/e´sept (r = 0.27, p = 0.04). We found no significant association of diabetes duration, five-year trend of HbA1c, serum lipids, and glomerular filtration rate with cardiac structure and function. After adjusting for other parameters, BMI remained significantly associated with left atrial volume, LVM as well as with the transmitral Doppler ratio E/A. In our study, BMI was the only observed parameter significantly associated with subclinical structural and functional cardiac changes in the asymptomatic middle-aged patients with T1DM.
We evaluated characteristics and different prognostic factors for survival in age-stratified high-grade glioma in a US cohort. Eligible patients were identified in the Surveillance, Epidemiology, and End Results (SEER) registries and stratified into 3 age groups: 20-39 years old (1,043 patients), 40-59 years old (4,503 patients), and >60 years old (5,045 patients). Overall and cancer-related survival data were obtained. Cox models were built to analyze the outcomes and risk factors. It showed that race was a prognostic factor for survival in patients 40 to 59 years old and in patients ≥60 years old. Partial resection was associated with lower overall survival and cause-specific survival in all age groups (overall survival: 20-39 yr: HR=6.41; 40-59 yr: HR=4.84; >60 yr: HR=5.06; cause-specific survival: 20-39 yr: HR=5.87; 40-59 yr: HR=4.01; >60 yr: HR=3.36). The study highlights that, while some prognostic factors are universal, others are age-dependent. The effectiveness of treatment approaches differs for patients in different age groups. Results of this study may help to develop personalized treatment protocols for glioma patients of different ages.
Several recent studies suggest that cancer stem cells (CSCs) are involved in intrinsic resistance to cancer treatment. Maintenance of quiescence is crucial for establishing resistance of CSCs to cancer therapeutics. F-box/WD repeat-containing protein 7 (FBXW7) is a ubiquitin ligase that regulates quiescence by targeting the c-MYC protein for ubiquitination. We previously reported that gefitinib-resistant persisters (GRPs) in EGFR-mutant non-small cell lung cancer (NSCLC) cells highly expressed octamer-binding transcription factor 4 (Oct-4) as well as the lung CSC marker CD133, and they exhibited distinctive features of the CSC phenotype. However, the role of FBXW7 in lung CSCs and their resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors in NSCLC is not fully understood. In this study, we developed GRPs from the two NSCLC cell lines PC9 and HCC827, which express an EGFR exon 19 deletion mutation, by treatment with a high concentration of gefitinib. The GRPs from both PC9 and HCC827 cells expressed high levels of CD133 and FBXW7, but low levels of c-MYC. Cell cycle analysis demonstrated that the majority of GRPs existed in the G0/G1 phase. Knockdown of the FBXW7 gene significantly reduced the cell number of CD133-positive GRPs and reversed the cell population in the G0/G1-phase. We also found that FBXW7 expression in CD133-positive cells was increased and c-MYC expression was decreased in gefitinib-resistant tumors of PC9 cells in mice and in 9 out of 14 tumor specimens from EGFR-mutant NSCLC patients with acquired resistance to gefitinib. These findings suggest that FBXW7 plays a pivotal role in the maintenance of quiescence in gefitinib-resistant lung CSCs in EGFR mutation-positive NSCLC.
Cervical esophageal cancer (CEC) is uncommon, accounting for less than 5% of all esophageal cancers. The management of CEC is controversial. This study investigated treatment outcomes and prognostic factors of survival in CEC patients undergoing definitive radiotherapy or concurrent chemoradiotherapy (CCRT). Ninety-one CEC patients were treated by intensity-modulated radiation therapy (IMRT) and three-dimensional conformal radiation therapy (3DCRT) between July 2007 and September 2017. The mean prescription dose was 64 Gy (range 54-70 Gy) delivered as 1.8-2.2 Gy per fraction per day, 5 days a week. Out of 91 patients, 34 received concurrent cisplatin-based chemotherapy (CT) including 18 patients who also received neoadjuvant CT. Overall survival (OS), locoregional failure-free survival (LRFFS), and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Prognostic factors of survival were determined in univariate (log-rank test) and multivariate (Cox proportional hazard model) analysis. Treatment-related toxicity was also assessed. Median follow-up time for all patients was 19 months. Two-year OS, LRFFS and PFS of all patients were 58.2%, 52.5% and 48.1%, respectively. Clinical stage was an independent prognostic factor for OS (HR = 2.35, 95% CI: 1.03-5.37, p = 0.042), LRFFS (HR = 3.84, 95% CI: 1.38-10.69, p = 0.011), and PFS (HR = 2.68, 95% CI: 1.11-6.45, p = 0.028). Hoarseness was an independent prognostic factor for OS (HR = 2.10, 95% CI: 1.05-4.19, p = 0.036). CCRT was independently associated with better LRFFS (HR = 0.33, 95% CI: 0.14-0.79, p = 0.012). 3DCRT and IMRT with concurrent CT is well-tolerated and may improve local tumor control in CEC patients. Advanced clinical stage and hoarseness are adverse prognostic factors for OS, LRFFS, and PFS in CEC.
Previous studies demonstrated dysregulation of different microRNAs in thyroid cancer. Tetraspanins (TSPANs) are cell surface proteins with critical roles in many cellular processes, and implications in tumor development. Here we investigated the role of miR-369-3p in papillary thyroid cancer (PTC) and its association with TSPAN13. miR-369-3p and the TSPAN13 gene expression profiles of 513 thyroid cancer and 59 normal thyroid tissues were downloaded from the Cancer Genome Atlas database. Thyroid cancer tissues were classified according to the histological type, grouped based on low and high median miR-369-3p and TSPAN13 expression, and analyzed in relation to overall survival (OS) of patients. Human PTC cell lines (TPC-1 and GLAG-66) and human embryonic kidney 293T (HEK293T) cells were used for in vitro analysis. Transfection experiments were performed with synthetic miRNA mimics for miR-369-3p and small interfering RNAs for TSPAN13. Relative expression of miR-369-3p and TSPAN13 mRNA was determined by RT-qPCR. Protein levels of TSPAN13 were determined by western blotting. Cell proliferation (CCK-8 assay), colony formation, and apoptosis (flow cytometry) were analyzed in transfected cells. Binding sites of miR-369-3p in TSPAN13 mRNA were determined by bioinformatics analysis and dual luciferase reporter assay. miR-369-3p was downregulated and TSPAN13 upregulated in PTC, follicular thyroid cancer, and tall cell variant tissues. Both low expression of miR-369-3p and high expression of TSPAN13 were associated with shorter OS in thyroid cancer patients. Overexpression of miR-369-3p significantly suppressed proliferation and promoted apoptosis in PTC cells. TSPAN13 was a direct target of miR-369-3p, and silencing of TSPAN13 phenocopied the effect of miR-369-3p mimics in PTC cells. Overall, the downregulation of miR-369-3p and consequent upregulation of its target TSPAN13 appear to be involved in pathophysiology of PTC.
Distant organ tumor dissemination is a major cause of breast cancer-related deaths. In 2010, we analyzed the prognostic importance of the circulating tumor markers (CTMs) cytokeratin 19 (CK19), CK20, epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) in relation to the clinical and pathological characteristics of patients with breast cancer (BC). To assess the clinical utility of CK19, CK20 and EGFR in predicting distant metastasis in BC, here we report 7-year follow-up results of 77 patients. The patients with at least one positive CTM were classified as CTM(+) and those negative for all CTMs were assigned to CTM(-) group. In patients who received no treatment following CTM analysis, 25.0% had metastasis in CTM(+) and 10.0% in CTM(-) group. In patients who received one of the following therapies: chemotherapy, radiotherapy or hormone therapy, or the combinations of these therapies, the rate of metastasis was 33.3% in CTM(+) and 20.0% in CTM(-) group. Disease-free time was shorter in CTM(+) patients compared to CTM(-) group (28.83 +/- 10.76 and 41.38 +/- 9.5 months, respectively). According to multivariate Cox proportional hazard regression analysis, the presence of regional lymph node metastasis, Ki-67 expression, higher tumor grade and CTM expression status were predictors of poor prognosis associated with distant metastasis (p 0.05). Our findings demonstrate that CTM positivity may indicate a high metastasis risk; however, CTM negativity does not guarantee low metastasis risk. These results may encourage further preclinical investigation of CTMs, to evaluate the possible implications of these findings to the clinical setting.
Long non-coding RNAs (lncRNAs) are emerging as important modulators of cancer progression, among which prostate cancer-associated transcript 1 (PCAT1) has been shown to be an oncogene in several tumors. However, the clinical significance and biological function of PCAT1 in endometrial carcinoma (EC) remain unclear. In this study, we used 89 EC tissues and HEC-1B, Ishikawa, RL95-2 and AN3CA EC cell lines. We found elevated expression levels of PCAT1 in EC tissues and cell lines using reverse transcription qPCR (RT-qPCR). The prognostic value of PCAT1 was determined using Kaplan-Meier survival and Cox regression analysis. The results showed that higher PCAT1 expression was positively correlated with FIGO stage, myometrial invasion, lymph node metastasis, and a shorter overall survival. A series of functional assays showed that the knockdown of PCAT1 by small interfering RNA (siRNA) targeting PCAT1 (siPCAT1) suppressed cell proliferation, migration and invasion, but promoted apoptosis. Western blot analysis further showed that B-cell lymphoma 2 (Bcl-2), vimentin and N-cadherin were downregulated, but E-cadherin and Bcl-2-associated death promoter (Bad) were upregulated in PCAT1-silenced EC cells. Taken together, our results underscore the oncogenic role of PCAT1 in EC and show that PCAT1 may be a potential therapeutic target in EC treatment.
In some non-small cell lung cancer (NSCLC) patients, lipid-poor adrenal adenomas cannot be adequately differentiated from metastases using imaging methods. Invasive diagnostic procedures also have a low negative predictive value (NPV) in such cases. The current study aims to establish a specific and clinically practical metabolic parameter for lipid-poor adrenal lesions (ALs) in NSCLC patients. This diagnostic approach may prevent unnecessary abdominal enhanced computed tomography (CT), magnetic resonance imaging, or invasive diagnostic procedures. Sixty-four NSCLC patients with 69 lipid-poor ALs and 28 control patients with 30 benign lipid-poor ALs, who underwent FDG-PET/CT, were retrospectively reviewed. Two morphological and four metabolic parameters were analyzed in FDG-PET/CT images of NSCLC and control patients. Baseline and post-chemotherapy images of 64 NSCLC patients were re-evaluated according to the PERCIST 1.0. In cases where ALs could not be differentiated, follow-up FDG-PET/CT images were re-examined. The receiver operating characteristic (ROC) curve method was used for the evaluation of diagnostic parameters. Out of 69 ALs, 39 were determined as metastatic lesions (adrenal metastasis), while 30 lesions were considered non-metastatic (adrenal adenomas). The mean attenuation value, SUVmax AL/SUVmax primary tumor, SUVmax, SUVmax AL/liver, and SUVmax AL/SUVmean liver were significantly different between metastatic and benign ALs from NSCLC patients. The SUVmax AL/SUVmean liver >= 1.81 had the best positive (PPV, 94.3%) and negative (NPV, 82.4%) predictive values, and the highest specificity (93.3%), sensitivity (84.6%) and accuracy (86.9%). Lipid-poor ALs with SUVmax AL/SUVmean liver >= 1.81 can be accepted as malignant in NSCLC. However, if SUVmax AL/SUVmean liver is <1.81, a pathologic examination is required. Utilizing this cut-off value to decide on adrenal core biopsy may prevent its unnecessary use. Moreover, this diagnostic approach can save time and reduce the healthcare costs.
This study investigated the antidiabetic activity of Cinnamomum cassia (C. cassia, Cc) silver nanoparticles (CcAgNPS) and effects of C. cassia on the kidneys of rats with induced type 2 diabetes. Twenty-four Sprague-Dawley rats weighing 250 +/- 20 g were induced with diabetes by intraperitoneal injection of streptozotocin (STZ, 60 mg/kg). Animals were randomly assigned to one of four groups (n = 6) and treated for eight weeks with normal saline (control, group A), 5 mg/kg of CcAgNPs (group B), 10 mg/kg of CcAgNPs (group C), or 200 mg/kg of Cc (group D). Body weight and fasting blood glucose (FBG) was measured weekly and fortnightly, respectively. At the end of experiments animals were euthanized, blood and kidney tissue samples were collected for biochemistry (oxidative stress markers and renal function parameters) and kidneys were harvested for histology (PAS and H&E staining). Body weight was significantly higher in group B and C vs. control (p < 0.05), while no significant differences were observed in the kidney-to-body weight ratio between groups. FBG, glutathione, malondialdehyde, alanine aminotransferase, aspartate aminotransferase, serum urea and creatinine were significantly lower in group B, C and/or D vs. control (all p < 0.05). In group A, severe distortion of the glomerular network was observed, marked by the loss of capsular integrity, thickened basement membrane, tubular cells with pyknotic nuclei, vacuolization, and interstitial space with infiltrations. These adverse effects were mitigated by 5 mg/kg and 10 mg/kg of CcAgNPs. Our study confirms structural and functional damage to kidneys caused by diabetes. CcAgNPs have a regenerative potential in diabetes-induced kidney damage and may be used as an antidiabetic agent.
In vitro studies showed that high-frequency pulsed electromagnetic fields (HF-PEMFs) increase the activity/expression of early and late osteogenic markers and enhance bone mineralization. The main aim of this study was to investigate the in vivo effects of HF-PEMFs on fracture healing using a rat model. A femur fracture was established by surgery in 20 male Wistar rats. Titanium nails were implanted to reduce and stabilize the fracture. After surgery, 20 rats were equally divided into untreated control and treated group (from the first postoperative day HF-PEMFs at 400 pulses/sec [pps] were applied for 10 minutes/day, for two weeks). Quantitative and qualitative assessment of bone formation was made at two and eight weeks following surgery and included morphological and histological analysis, serological analysis by ELISA, micro-computed tomography (micro-CT), and three-point bending test. At two weeks in HF-PEMF group, soft callus was at a more advanced fibrocartilaginous stage and the bone volume/total tissue volume (BV/TV) ratio in the callus area was significantly higher compared to control group (p = 0.047). Serum concentration of alkaline phosphatase (ALP) and osteocalcin (OC) was significantly higher in HF-PEMF group (ALP p = 0.026, OC p = 0.006) as well as the mechanical strength of femurs (p = 0.03). At eight weeks, femurs from HF-PEMF group had a completely formed woven bone with dense trabeculae, active bone marrow, and had a significantly higher BV/TV ratio compared to control (p = 0.01). HF-PEMFs applied from the first postoperative day, 10 minutes/day for two weeks, enhance bone consolidation in rats, especially in the early phase of fracture healing.
Hematopoietic stem cell transplantation is commonly used in patients with certain hematological or bone marrow tumors. Total body irradiation combined with chemotherapy is part of the preconditioning protocol that was the most commonly used before hematopoietic stem cell transplantation. However, total body irradiation preconditioning damages other normal cells in bone marrow. Therefore, exploring the mechanism of radiation resistance in bone marrow mesenchymal stem cells is of great significance for recovering the hematopoietic function after cell transplantation. This study aimed to demonstrate the miR-29b adsorption of circRNA_014511 and explore the effect of circRNA_014511 on radiosensitivity of bone marrow mesenchymal stem cells. In this study, circRNA_014511 overexpression vector was constructed and transfected into bone marrow mesenchymal stem cells, miR-29b-2-5p and P53 were found to be decreased, which could be reversed by miR29b-mimics. Dual luciferase reporter assay confirmed the binding of circRNA_014511 and mmu-miR-29b-2-5p. Flow cytometry analysis showed the apoptosis rate of bone marrow mesenchymal stem cells overexpressing circRNA_014511 was significantly decreased. In the circRNA_014511 transfection group, after cells were subjected to 6Gy irradiation, G2 phase arrest appeared, the expression of P21 and GADD45A was significantly decreased, and cyclin B1 was significantly increased. Colony formation assay showed the survival fraction of circRNA_014511 overexpression cells after irradiation was significantly higher than control group, and the radiosensitivity was decreased. In conclusion, our findings demonstrated that circRNA_014511 could inhibit the expression of P53 by binding miR-29b-2-5p, and decrease the radiosensitivity of bone marrow mesenchymal stem cells by affecting cell cycle and cell apoptosis.
As important regulators of gene expression long noncoding RNAs (lncRNAs) are implicated in various physiological and pathological processes, including cancer. An oncogenic role of MNX1 antisense RNA 1 (MNX1-AS1) lncRNA has been suggested in cervical cancer and glioblastoma. In this study, we investigated the clinicopathological significance and biological function of MNX1-AS1 in gastric cancer (GC). The expression of MNX1-AS1 was analyzed by qRT-PCR in 96 GC and adjacent non-tumor tissues in relation to clinicopathological features and overall survival (OS) of patients, and in five human GC cell lines compared to a normal gastric epithelial cell line. Loss-of-function experiments using small interfering RNA (siRNA) targeting MNX1-AS1 (si-MNX1-AS1) were carried out in AGS and MGC-803 GC cell lines. Cell proliferation (CCK-8 assay), migration (Transwell) and invasion (Transwell Matrigel), and protein expression of proliferating cell nuclear antigen (PCNA), E-cadherin, N-cadherin, vimentin and matrix metallopeptidase 9 (MMP-9) were analyzed in transfected GC cells. Expression of MNX1-AS1 was significantly higher in GC vs. adjacent non-tumor tissues. Higher MNX1-AS1 expression was significantly associated with tumor size, TNM stage and lymph node metastasis. Kaplan-Meier analysis showed that GC patients with higher MNX1-AS1 expression had worse OS compared to patients with lower MNX1-AS1 expression. Multivariate analysis showed that MNX1-AS1 is an independent poor prognostic factor in GC. Knockdown of MNX1-AS1 significantly inhibited proliferation, migration and invasion of AGS and MGC-803 cells, and resulted in increased E-cadherin and decreased PCNA, N-cadherin, vimentin and MMP-9 expression. Taken together, these results suggest that MNX1-AS1 has an oncogenic function in GC and potential as a molecular target in GC therapy.
It is essential for a neurosurgeon to know individual anatomy and the corresponding anatomical landmarks before starting a surgery. Continuous training, especially of young neurosurgeons, is crucial for understanding complex neuroanatomy. In this study, we used a neuronavigation system with 3D volumetric image rendering to determine the anatomical relationship between the sagittal suture and the superior sagittal sinus (SSS) in patients with intracranial lesions. Furthermore, we discussed the applicability of such system in preoperative planning, residency training, and research. The study included 30 adult patients (18 female/12 male) who underwent a cranial computed tomography (CT) scan combined with venous angiography, for preoperative planning. The position of the sagittal suture in relation to the SSS was assessed in 3D CT images using an image guidance system (IGS) with 3D volumetric image rendering. Measurements were performed along the course of the sagittal sinus at the bregma, lambda, and in the middle between these two points. The SSS deviated to the right side of the sagittal suture in 50% of cases at the bregma, and in 46.7% at the midpoint and lambda. The SSS was displaced to the left of the sagittal suture in 10% of cases at the bregma and lambda and in 13% at the midpoint. IGSs with 3D volumetric image rendering enable simultaneous visualization of bony surfaces, soft tissue and vascular structures and interactive modulation of tissue transparency. They can be used in preoperative planning and intraoperative guidance to validate external landmarks and to determine anatomical relationships. In addition, 3D IGSs can be utilized for training of surgical residents and for research in anatomy.
The response to metformin, the most commonly used drug for the treatment of type 2 diabetes (T2D), is highly variable. The common variant rs7903146 C>T within the transcription factor 7 like 2 gene (TCF7L2) is the strongest genetic risk factor associated with T2D to date. In this study we explored the effects of TCF7L2 rs7903146 genotype on metformin response in T2D. The study included 86 newly diagnosed patients with T2D, incident users of metformin. Levels of fasting glucose, insulin, HbA1c, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and anthropometric parameters were measured prior to metformin therapy, and 6 and 12 months after the treatment. Genotyping of TCF7L2 rs7903146 was performed by the Sequenom MassARRAY® iPLEX® platform. At baseline, the diabetes risk allele (T) showed an association with lower triglyceride levels (p = 0.037). After 12 months of metformin treatment, the T allele was associated with 25.9% lower fasting insulin levels (95% CI 10.9-38.3%, p = 0.002) and 29.1% lower HOMA-IR index (95% CI 10.1-44.1%, p = 0.005), after adjustment for baseline values. Moreover, the T allele was associated with 6.7% lower fasting glucose levels (95% CI 1.1-12.0%, p = 0.021), adjusted for baseline glucose and baseline HOMA-%B levels, after 6 months of metformin treatment. This effect was more pronounced in TT carriers who had 16.8% lower fasting glucose levels (95% CI 7.0-25.6%, p = 0.002) compared to the patients with CC genotype. Our results suggest that TCF7L2 rs7903146 variant affects markers of insulin resistance and glycemic response to metformin in newly diagnosed patients with T2D within the first year of metformin treatment.
Measles are a highly contagious and communicable viral disease which may be prevented by a sustained vaccination program. Due to missed vaccination, two major epidemics of measles (1997–1999 and 2014–2015) have been recorded after the war in Bosnia and Herzegovina (BH) with over 10,000 patients registered. According to the World Health Organization, BH is categorized as a country with endemic transmission of measles. The last measles epidemic was between 2014 and 2015, with 5,083 documented patients in the Federation of BH. In the first four months of 2019, more than 700 measles cases were registered in the same region. Significant transmission rate has been observed in Sarajevo Canton (SC) with 570 documented measles cases. Out of 570 measles cases in SC, 92.5% were unvaccinated. The most affected were children up to 6 years of age (62.8%), with one documented case of death (7-month old infant). In addition to this report, we discussed key stakeholders and possible circumstances responsible for the epidemic. The measles epidemic is still ongoing.