Quercetin is a polyphenolic flavonoid, which is frequently found in fruits and vegetables. The antioxidant potential of quercetin has been studied from subcellular compartments, that is, mitochondria to tissue levels in the brain. The neurodegeneration process initiates alongside aging of the neurons. It appears in different parts of the brain as Aβ plaques, neurofibrillary tangles, Lewy bodies, Pick bodies, and others, which leads to Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and other diseases. So far, no specific treatment has been identified for these diseases. Despite common treatments that help to prevent the development of disease, the condition of patients with progressive neurodegenerative diseases usually do not completely improve. Currently, the use of flavonoids, especially quercetin for the treatment of neurodegenerative diseases, has been expanded in animal models. It has also been used to treat animal models of neurodegenerative diseases. In addition, improvements in behavioral levels, as well as in cellular and molecular levels, decreased activity of antioxidant and apoptotic proteins, and increased levels of antiapoptotic proteins have been observed. Low bioavailability of quercetin has also led researchers to construct various quercetin-involved nanoparticles. The treatment of animal models of neurodegeneration using quercetin-involved nanoparticles has shown that improvements are observed in shorter periods and with use of lower concentrations. Indeed, intranasal administration of quercetin-involved nanoparticles, constructing superparamagnetic nanoparticles, and combinational treatment using nanoparticles such as quercetin and other drugs are suggested for future studies.

Biomedical application of quercetin (QT) as an effective flavonoid has limitations due to its low bioavailability. Superparamagnetic iron oxide nanoparticle (SPION) is a novel drug delivery system that enhances the bioavailability of quercetin. The effect of short time usage of quercetin on learning and memory function and its signaling pathways in the healthy rat is not well understood. The aim of this study was to investigate the effect of free quercetin and in conjugation with SPION on learning and memory in healthy rats and to find quercetin target proteins involved in learning and memory using Morris water maze (MWM) and computational methods respectively. Results of MWM show an improvement in learning and memory of rats treated with either quercetin or QT-SPION. Better learning and memory functions using QT-SPION reveal increased bioavailability of quercetin. Comparative molecular docking studies show the better binding affinity of quercetin to RSK2, MSK1, CytC, Cdc42, Apaf1, FADD, CRK proteins. Quercetin in comparison to specific inhibitors of each protein also demonstrates a better QT binding affinity. This suggests that quercetin binds to proteins leading to prevent neural cell apoptosis and improves learning and memory. Therefore, SPIONs could increase the bioavailability of quercetin and by this way improve learning and memory.

Alzheimer’s disease (AD) is a neurodegenerative disease with cognitive impairment. Oxidative stress in neurons is considered as a reason for development of AD. Antioxidant agents such as quercetin slow down AD progression, but the usage of this flavonoid has limitations because of its low bioavailability. We hypothesized that quercetin-conjugated superparamagnetic iron oxide nanoparticles (QT-SPIONs) have a better neuroprotective effect on AD than free quercetin and regulates the antioxidant, apoptotic, and APP gene, and miRNA-101. In this study, male Wistar rats were subjected to AlCl3, AlCl3 + QT, AlCl3 + SPION, and AlCl3 + QT-SPION for 42 consecutive days. Behavioral tests and qPCR were used to evaluate the efficiency of treatments. Results of behavioral tests revealed that the intensity of cognitive impairment was decelerated at both the middle and end of the treatment period. The effect of QT-SPIONs on learning and memory deficits were closely similar to the control group. The increase in expression levels of APP gene and the decrease in mir101 led to the development of AD symptoms in rats treated with AlCl3 while these results were reversed in the AlCl3 + QT-SPIONs group. This group showed similar results with the control group. QT-SPION also decreased the expression levels of antioxidant enzymes along with increases in expression levels of anti-apoptotic genes. Accordingly, the antioxidant effect of QT-SPION inhibited progression of cognitive impairment via sustaining the balance of antioxidant enzymes in the hippocampus of AD model rats.

High-mobility group proteins are a superfamily of DNA-binding proteins that bind to the DNA minor groove and bend it, whereas most of the transcription factors such as centromere protein B (CENP-B), octamer (Oct)-1, growth factor independence 1 (Gfi-1), and WRKY bind to the major groove of DNA. Classification of proteins using their DNA-binding features is the aim of this study. Nuclear localization signals play more important roles in entering DNA-binding proteins to nucleus and doing their functions; therefore, they have been considered as a feature which is important for DNA-binding manner in proteins. Nuclear localization signals (NLSs) were predicted by two prediction web servers, and then, their sequence ordered features were extracted by Chou's pseudo amino acid composition (PseAAC) and ProtParam. Multilayer perceptron was used as an artificial neural network for analyzing the features by calculating the correlation coefficient and 30-fold cross-validation. Another used data-analyzing program was principal component analysis of the Minitab software. By calculating the eigenvalues and considering five principal components, the sequence length of NLSs was known as the best feature for classifying DNA-binding proteins. Minimum mean squared error (MSE) (0.1098) and the highest R (2) (0.963) mean that there is a significant difference between the NLS length of the DNA major groove and minor groove binder proteins. Results showed that it is possible to classify DNA major groove and minor groove binder proteins by their NLS sequences as a feature.

IntroductionBrain tumors (BTs) are perceived as one of the most common malignancies among children. The specific regulation of each gene can play a critical role in cancer progression. The present study aimed to determine the transcripts of the TSGA10 and GGNBP2 genes, considering the alternative 5′UTR region, and investigating the expression of these different transcripts in BTs.Material and methodsPublic data on brain tumor microarray datasets in GEO were analyzed with R software to evaluate the expression levels of TSGA10 and GGNBP2 genes (the Pheatmap package in R was also used to plot DEGs in a heat map). In addition, to validate our in-silico data analysis, RT-PCR was performed to determine the splicing variants of TSGA10 and GGNBP2 genes in testis and brain tumor samples. The expression levels of splice variants of these genes were analyzed in 30 brain tumor samples and two testicular tissue samples as a positive control.ResultsIn silico results show that the differential expression levels of TSGA10 and GGNBP2 were significant in the GEO datasets of BTs compared to normal samples (with adjusted p-value<0.05 and log fold change > 1). This study’s experimental results showed that the TSGA10 gene produces four different transcripts with two distinct promoter regions and splicing exon 4. The relative mRNA expression of transcripts without exon 4 was higher than transcripts with exon 4 in BT samples (p-value<001). In GGNBP2, exon 2 in the 5′UTR region and exon 6 in the coding sequence were spliced. The expression analysis results showed that the relative mRNA expression of transcript variants without exon 2 was higher than other transcript variants with exon 2 in BT samples (p-value<001).ConclusionThe decreased expression levels of transcripts with longer 5′UTR in BT samples than in testicular or low-grade brain tumor samples may decrease their translation efficiency. Therefore, decreased amounts of TSGA10 and GGNBP2 as potential tumor suppressor proteins, especially in high-grade brain tumors, may cause cancer development by angiogenesis and metastasis.