Circulating long noncoding RNAs H19 and GAS5 are associated with type 2 diabetes but not with diabetic retinopathy: A preliminary study

Recently, a wide range of biological and pathological roles of long noncoding RNAs (lncRNAs) have been discovered. However, the potential role of circulating lncRNAs H19 and GAS5 in type 2 diabetes mellitus (T2DM) and diabetic retinopathy (DR) is not clear. Here, we assessed the plasma levels of H19 and GAS5 lncRNAs in T2DM patients with/without DR and evaluated if H19 and GAS5 pre-treatment plasma levels are a predictor of early response to a single aflibercept dose in DR subgroup. Plasma lncRNA expression profiles of 119 T2DM patients (66 with DR and 53 without DR) and 110 healthy controls were determined by quantitative reverse transcription PCR. The association of lncRNA expression profiles with clinical features and aflibercept early response in DR patients was investigated. Relative H19 expression levels were significantly increased in T2DM group (including DR and non-DR subgroups) vs. controls, while GAS5 levels were decreased in T2DM group (p < 0.001). There was no significant difference in H19 and GAS5 expression levels between DR and non-DR subgroups. H19 and GAS5 expression profiles were not significantly correlated with clinical parameters or response to aflibercept therapy in DR subgroup. Our findings indicate that the circulating lncRNAs H19 and GAS5 may be associated with T2DM prevalence but may not have an important diagnostic/prognostic role in DR or early response to aflibercept intravitreal injection in DR patients. Large-scale transcriptomic studies are warranted to validate our results and investigate other lncRNA candidates in T2DM

MicroRNA-34a: A Key Regulator in the Hallmarks of Renal Cell Carcinoma

Renal cell carcinoma (RCC) incidence has increased over the past two decades. Recent studies reported microRNAs as promising biomarkers for early cancer detection, accurate prognosis, and molecular targets for future treatment. This study aimed to evaluate the expression levels of miR-34a and 11 of its bioinformatically selected target genes and proteins to test their potential dysregulation in RCC. Quantitative real-time PCR for miR-34a and its targets; MET oncogene; gene-regulating apoptosis (TP53INP2 and DFFA); cell proliferation (E2F3); and cell differentiation (SOX2 and TGFB3) as well as immunohistochemical assay for VEGFA, TP53, Bcl2, TGFB1, and Ki67 protein expression have been performed in 85 FFPE RCC tumor specimens. Clinicopathological parameter correlation and in silico network analysis have also implicated. We found RCC tissues displayed significantly higher miR-34a expression level than their corresponding noncancerous tissues, particularly in chromophobic subtype. MET and E2F3 were significantly upregulated, while TP53INP2 and SOX2 were downregulated. ROC analysis showed high diagnostic performance of miR-34a (AUC = 0.854), MET (AUC = 0.765), and E2F3 (AUC = 0.761). The advanced pathological grade was associated with strong TGFB1, VEGFA, and Ki67 protein expression and absent Tp53 staining. These findings indicate miR-34a along with its putative target genes could play a role in RCC tumorigenesis and progression

Longevity-Related Gene Transcriptomic Signature in Glioblastoma Multiforme

Glioblastoma multiforme (GBM) (grade IV astrocytoma) has been assumed to be the most fatal type of glioma with low survival and high recurrence rates, even after prompt surgical removal and aggressive courses of treatment. Transcriptional reprogramming to stem cell-like state could explain some of the deregulated molecular signatures in GBM disease. The present study aimed to quantify the expression profiling of longevity-related transcriptional factors SOX2, OCT3/4, and NANOG to evaluate their diagnostic and performance values in high-grade gliomas. Forty-four specimens were obtained from glioblastoma patients (10 females and 34 males). Quantitative real-time polymerase chain reaction was applied for relative gene expression quantification. In silico network analysis was executed. NANOG and OCT3/4 mRNA expression levels were significantly downregulated while that of SOX2 was upregulated in cancer compared to noncancer tissues. Receiver operating characteristic curve analysis showed high diagnostic performance of NANOG and OCT3/4 than SOX2. However, the aberrant expressions of the genes studied were not associated with the prognostic variables in the current population. In conclusion, the current study highlighted the aberrant expression of certain longevity-associated transcription factors in glioblastoma multiforme which may direct the attention towards new strategies in the treatment of such lethal disease

Data supporting the structural and functional characterization of Thrombin‐Activatable Fibrinolysis Inhibitor in breast cancer

AbstractThe data in this paper is related to the research article entitled “Thrombin-activatable fibrinolysis inhibitor Thr325Ile polymorphism and plasma level in breast cancer: A pilot study” (Fawzy et al., 2015) [1]. Many emerging studies have begun to unravel the pathophysiologic role of the fibrinolytic system in breast cancer (BC) progression (Zorio et al., 2008) [2]. Activation of the fibrinolytic plasminogen/plasmin system results in degradation of protein barriers, thereby mediating cell migration essential for tumor growth, angiogenesis, and dissemination (Castellino and Ploplis, 2005) [3]. In the current study, in silico data analysis of Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) gene and protein has been done. Data have been retrieved from several databases mentioned in details in the text. Determination and analysis of the structural and functional impact of TAFI and its expression could help elucidate the contribution of the TAFI pathway to acquired hemostatic dysfunction and will form the basis of potential therapeutic strategies to manipulate this pathway. An inhibition of TAFI (e.g. by FXI inhibitors) will offer the therapeutic possibilities to improve the decreased fibrinolysis and increase the efficiency of fibrinolytic therapy in thrombotic disorders including cancer

Serum S100B: A possible biomarker for severity of obstructive sleep apnea

Introduction: Obstructive sleep apnea (OSA) is characterized by upper airway collapsibility and intermittent hypoxia (IH) during sleep. It has neurological complications and it has been associated with morbidity and mortality. Increased serum levels of S100B protein indicates brain injury. Early detection of possible complications of OSA patients could improve management of the disease. Study objective: Measurement of serum S100B protein in OSA patients with correlation to the severity of the disease. Patients and methods: Fifty five OSA patients (24 females; 43.6% and 31 males; 56.4%) and 34 control individuals (17 females; 50% and 17 males; 50%) had a sleep apnea monitoring using the SAM equipment, Inter care technologies, model 100, USA, and S100B serum levels were measured after the sleep study at 6.30–7.30 am. Results: S100B serum levels were higher in patients than controls (P < 0.001) and the levels correlated with the apnea/hypopnea index (AHI) (P < 0.001), lowest oxygen saturation (LOS) (P < 0.001), and oxygen desaturation index (ODI) (P < 0.001). Conclusion: Serum S100B protein was significantly elevated in OSA patients and its serum levels correlated with the severity of the disease. Increased serum S100B could indicat brain injury and could be a potential serum biomarker for detection of early neurological complications in OSA patients that could improve the management and care of these patients

Mobile phones electromagnetic radiation and NAD+-dependent isocitrate dehydrogenase as a mitochondrial marker in asthenozoospermia

AbstractNAD+-dependent Isocitrate Dehydrogenase (NAD+-IDH) could be one of the cell phone radiation targets. Enzyme activity alteration may lead to decline in sperm motility during radio-frequency electromagnetic waves (RF-EMW) exposure. The current case control study aimed to investigate the possible relationship between mitochondrial NAD+-IDH activity in human seminal plasma and sperm motility among asthenozoospermic cellular phone users. A total number of ninety idiopathic infertile males referred from the Department of Dermatology and Andrology, were enrolled in this study. NAD+-IDH activity was measured in human seminal plasma by spectrophotometer. Computer-aided sperm analysis (CASA) following WHO criteria has been used for semen analyses. The results showed that IDH activity was increased in patients with prolonged cell phone daily use ≥4 h/day. Its level, correlated negatively with either the motility ratio percentages (r = −0.46, p < 0.001) or the progressive motility percentages (r = −0.50, p < 0.001) in the study groups. The current study suggests that NAD+-IDH in human seminal plasma could be one of seminal plasma biomarkers reflecting the mitochondrial function of spermatozoa. Alteration of its level could reflect the defective motility of sperms among some cases of cellular phone users

Long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1): A molecular predictor of poor survival in glioblastoma multiforme in Egyptian patients

AbstractBackgroundLong noncoding RNAs (lncRNAs) are a recently discovered class of transcribed RNA molecules with a length of more than 200 nucleotides. Recent studies have shown that lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) could play an important role in carcinogenesis and cancer progression in several types of malignancies.ObjectiveAs little is known about the role and clinical significance of lncRNA MALAT1 in glioblastoma multiform (GBM) patients in Egyptian population, this study aimed to investigate the expressions of lncRNA-MALAT1 in human GBM samples and to correlate these expressions with the available clinicopathological features including patient survival data.Subjects and methodsThe relative expression of MALAT1 was determined in 37 human glioblastoma formalin-fixed paraffin embedded (FFPE) tissue samples and 10 FFPE non-neoplastic brain tissues using quantitative reverse transcription polymerase chain reaction (qRT-PCR) technology.ResultsThe current results revealed that lncRNA MALAT1 expression was down-regulated in all tumor specimens compared to normal tissues. A receiver operating characteristic (ROC) curve analysis showed high diagnostic performance; area under curve (AUC)=0.925±0.038 (P<0.001), 95% CI=0.850–1.00, with 94.6% sensitivity, and 72.7% specificity. Lower MALAT1 expression was associated with poor prognosis; higher frequency of recurrence (P<0.044), lower overall survival (P<0.005), and shorter disease-free survival (P<0.004).ConclusionTaken together, we could postulate that MALAT1 might have a tumor-suppressive function in GBM in Egyptian population and this specific type of lncRNAs may be included in the lists of both potential prognostic biomarkers and the future therapeutic targets for glioblastomas