Identification of new SOX2OT transcript variants highly expressed in human cancer cell lines and down regulated in stem cell differentiation

Long non-coding RNAs are manifested as a new paradigm of molecular effectors in a wide range of human diseases. Human SOX2 overlapping transcript (SOX2OT) gene can generate six lncRNA transcript variants which are functionally assumed to be correlated with cellular differentiation and carcinogenesis. However, the circumstances determining expressional and functional differences between SOX2OT transcript variants remain to be explored. Here, we studied the expression of all SOX2OT transcript variants specifically in five human cancer cell lines by real-time RT-PCR. Changes of the new SOX2OT transcript variants expression were measured during the NT2 teratocarcinoma cell line neuronal-like differentiation and were compared to pluripotency regulators, SOX2 and OCT4A gene expressions. Surprisingly, we identified two new SOX2OT transcripts, named SOX2OT-7, SOX2OT-8 which lack exon 8. We discovered that beside active proximal and distal SOX2OT promoters, different cancer cell lines express high levels of some SOX2OT transcript variants differentially by alternative splicing. Significantly, both SOX2OT-7 and SOX2OT-8 are highly expressed in human cancer cell lines coinciding with SOX2, one of the pluripotency regulators. Our results revealed that SOX2OT-7 is almost the most abundant form of SOX2OT transcript variants in the examined cancer cell lines particularly in NT2 teratocarcinoma cell line where its expression falls upon neuronal-like differentiation similar to SOX2 and OCT4A. We suggest that at least some of SOX2OT transcripts are significantly associated with cancer and stem cell related pathways. © 2015, Springer Science+Business Media Dordrecht

Overexpression of the non-coding SOX2OT variants 4 and 7 in lung tumors suggests an oncogenic role in lung cancer

Despite the advances in cancer therapy, lung cancer still remains the most leading cause of cancer death worldwide. The long non-coding RNAs (lncRNAs) are recently introduced as novel regulators of human cancers. SOX2 overlapping transcript (SOX2OT) is a cancer-associated lncRNA gene that encodes different alternatively spliced transcripts. Here, we investigated the alterations in the preferential expression of different SOX2OTs in twenty non-small cell lung cancer (NSCLC) patients by real-time quantitative reverse transcription PCR (qRT-PCR) method. We observed preferential expression of SOX2OT4 and SOX2OT7 in lung tumor tissues. The quantitative gene expression analysis revealed that >30 % of NSCLC tumors express SOX2OT4 (mean = 7.6 times) and SOX2OT7 (mean = 5.9 times) more than normal tissues, with higher expression in squamous cell carcinoma. Further, we observed overexpression of pluripotency-associated transcription factor, SOX2 in 47 % of our samples concordant with SOX2OT (R = 0.62, P value <0.05). Overexpression of OCT4A gene was also observed in 36.8 % of tumor tissues. Then, we investigated the effects of SOX2OT suppression in lung adenocarcinoma cell line, by means of RNAi. Cell characteristics of colony formation, apoptosis, 2-D mobility, and cell cycle progression were measured in control and treated A549 cells. The SOX2OT knockdown significantly reduced the colony formation ability of cancer cells; however, no alterations in the rate of apoptosis were detected. On the other hand, SOX2OT-suppressed cells had elevated accumulation in G2/M phase of cell cycle and exhibited limited mobility. Altogether, our findings support a potential oncogenic role for SOX2OT in non-small cell lung cancer tumor genesis and SOX2OT seems a promising therapeutic candidate for NSCLC. © 2016, International Society of Oncology and BioMarkers (ISOBM)

Development of a fuzzy decision support system to determine the severity of obstructive pulmonary in chemical injured victims

Background: Chronic Obstructive Pulmonary Disease (COPD) is the most common known complication of exposure to mustard gas. Thus, all clinical guidelines have provided some recommendation for diagnosis, clinical management and treatment of this disease. Decision support systems are used to increase the acceptance of clinical guidelines. The purpose of this research is to develop a CDSS to determine the severity of COPD in chemical injured victims. Objectives: Development of a decision support system to determine the severity of COPD. Patients and Methods: First, the variables influencing to determining the severity of the disease was classified through studying the clinical guidelines. Then, the fuzzy model was implemented. To testing the system, the data from 50 patients were used. Results: the overall accuracy in determining the severity of the injury is equal to 92, these indicators reflect the proper functioning of the system to assist the physician regarding the diagnosis of chronic obstructive pulmonary disease and determining its severity. Conclusions: The CDSS has efficient results and satisfactory performance. Although, the medical expert systems cannot be expected to provide 100 percent correct responses, however, they can be useful in the areas of patient management, diagnosis and treatment planning. © 2015 Taha Samad-Soltani, Mostafa Ghanei, Mostafa Langarizadeh

Nondestructive examination of recovery stage during annealing of a cold-rolled low-carbon steel using eddy current testing technique

The recovery process in steel is usually investigated by conventional destructive tests that are expensive, time-consuming and also cumbersome. In this study, an alternative non-destructive test technique (based on eddy current testing) is used to characterise the recovery process during annealing of cold-rolled low-carbon steels. For assessing the reliability of eddy current results corresponding to different levels of recovery, X-ray line broadening analysis is also employed. It is shown that there is a strong relationship between eddy current outputs and the extent to which recovery occurs at different annealing temperatures. Accordingly, the non-destructive eddy current test technique represents the potential to be used as a reliable process for detection of the occurrence of recovery in the steel microstructure

The Association Between Obstructive Sleep Apnea and Depression in Older Adults

Background: Depression is the most frequent psychiatric disorder among the elderly. Obstructive sleep apnea (OSA) is a chronic and prevalent disease that has an ambiguous role in triggering depression. Several researches with contradictory findings have been performed about the association between OSA and depression. Objectives: This study aimed to investigate the association between OSA and depression among elderly. Patients and Methods: A total of 350 home residing elderly took part in this case-control study. The participants were selected using clustering method. All cases were divided into two groups of depressed and non-depressed using the geriatric depression scale (GDS). Then they were matched in age, gender, education and body mass index (BMI). Berlin questionnaire (BQ) was used to diagnose OSA. Data analysis was performed using Mann-Whitney U test, t-test, Chi-square and Fisher’s exact tests and odds ratio. Results: Totally, 60.6 % of depressed group and 18.9 % of non-depressed group were in high risk for OSA. A significant association was found between OSA and depression (P < 0.001, OR = 6.61, CI 95 % = 4.1 - 10.7). In addition, a significant association was found between gender and OSA (P = 0.008). Conclusions: OSA was associated with depression among the elderly patients. Given the high prevalence of OSA in older adults, implementation of screening methods is necessary to identify people at high risk of OSA

Comparison of the effectiveness and safety of formoterol versus salmeterol in the treatment of patients with asthma: A systematic review and meta-analysis

Background: Formoterol and salmeterol are two long-acting β2-agonists given by inhalation, with bronchodilating eff ects lasting for at least 12 h after a single administration. Formoterol has a faster onset of action compared with salmeterol. Th e aim of this study was to perform a systematic review and meta-analysis on the data published from previous review in order to calculate pooled estimates of eff ectiveness and safety assessment of formoterol and salmeterol in treatment of patients with asthma. Materials and Methods: In this study, we conducted an electronic search for medical citation databases including Cochrane, PubMed, Scopus, PsycInfo, and IranMedex. Besides manual search of the databases that record randomized clinical trials, conference proceedings, and journals related to asthma were included. Studies were evaluated by two independent people based on inclusion and exclusion criteria, and the common outcomes of studies were entered into the RevMan 5.0.1 software, after evaluation of studies and extraction of data from them; and in cases where there were homogeneous studies, meta-analysis was performed, and for heterogeneous studies, the results were reported qualitatively. Results: Of the 1539 studies initially found, 13 were included in the study. According to the meta-analysis conducted, no signifi cant diff erence was found between the inhalation of formoterol 12 μg and salmeterol 50 μg in the two outcomes of mean forced expiratory volume 1 s (FEV1), 12 h after inhalation of medication and Borg score (A frequently used scale for quantifying breathlessness) after inhalation of medication. In addition, salmeterol was more eff ective than formoterol in the two outcomes of percent decrease in FEV1 after inhalation of methacholine and the number of days without an attack. Since the two outcomes of FEV1 30-60 min after inhalation of medication and morning peak expiratory fl ow after inhalation of medication were heterogeneous, they had no meta-analysis capabilities, and its results were reported qualitatively. Conclusion: Th e data from included studies shows that, more effi cacy has been achieved with Salmeterol, especially in some outcomes such as the percent decrease in FEV1 after inhalation of Methacholine, and the number of days without an attack; and therefore, the administration of Salmeterol seems to be benefi cial for patients, compared with Formoterol. © 2015 Journal of Research in Medical Sciences

Characterization of lung fibroblasts more than two decades after mustard gas exposure

Purpose: In patients with short-term exposure to the sulfur mustard gas, the delayed cellular effects on lungs have not been well understood yet. The lung pathology shows a dominant feature consistent with obliterative bronchiolitis, in which fibroblasts play a central role. This study aims to characterize alterations to lung fibroblasts, at the cellular level, in patients with delayed respiratory complications after short-term exposure to the sulfur mustard gas. Methods: Fibroblasts were isolated from the transbronchial biopsies of patients with documented history of exposure to single high-dose sulfur mustard during 1985-7 and compared with the fibroblasts of control subjects. Results: Compared with controls, patients' fibroblasts were thinner and shorter, and showed a higher population doubling level, migration capacity and number of filopodia. Sulfur mustard decreased the in vitro viability of fibroblasts and increased their sensitivity to induction of apoptosis, but did not change the rate of spontaneous apoptosis. In addition, higher expression of alpha smooth muscle actin showed that the lung's microenvironment in these patients is permissive for myofibroblastic differentiation. Conclusions: These findings suggest that in patients under the study, the delayed pulmonary complications of sulfur mustard should be considered as a unique pathology, which might need a specific management by manipulation of cellular components. © 2015 Pirzad Jahromi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Increased Expression of Transforming Growth Factor-beta and Receptors in Primary Human Airway Fibroblasts from Chemical Inhalation Patients

The widespread use of sulfur mustard (SM) as a chemical warfare agent in the past century has proved its long-lasting toxic effects. Despite a lot of research over the past decades on Iranian veterans, there are still major gaps in the SM literature. Transforming growth factor (TGF-beta), a cytokine that affects many different cell processes, has an important role in the lungs of patients with some of chronic airway diseases, especially with respect to airway remodeling in mustard lung. Primary airway fibroblasts from epibronchial biopsies were cultured, and gene expression of TGF-beta 1, TGF-beta 2, TbR-I and TbR-II in fibroblasts of SM injured patients and controls were investigated. Expression of TGF-beta s and receptors was measured by RT-PCR. Protein level of TGF-beta 1 was surveyed by western blot. Our findings revealed that expression levels of TGF-beta 1, TGF-beta 2, TbR-I and TbR-II were upregulated in the airway fibroblasts of SM exposed patients in comparison with control samples. TGF-beta 1 expression was shown to be markedly increased in primary lung fibroblasts of chemically injured patients. Our novel data, suggested that over-expression of TGF-beta molecule and receptors in primary airway fibroblasts of mustard gas injured patients may be involved in progression of airway remodeling of these patients

Translation and validation of the Farsi version of the pain management self-efficacy questionnaire

Introduction: Pain management is a complex process that is managed through a multi-disciplinary team in which nurses have a significant role. The present study aimed at translating and examining the psychometric properties of the Pain Management Self-Efficacy Questionnaire (PMSEQ) among Iranian nurses. Methods: This was a cross-sectional, methodological study conducted in 2019 among nurses working in two teaching hospitals in Sanandaj (Tohid and Kosar). The participants were selected using a convenience sampling method. Responsiveness; interpretability; and face, content, and construct validities were examined using exploratory and confirmatory factor analyses. In addition, internal consistency and stability were examined using the Cronbach’s alpha, test-retest, respectively. Results: Overall, 410 nurses (210 for the EFA and 200 for the CFA) were included in the sample. In the exploratory factor analysis, two factors of Comprehensive pain assessment and Pain management with eigenvalues of 6.36 and 1.91, respectively, were extracted. The two factors together explained 56.64% of the variance of nurses’ pain management self-efficacy. The confirmatory factor analysis indicated that the model had a moderate fit to the data ((RMSEA: 0.12; NFI: 0.84; NNFI: 0.86; CFI: 0.88; IFI: 0.88; RFI: 0.81; GFI: 0.76; AGFI: 0.69; PGFI: 0.59; RMR: 0.09; Standardized RMR: 0.09). Total questionnaire and the two factors (i.e. Comprehensive pain assessment and Pain management) had internal consistency coefficients of 0.891, 0.876, and 0.803, respectively. Conclusion: The Farsi version of PMSEQ had good internal consistency and reliability, as well as content and construct validity, and can be used in future studies