Analysis of histaminergic system genes expression level in the early symptom stage of Parkinson’s disease

Целью данной работы было изучение изменений экспрессии генов гистаминергической системы в развитии патологических процессов при болезни Паркинсона (БП) на ранней симптомной стадии. На МФТП-индуцированной модели ранней симптомной стадии БП (мыши-самцы линии C57BL/6 по 10 шт. в контрольной и опытной группах) проанализирована экспрессия 9 генов, имеющих отношение к гистаминергической системе, методом обратной транскрипции и ПЦР в реальном времени (TaqMan). В результате были выявлены изменения на уровне мРНК для ряда генов в тканях мозга мышей, которые могут указывать на вовлеченность гистаминергической системы в патогенез БП на ранней стадии. The goal of this work was to study changes of histaminergic system genes expression level in the early symptom stage of PD. We were use MPTP mouse model of early symptom stage of PD in this study. Male mice C57BL/6 were used (n=10 in the control and experimental groups). For analysis we were choose nine genes, which associated with histaminergic system. Measuring of expression levels was carried out using reverse transcription reaction and real-time PCR (TaqMan). Changes at the mRNA level for a number of genes in the brain tissues of mice with MPTP-induced PD were founded. Based on these data, it can be suggested that histaminergic system is involve in early stage PD pathogenesis.

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Impact of Curcuma longa extract on the expression level of brain transporters in in vivo model

Herba Polonica ◽

10.2478/hepo-2019-0005 ◽

2019 ◽

Vol 65 (1) ◽

pp. 32-39

Author(s):

Marta Bukowska ◽

Anna Bogacz ◽

Marlena Wolek ◽

Przemysław Ł. Mikołajczak ◽

Piotr Olbromski ◽

...

Keyword(s):

Blood Brain Barrier ◽

Curcuma Longa ◽

Mrna Level ◽

Expression Level ◽

Brain Barrier ◽

In Vivo Model ◽

Toxic Substances ◽

Blood Brain ◽

The Brain

Summary Introduction: Blood brain barrier and multidrug resistance phenomenon are subjects of many investigations. Mainly, because of their functions in protecting the central nervous system (CNS) by blocking the delivery of toxic substances to the brain. This special function has some disadvantages, like drug delivery to the brain in neurodegenerative diseases Objective: The aim of this study was to examine how natural and synthetic substances affect the expression levels of genes (Mdr1a, Mdr1b, Mrp1, Mrp2, Oatp1a4, Oatp1a5 and Oatp1c1) that encode transporters in the blood-brain barrier. Methods: cDNA was synthesized from total RNA isolated from rat hippocampus. The expression level of genes was determined using real-time PCR (RT-PCR) method. Results: Our findings showed that verapamil, as a synthetic substance, caused the greatest reduction of mRNA level of genes studied. The standardized extract of Curcuma longa reduced the expression level for Mrp1 and Mrp2, whereas the increase of mRNA level was observed for Mdr1b, Oatp1a5 and Oatp1c1. Conclusions: These results suggests that herbal extracts may play an important role in overcoming the blood brain barrier during pharmacotherapy.

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Cloning, characterization, and expression features of chicken CDS2 splicing variants

10.21203/rs.3.rs-84009/v1 ◽

2020 ◽

Author(s):

Yuanyuan Xu ◽

Shuping Zhang ◽

Yujun Guo ◽

Wen Chen ◽

Yanqun Huang

Keyword(s):

Adipose Tissue ◽

Early Stage ◽

Expression Profiles ◽

Expression Patterns ◽

Mrna Level ◽

Mrna Levels ◽

Exogenous Insulin ◽

Temporal Expression ◽

Spatio Temporal ◽

The Brain

Abstract Background: The CDS gene encodes the CDP-diacylglycerol synthase enzyme that catalyzes the formation of CDP-diacylglycerol (CDP-DAG) from phosphatidic acid. At present, there are no reports of CDS2 in birds. Here, we identified chicken CDS2 transcripts, explored the spatio-temporal expression profiles of total CDS2 and the longest transcript variant CDS2-4, and investigated the effect of exogenous insulin on total the mRNA level of CDS2.Results: Four transcripts of chicken CDS2 (CDS2-1, -2, -3, and -4) were identified, which were alternatively spliced at the 3′-untranslated region (UTR). Chicken CDS2 was located at chr.22, where there was a chromosomal fusion/break event in the evolution of mammals and birds. CDS2 was widely expressed in all tissues examined and the longest variant CDS2-4 was the major transcript. Both total CDS2 and CDS2-4 were prominently expressed in adipose tissue and the heart, and exhibited low expression in the liver and pectoralis of 49 day-old chickens. Quantitative real-time PCR revealed that total CDS2 and CDS2-4 had different spatio-temporal expression patterns in chicken. Total CDS2 exhibited a similar temporal expression tendancy with a high level in the later period of incubation (embryonic day 19 [E19] or 1-day-old) in the brain, liver, and pectoralis. While CDS2-4 presented a distinct temporal expression pattern in these tissues, CDS2-4 levels peaked at 21 days in the brain and pectoralis, while liver CDS2-4 mRNA levels were highest at the early stage of hatching (E10). Total CDS2 (P < 0.001) and CDS2-4 (P = 0.0090) mRNA levels in the liver were differentially regulated throughout development of the chicken. Exogenous insulin significantly downregulated the level of total CDS2 at 240 min in the pectoralis of Silky chickens (P < 0.01). Total CDS2 levels in the liver of Silky chickens were higher than that of the broiler in the basal state and after insulin stimulation.Conclusion: Chicken CDS2 has multiple transcripts with variation at the 3′-UTR, which was prominently expressed in adipose tissue. Total CDS2 and CDS2-4 presented distinct spatio-temporal expression patterns, and they were differentially regulated with age in liver. Insulin could regulate chicken CDS2 levels in a breed- and tissue-specific manner.

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The m6A RNA Modification Quantity and mRNA Expression Level of RNA Methylation-Related Genes in Head and Neck Squamous Cell Carcinoma Cell Lines and Patients

Biomolecules ◽

10.3390/biom11060908 ◽

2021 ◽

Vol 11 (6) ◽

pp. 908

Author(s):

Kamila Romanowska ◽

Agnieszka A. Rawłuszko-Wieczorek ◽

Łukasz Marczak ◽

Agnieszka Kosińska ◽

Wiktoria M. Suchorska ◽

...

Keyword(s):

Mrna Expression ◽

Cell Lines ◽

Mrna Level ◽

Transcript Level ◽

Expression Level ◽

Rna Modification ◽

Mrna Expression Level ◽

Rna Methylation ◽

Carcinoma Cell Lines ◽

Genes Expression

RNA methylation at the nitrogen sixth of adenosine (m6A, N6-methyladenosine) is the most abundant RNA modification which plays a crucial role in all RNA metabolic aspects. Recently, m6A modification has been assigned to mediate the biological processes of cancer cells, but their significance in HNSCC development is still poorly described. Thus, the main aim of this study was to globally quantify m6A modification by the mass spectrometry approach and determine the mRNA expression level of selected m6A RNA methyltransferase (METTL3), demethylase (FTO), and m6A readers (YTHDF2, YTHDC2) in 45 HNSCC patients and 4 cell lines (FaDu, Detroit 562, A-253 and SCC-15) using qPCR. In the results, we have not observed differences in the global amount of m6A modification and the mRNA level of the selected genes between the cancerous and paired-matched histopathologically unchanged tissues from 45 HNSCC patients. However, we have found a positive correlation between selected RNA methylation machinery genes expression and m6A abundance on total RNA and characterized the transcript level of those genes in the HNSCC cell lines. Moreover, the lack of global m6A differences between cancerous and histopathologically unchanged tissues suggests that m6A alterations in specific RNA sites may specifically influence HNSCC tumorigenesis.

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Gene expression analysis in modeling Parkinson’s disease

Nauchno-prakticheskii zhurnal «Medicinskaia genetika» ◽

10.25557/2073-7998.2020.04.103-104 ◽

2020 ◽

pp. 103-104

Author(s):

М.М. Руденок ◽

А.Х. Алиева ◽

А.А. Колачева ◽

М.В. Угрюмов ◽

П.А. Сломинский ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Early Stage ◽

Systemic Disease ◽

Molecular Genetic ◽

Presymptomatic Stage ◽

Whole Transcriptome Analysis ◽

Whole Transcriptome ◽

The Brain ◽

Transcriptome Level

Несмотря на очевидный прогресс, достигнутый в изучении молекулярно-генетических факторов и механизмов патогенеза болезни Паркинсона (БП), в настоящее время стало ясно, что нарушения в структуре ДНК не описывают весь спектр патологических изменений, наблюдаемых при развитии заболевания. В настоящее время показано, что существенное влияние на патогенез БП могут оказывать изменения на уровне транскриптома. В работе были использованы мышиные модели досимптомной стадии БП, поздней досимптомной и ранней симптомной (РСС) стадиями БП. Для полнотранскриптомного анализа пулов РНК тканей черной субстанции и стриатума мозга мышей использовались микрочипы MouseRef-8 v2.0 Expression BeadChip Kit («Illumina», США). Полученные данные указывают на последовательное вовлечение транскриптома в патогенез БП, а также на то, что изменения на транскриптомном уровне процессов транспорта и митохондриального биогенеза могут играть важную роль в нейродегенерации при БП уже на самых ранних этапах. Parkinson’s disease (PD) is a complex systemic disease, mainly associated with the death of dopaminergic neurons. Despite the obvious progress made in the study of molecular genetic factors and mechanisms of PD pathogenesis, it has now become clear that violations in the DNA structure do not describe the entire spectrum of pathological changes observed during the development of the disease. It has now been shown that changes at the transcriptome level can have a significant effect on the pathogenesis of PD. The authors used models of the presymptomatic stage of PD with mice decapitation after 6 hours (6 h-PSS), presymptomatic stage with decapitation after 24 hours (24 h-PSS), advanced presymptomatic (Adv-PSS) and early symptomatic (ESS) stages of PD. For whole transcriptome analysis of RNA pools of the substantia nigra and mouse striatum, the MouseRef-8 v2.0 Expression BeadChip Kit microchips (Illumina, USA) were used. As a result of the analysis of whole transcriptome data, it was shown that, there are a greater number of statistically significant changes in the tissues of the brain and peripheral blood of mice with Adv-PSS and ESS models of PD compared to 6 h-PSS and 24 h-PSS models. In general, the obtained data indicate the sequential involvement of the transcriptome in the pathogenesis of PD, as well as the fact that changes at the transcriptome level of the processes of transport and mitochondrial biogenesis can play an important role in neurodegeneration in PD at an early stage.

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Brain Tumor Detection via Asymmetry Quantification across Mid Sagittal Plane

Recent Advances in Computer Science and Communications ◽

10.2174/2666255813999200831104047 ◽

2020 ◽

Vol 13 ◽

Author(s):

Shoaib Amin Banday ◽

Mohammad Khalid Pandit

Keyword(s):

Brain Tumor ◽

Brain Tumors ◽

Sagittal Plane ◽

Early Stage ◽

Imaging Techniques ◽

Complex Structure ◽

Magnetic Resonance Images ◽

Absolute Difference ◽

Brain Hemispheres ◽

The Brain

Introduction: Brain tumor is among the major causes of morbidity and mortality rates worldwide. According to National Brain Tumor Foundation (NBTS), the death rate has nearly increased by as much as 300% over last couple of decades. Tumors can be categorized as benign (non-cancerous) and malignant (cancerous). The type of the brain tumor significantly depends on various factors like the site of its occurrence, its shape, the age of the subject etc. On the other hand, Computer Aided Detection (CAD) has been improving significantly in recent times. The concept, design and implementation of these systems ascend from fairly simple ones to computationally intense ones. For efficient and effective diagnosis and treatment plans in brain tumor studies, it is imperative that an abnormality is detected at an early stage as it provides a little more time for medical professionals to respond. The early detection of diseases has predominantly been possible because of medical imaging techniques developed from past many decades like CT, MRI, PET, SPECT, FMRI etc. The detection of brain tumors however, has always been a challenging task because of the complex structure of the brain, diverse tumor sizes and locations in the brain. Method: This paper proposes an algorithm that can detect the brain tumors in the presence of the Radio-Frequency (RF) inhomoginiety. The algorithm utilizes the Mid Sagittal Plane as a landmark point across which the asymmetry between the two brain hemispheres is estimated using various intensity and texture based parameters. Result: The results show the efficacy of the proposed method for the detection of the brain tumors with an acceptable detection rate. Conclusion: In this paper, we have calculated three textural features from the two hemispheres of the brain viz: Contrast (CON), Entropy (ENT) and Homogeneity (HOM) and three parameters viz: Root Mean Square Error (RMSE), Correlation Co-efficient (CC), and Integral of Absolute Difference (IAD) from the intensity distribution profiles of the two brain hemispheres to predict any presence of the pathology. First a Mid Sagittal Plane (MSP) is obtained on the Magnetic Resonance Images that virtually divides brain into two bilaterally symmetric hemispheres. The block wise texture asymmetry is estimated for these hemispheres using the above 6 parameters.

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Miniaturization and Automation of a Human In Vitro Blood–Brain Barrier Model for the High-Throughput Screening of Compounds in the Early Stage of Drug Discovery

Pharmaceutics ◽

10.3390/pharmaceutics13060892 ◽

2021 ◽

Vol 13 (6) ◽

pp. 892

Author(s):

Elisa L. J. Moya ◽

Elodie Vandenhaute ◽

Eleonora Rizzi ◽

Marie-Christine Boucau ◽

Johan Hachani ◽

...

Keyword(s):

Drug Discovery ◽

Blood Brain Barrier ◽

Early Stage ◽

Molecular Transport ◽

Brain Barrier ◽

Blood Brain ◽

Cns Drugs ◽

The Impact ◽

The Brain

Central nervous system (CNS) diseases are one of the top causes of death worldwide. As there is a difficulty of drug penetration into the brain due to the blood–brain barrier (BBB), many CNS drugs treatments fail in clinical trials. Hence, there is a need to develop effective CNS drugs following strategies for delivery to the brain by better selecting them as early as possible during the drug discovery process. The use of in vitro BBB models has proved useful to evaluate the impact of drugs/compounds toxicity, BBB permeation rates and molecular transport mechanisms within the brain cells in academic research and early-stage drug discovery. However, these studies that require biological material (animal brain or human cells) are time-consuming and involve costly amounts of materials and plastic wastes due to the format of the models. Hence, to adapt to the high yields needed in early-stage drug discoveries for compound screenings, a patented well-established human in vitro BBB model was miniaturized and automated into a 96-well format. This replicate met all the BBB model reliability criteria to get predictive results, allowing a significant reduction in biological materials, waste and a higher screening capacity for being extensively used during early-stage drug discovery studies.

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AHR-dependent genes and response to MTX therapy in rheumatoid arthritis patients

The Pharmacogenomics Journal ◽

10.1038/s41397-021-00238-4 ◽

2021 ◽

Author(s):

Anna Wajda ◽

Ewa Walczuk ◽

Barbara Stypińska ◽

Jakub Lach ◽

Danat Yermakovich ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Lymphoblastic Leukemia ◽

Mrna Level ◽

Poor Response ◽

Evolutionary Analysis ◽

First Line ◽

Aryl Hydrocarbon ◽

First Line Therapy ◽

Genes Expression ◽

Ahr Gene

AbstractMethotrexate (MTX) is the first-line therapy for rheumatoid arthritis. Nevertheless, MTX resistance is quite a common issue in clinical practice. There are some premises that aryl hydrocarbon receptor (AhR) gene battery may take part in MTX metabolism. In the present retrospective study, we analyzed genes expression of AHR genes battery associated with MTX metabolism in whole blood of RA patients with good and poor response to MTX treatment. Additionally, sequencing, genotyping and bioinformatics analysis of AHR repressor gene (AHRR) c.565C > G (rs2292596) and c.1933G > C (rs34453673) have been performed. Theoretically, both changes may have an impact on H3K36me3 and H3K27me3. Evolutionary analysis revealed that rs2292596 may be possibly damaging. Allele G in rs2292596 and DAS28 seems to be associated with a higher risk of poor response to MTX treatment in RA. RA patients with poor response to MTX treatment revealed upregulated AhR and SLC19A1 mRNA level. Treatment with IL-6 inhibitor may be helpful to overcome the low-dose MTX resistance. Analysis of gene expression revealed possible another cause of poor response to MTX treatment which is different from that observed in the case of acute lymphoblastic leukemia.

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Regulation of mdr2 P-glycoprotein expression by bile salts

Biochemical Journal ◽

10.1042/bj3210389 ◽

1997 ◽

Vol 321 (2) ◽

pp. 389-395 ◽

Cited By ~ 39

Author(s):

Charles M. G. FRIJTERS ◽

Roelof OTTENHOFF ◽

Michel J. A. van WIJLAND ◽

Carin M. J. van NIEUWKERK ◽

Albert K. GROEN ◽

...

Keyword(s):

Bile Salt ◽

Bile Salts ◽

Control Diet ◽

Mrna Level ◽

Northern Blotting ◽

Mrna Levels ◽

Male Mice ◽

Complete Replacement ◽

P Glycoprotein ◽

Mrna Content

The phosphatidyl translocating activity of the mdr2 P-glycoprotein (Pgp) in the canalicular membrane of the mouse hepatocyte is a rate-controlling step in the biliary secretion of phospholipid. Since bile salts also regulate the secretion of biliary lipids, we investigated the influence of the type of bile salt in the circulation on mdr2 Pgp expression and activity. Male mice were fed a purified diet to which either 0.1% (w/w) cholate or 0.5% (w/w) ursodeoxycholate was added. This led to a near-complete replacement of the endogenous bile salt pool (mainly tauromuricholate) by taurocholate or tauroursodeoxycholate respectively. The phospholipid secretion capacity was then determined by infusion of increasing amounts of tauroursodeoxycholate. Cholate feeding resulted in a 55% increase in maximal phospholipid secretion compared with that in mice on the control diet. Northern blotting revealed that cholate feeding increased mdr2 Pgp mRNA levels by 42%. Feeding with ursodeoxycholate did not influence the maximum rate of phospholipid output or the mdr2 mRNA content. Female mice had a higher basal mdr2 Pgp mRNA level than male mice, and this was also correlated with a higher phospholipid secretion capacity. This could be explained by the 4-fold higher basal cholate content in the bile of female compared with male mice. Our results suggest that the type of bile salts in the circulation influences the expression of the mdr2 gene.

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