Effect Of Different Doses Of Noradrenaline Against Ischemia-induced Ventricular Arrhythmias In Rat Heart In Vivo

Background

The present study was designed to evaluate the preconditioning effect of different doses of noradrenaline on ischemia-induced ventricular arrhythmias in open chest anesthetized rats.

Methods

The anaesthetized rats were subjected to 25 min of regional ischemia by left descending coronary artery (LAD) occlusion. In sham group, surgical procedures were done but ischemia was not applied. In control rats, saline was injected prior to ischemia. In noradrenaline groups, rats pretreated with three different doses of noradrenaline (respectively, 0.5, 1 and 2 μg/kg, IV).

Results

In control rats, induction of ischemia shortened the QTc (corrected QT) interval (ms) and led to occurrence of ventricular arrhythmias. Administration of low-dose of noradrenaline prevented shortening of the QTc interval during ischemia but could not significantly attenuate severity and incidences of arrhythmias. Injection of mid-dose of noradrenaline stabilized the QTc during ischemia and reduced severity of arrhythmias. Pretreatment with high-dose of noradrenaline significantly prolonged the QTc interval and declined severity and incidence of arrhythmias.

Conclusions

Noradrenaline dose-dependently attenuated ischemia-induced ventricular arrhythmias.     

Genetic variants in 3′‐UTRs of MTHFR in the pregnancies complicated with preeclampsia and bioinformatics analysis

Preeclampsia (PE) as a pregnancy‐specific disorder is the major cause of mortality and morbidity of mothers and fetuses. This study attempts to investigate the possible association between the 2572C>A (rs4846049) and 4869C>G (rs1537514) polymorphisms in the 3′‐ untranslated region of MTHFR gene and the risk of PE. A total of 198 patients diagnosed with PE and 171 unrelated, age matched healthy pregnant women, were recruited for this case‐control study. The MTHFR 2572C>A and 4869C>G genotyping was performed by the polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) method. The CG genotype of MTHFR 4869C>G was associated with decreased risk of PE, and this genotype was found to be a protective factor for PE susceptibility. There was no significant difference in the genotypes of MTHFR 2572C>A polymorphism between PE patients and control group. The frequency of combined AC/CG genotypes of MTHFR 2572C>A and 4869C>G polymorphisms were less frequent in PE patients and were associated with a lower risk of PE. The C‐G and A‐G haplotypes of MTHFR 2572C>A and 4869C>G polymorphisms were significantly lower in PE patients. In conclusion, the CG genotype of MTHFR 4869C>G polymorphism was associated with a lower risk of PE. No association was found between MTHFR 2572C>A polymorphism and PE.     

Production and Characterization of Single Chain Nimotuzumab: An In Vitro Study

Recombinant expression and EGFR-binding activity assay of single chain nimotuzumab (nimotuzumab scFv) is reported in this study. The scFv was produced in VH-linker-VL format in Origami^? 2(DE3)pLysS bacterial cells and purified using Ni-TNA resin column. 3-D structure prediction using I-TASSER (Iterative Threading Assembly Refinement) server and analyzing the predicted models using YASARA (Yet Another Scientific Artificial Reality Application) viewer revealed that VH and VL domains assemble into a correctly-folded single chain antibody that is able to bind EGFR. The scFv was evaluated in ELISA and western blot tests and proven to be able to bind EGFR-overexpressing cancer cells (A-431 cells in an efficient manner but unable to recognize cancer cells expressing low levels of EGFR (MCF-7 breast cancer cells).     

ARA lncRNA,is upregulated in liver and breast tumor tissues

Molecular Biology Reports - Important regulatory roles of long non-coding RNAs (lncRNAs) have been recently found, and reported as useful biomarkers in cancer. To identify a potential expression of...     

Biophysical study on the interaction of cartap hydrochloride and hemoglobin: Heme degradation and functional changes of protein

Cartap hydrochloride is a mildly perilous insecticide known as “Padan” which is used largely in agricultural farms to control weevil and caterpillars. The over use of cartap causes harmful effects on human health. Since the blood may acts as a target and carrier for insecticides, the effect of these compounds on blood in mammalian toxicology is very important. Hemoglobin is a tetramer protein that play critical role in oxygen transport. The aim of this study was to analyze and compare the function and structural changes of hemoglobin in the presence of different concentrations of cartap by employing different spectroscopic techniques. The obtained results show that cartap has a high hemolytic effect which is increased with cartap concentration and reduces the thermal midpoint of hemoglobin. Fluorescence measurements reveal heme degradation at different concentrations of cartap. In consequence of theoretical and experimental results, cartap has an undesirable effect on hemoglobin structure and function.     

Prediction of Genes Involved in Lung Cancer with a Systems Biology Approach Based on Comprehensive Gene Information

Biochemical Genetics - Over the past few years, hundreds of genes have been reported in relation to lung cancer. Systems biology studies can help validate this association and find the most valid...     

Whole-Exome Sequencing Identified a Novel Variant (C.405_422+39del) in DSP Gene in an Iranian Pedigree with Familial Dilated Cardiomyopathy

Background:Dilated cardiomyopathy (DCM) is a progressive heart condition characterized by left ventricular chamber enlargement associated with systolic heart failure and prolonged action potential duration. Genetic variations in genes that encode cytoskeleton, sarcomere, and nuclear envelope proteins are responsible for 45% of cases. In our study, we focused on a pedigree with familial DCM to decipher the potential genetic cause(s) in affected members developing arrhythmia, end-stage heart failure, and sudden death. Methods:Whole-exome sequencing (WES) was exploited for a 27-year-old heart-transplanted female as the proband, and the derived data were filtered using the standard pipelines.Results:A 57-nucleotide deletion (c.405_422+39del) in the desmoplakin gene (DSP) ({"type":"entrez-nucleotide","attrs":{"text":"NM_004415.4","term_id":"1519314167"}}NM_004415.4) was identified as a novel pathogenic variant. Familial segregation analysis indicated that this variant is present in clinically affected members and absent in unaffected members. Conclusion:It seems that the detected variant induces intron retention, resulting in a premature stop codon in intron 3 of DSP leading to production of a truncated, nonfunctional protein. Additionally, it can trigger a nonsense-mediated mRNA decay pathway associated with inhibition of protein production. The present study results illustrated that a novel deletion in DSP can cause DCM in an Iranian family.Key Words: Desmoplakin, Dilated cardiomyopathy, Pathogenic variant, Whole exome sequencing     

Enhanced Plasmonic Light Absorption for Silicon Schottky-Barrier Photodetectors

Quantum efficiency of the silicon Schottky-barrier photodetector is limited by the weak interaction between the photons and electrons in the metal. By engineering the metal surfaces, metallic groove structures are proposed to achieve strong light absorption in the metal, where most of the energy is transferred into hot carriers near the Schottky barrier. The proposed broadband photodetector with a bi-grating metallic structure on the silicon substrate enables to absorb 76 % of the infrared light in the metal with a 200-nm bandwidth, while staying insensitive to the incident angle. These results pave a new promising way to attain high quantum efficiency silicon Schottky-barrier photodetectors.     

Enhanced anticancer potency of doxorubicin in combination with curcumin in gastric adenocarcinoma

Gastric cancer (GC) is one of the prevalent human malignancies and the third most common cause of cancer‐related death worldwide. The doxorubicin hydrochloride is one of the important chemotherapeutic anticancer agents, with a limited therapeutic efficacy for treatment of GC. Therefore, taking advantage of synergistic effects by strategies like combination therapy seems appropriate and promising in treatment of GC. The aim of this study was to investigate a novel method to enhance the therapeutic efficacy of doxorubicin (as a chemotherapeutic agent) by co‐administration of curcumin (as a bioactive herbal compound) in GC treatment. In the present study, the effects of curcumin, doxorubicin, and their combinations (Dox‐Cur) were evaluated on the viability, morphological features, tumor spheroid formation, migration, invasion, and apoptosis of gastric adenocarcinoma cell line (AGS). Moreover, expression levels of BAX, BCL‐2, and CASP9 genes were assessed among AGS cells treated with curcumin, doxorubicin, and Dox‐Cur. The obtained results showed that all of curcumin, doxorubicin, and Dox‐Cur treatments significantly decreased the viability, tumor spheroid formation, migration, and invasion in the GC model cells. Furthermore, apoptosis rates in AGS cells were increased in a concentration‐ and time‐dependent manner in all of the treatment groups. Moreover, the anticancer activity of the Dox‐Cur combination was significantly more than curcumin and doxorubicin treatments alone. According to the results, Dox‐Cur combination therapy exerts more profound apoptotic and anticancer effects on the AGS cell line than curcumin or doxorubicin monotherapy.