Silencing of the MEG3 gene promoted anti-cancer activity and drug sensitivity in glioma

Aberrant expression of MEG3 has been shown in various cancers. The purpose of this study is to evaluate the effect of MEG3 on glioma cells and the use of potential chemotherapeutics in glioma by modulating MEG3 expression. Cell viability, migration and chemosensitivity were assayed. Cell death was evaluated in MEG3 overexpressing and MEG3 suppressed cells. MEG3 expression was compared in patient-derived glioma cells concerning IDH1 mutation and WHO grades. Silencing of MEG3 inhibited cell proliferation and reduced cell migration while overexpression of MEG3 promoted proliferation in glioma cells. MEG3 inhibition improved the chemosensitivity of glioma cells to 5-fluorouracil (5FU) but not to navitoclax. On the other hand, there is no significant effect of MEG3 expression on temozolamide (TMZ) treatment which is a standard chemotherapeutic agent in glioma. Suppression of the MEG3 gene in patient-derived oligodendroglioma cells also showed the same effect whereas glioblastoma cell proliferation and chemosensitivity were not affected by MEG3 inhibition. Further, as a possible cell death mechanism of action apoptosis was investigated. Although MEG3 is a widely known tumour suppressor gene and its loss is associated with several cancer types, here we reported that MEG3 inhibition can be used for improving the efficiency of known chemotherapeutic drug sensitivity. We propose that the level of MEG3 should be evaluated in the treatment of different glioma subtypes that are resistant to effective drugs to increase the potential effective drug applications.     

Baseline serum levels of cardiac biomarkers in patients with stable coronary artery disease

Stable coronary artery disease (CAD) can cause repetitive reversible myocardial ischaemia, and it seems to be possible that reversibly injured myocardium releases small amounts of soluble cytoplasmic proteins. Hence, the aim was to evaluate the effect of stable CAD on baseline serum levels of cardiac biomarkers. We studied 68 consecutive outpatients referred for gated myocardial perfusion imaging. Before a treadmill exercise test, blood samples for measurement of creatine kinase (CK), CK-myocardial band (CK-MB) mass, myoglobin, aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were collected. Normal perfusion patterns were detected in 29 (43%) patients (group 1) and perfusion defects were detected in 39 (57%) patients (group 2). Baseline serum levels of biomarkers except CK were significantly higher in group 2 (p=0.001). Stable CAD increases baseline levels of CK-MB mass, myoglobin, AST and LDH in the serum and this increase is related to the extent and severity of the perfusion defect and to some extent the ejection fraction of the left ventricle.     

Clock gene PERIOD3 polymorphism is associated with susceptibility to Graves’ disease but not to Hashimoto’s thyroiditis

ABSTRACT

Circadian disruption has been linked with immune-related morbidities including autoimmune diseases. PERIOD3 (PER3) clock gene is a key player in the mammalian circadian system. This study evaluated the possible association of PER3 rs2797685 (G/A) polymorphism and susceptibility of autoimmune thyroid diseases (AITD) and assessed if this SNP contributes to disease characteristics and serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). The PER3 rs2797685 (G/A) polymorphism was assessed in 125 patients with AITD [Graves’ disease (GD), 69; Hashimoto’s thyroiditis (HT), 56] and 115 unrelated healthy controls. Subjects carrying at least one variant allele of PER3 rs2797685 (GA+AA) had increased risk for GD (OR 1.9, 95% CI 1–3.61, p= .05). There were no differences in the frequencies of genotypes and alleles of the PER3 rs2797685 polymorphism between HT patients and control subjects. No association was observed between genotypes of the studied SNP and any of the disease characteristics in GD and HT patients. The GA+AA genotype of PER3 rs2797685 was associated with lower levels of IL-6 in patients with Graves’ disease. There were no differences between genotypes of the studied SNP regarding TNF-α levels in GD, HT or control groups. In conclusion, this study provides the first evidence for a genetic association between GD and the PER3 gene, highlighting the possible relevance of polymorphisms in clock genes in the etiopathogenesis of AITD. However, functional studies to identify the underlying molecular mechanisms of this association are needed to translate these findings to clinical applications.     

On-line preconcentration/determination of zinc from water,biological and food samples using synthesized chelating resin and flame atomic absorption spectrometry

An on-line flow injection pre-concentration-flame atomic absorption spectrometry method was developed to determine trace zinc in water (tap, dam, and well water), biological (hair and nail), and liver samples. As a solid phase extractant, a synthesized new chelating resin, poly(2-thiozylmethacrylamide-co-divinylbenzene-co-2-acrylamido-2-methyl-1-propane sulfonic acid) was used. The resin was characterized by Fourier transform infrared spectroscopy, elemental analysis, and surface area by nitrogen sorption. A pre-concentration factor of 40-fold for a sample volume of 12.6 mL was obtained by using the time-based technique. The detection limit for the pre-concentration method was found to be 2.2 μg L^?1. The precision (as RSD,%) for 10 replicate determinations at the 0.04 μg mL^?1 Zn concentration was 1.2%. The calibration graph using the pre-concentration system for zinc was linear with a correlation coefficient of 0.998 in the concentration range from 0.005 to 0.05 μg mL^?1. The applicability and accuracy of the developed method were estimated by the analysis spiked water, biological, liver samples (83–105%), and also certified reference material TMDA-70 (fortified lake water) and SPS-WW1 Batch 111-Wastewater. The results were in agreement with the certified values.     

Crimean-Congo hemorrhagic fever: An overview

Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic viral infection that is a serious threat to humans. The disease is widely distributed in Africa, Asia, and Europe and has developed into a serious public health concern. Humans become infected through the bites of ticks, by contact with a patient with CCHF, or by contact with blood or tissues from viremic livestock. Microvascular instability and impaired hemostasis are the hallmarks of the infection. Infection in human begins with nonspecific febrile symptoms, but may progress to a serious hemorrhagic syndrome with high mortality rates. Enzyme-linked immunoassay (ELISA) and polymerase chain reaction (PCR) are the most used and specific tests for the diagnosis. The mainstay of treatment is supportive. Although definitive studies are not available, ribavirin is suggested to be effective especially at the earlier phase of the infection. Uses of universal protective measures are the best way to avoid the infection. In this review, all aspects of CCHF are overviewed in light of the current literature.     

Nitric oxide: a novel inducer for enhancement of microbial lipase production

The purpose of this study was to elucidate whether exogenous nitric oxide (NO) has a potential beneficial effect on lipase production capacity of some microorganisms. Sodium nitroprusside (SNP) was used as an exogenous NO donor in production medium. In comparison with the control (0 nM SNP), SNP concentrations from 10 to 100 nM induced lipase production in mesophilic bacterium Bacillus subtilis and cold-adapted yeast Yarrowia lipolytica. Especially, the maximum lipase activities for Y. lipolytica (81.2 U/L) and B. subtilis (74.5 U/L) were attained at 30 and 50 nM SNP concentrations, respectively. When compared to the control, the optimal SNP concentrations resulted in about 5.14 and 2.27-fold increases in lipase activities of B. subtilis and Y. lipolytica, respectively. Besides, it was found that the optimal SNP concentrations provided shorter incubation periods for lipase production. Conversely, no significant positive effect of exogenous NO on lipase production was determined for thermophilic bacterium Geobacillus stearothermophilus. This study showed for the first time that exogenous NO could be used as an inducer in the production of microbial lipases.     

Efficient Pre-mRNA Cleavage Prevents Replication-Stress-Associated Genome Instability

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