scholarly journals Restraint Stress in Mice Alters Set of 25 miRNAs Which Regulate Stress- and Depression-Related mRNAs

2020 ◽  
Vol 21 (24) ◽  
pp. 9469
Author(s):  
Joanna Solich ◽  
Maciej Kuśmider ◽  
Agata Faron-Górecka ◽  
Paulina Pabian ◽  
Marta Dziedzicka-Wasylewska
Keyword(s):  
Machine Learning ◽  
Restraint Stress ◽  
Molecular Level ◽  
Norepinephrine Transporter ◽  
Mouse Serum ◽  
Control Group ◽  
Gene Encoding ◽  
Knock Out ◽  
Differentially Expressed Mirnas ◽  
Mirnas Expression

In the present study, we aim to identify the effect of restrain stress (RS) on the expression of miRNAs in mouse serum. We used three genotypes of animals (mice with knock-out of the gene-encoding norepinephrine transporter, NET-KO; C57BL/6J, and SWR/J) which had previously been shown to display different sensitivity to RS, and focused on miRNAs which were altered by RS in the serum of all three genotypes. An analysis of miRNAs expression allowed for the identification of a set of 25 differentially expressed miRNAs; 10 were down-regulated compared to an appropriate control group of animals, while 15 were up-regulated. The application of DIANA-miRPath v. 3.0 allowed for the identification of selected pathways (KEGG) and Gene Ontology (GO) categories that were significantly controlled by these miRNAs, while miRWalk v. 3.0—the platform that used the machine learning based algorithm, TaRPmiR—was used to find their targets. The results indicate that 25 miRNAs, identified as altered upon RS in three genotypes of mice, are responsible for regulation of mRNA-encoding proteins that are key for the main hypotheses of depression; therefore, they may help to understand the link between stress and depression at the molecular level.

Genome-wide analysis of microRNAs expression profiling in patients with primary IgA nephropathy

Genome ◽  
2013 ◽  
Vol 56 (3) ◽  
pp. 161-169 ◽  
Author(s):  
Kuibi Tan ◽  
Jing Chen ◽  
Wuxian Li ◽  
Yuyu Chen ◽  
Weiguo Sui ◽  
...  
Keyword(s):  
High Throughput Sequencing ◽  
Target Genes ◽  
Immunoglobulin A ◽  
Differentially Expressed ◽  
Control Group ◽  
Pathological Changes ◽  
Genome Wide ◽  
Differentially Expressed Mirnas ◽  
Specific Tissue ◽  
Mirnas Expression

The aim of this study was to investigate the differential expression characteristics and the roles of the genome-wide microRNAs (miRNAs) in immunoglobulin A nephropathy (IgAN) kidney tissues. We used Illumina high-throughput sequencing technology to evaluate the miRNAs expression of six biopsy tissues from IgAN and six normal renal cortex specimens from patients with renal cell carcinoma. We observed a total of 85 miRNAs that were differentially expressed in the six IgAN patients, of which 11 miRNAs were up-regulated and 74 miRNAs were down-regulated in patients' tissues compared with control tissues. Additionally, we identified 55 candidate novel miRNAs in our study, which comprised seven candidates who were detected in the IgAN group and 49 candidates who were detected in the control group. Only one candidate (miR-n-9) was expressed in both groups. The bioinformatics showed that the regulated target genes of differentially expressed miRNAs were associated with immune and renal pathological changes. The identification of specific tissue miRNAs in our study not only helped clarify the genetics or immunology mechanisms involved in the pathogenesis of IgAN but also helped explain the pathological changes in the kidney tissues. We hypothesize that some significant miRNAs might potentially serve as novel diagnostic biomarkers in IgAN patients.

Preliminary Study of microRNAs Allele-Specific Targeting in Allergic Rhinitis Patients from Central China

2021 ◽  
Vol 24 ◽  
Author(s):  
Yu-Qin Deng ◽  
Song Li ◽  
Zheng-Yan Liang ◽  
Fen Li ◽  
Si-Lu Wen ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Nasal Mucosa ◽  
Central China ◽  
Differentially Expressed ◽  
Control Group ◽  
Sequencing Analysis ◽  
Rt Pcr ◽  
Altered Expression ◽  
Differentially Expressed Mirnas ◽  
Mirnas Expression

Background: Abnormal expression of miRNA is a common feature in many diseases. Some studies have also emphasized that miRNAs play an important role in asthma and allergic rhinitis (AR). This study attempts to reveal the differences between miRNAs expression and normal nasal mucosa in AR patients by microarray method, so as to further understand the molecular mechanism of AR development. Method: MiRNA microrrays were used for analyzing six samples of the nasal mucosa of AR and six samples of nonallergic patients. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) of some differentially expressed miRNAs was used to confirm the array results. Furthermore, pathway analysis was carried out. Results: The microarray identified that 64 miRNAs exhibited altered expression in the nasal mucosa of the AR group when compared with the control group. Moreover, the expression levels of ten miRNAs were significantly altered in the AR group. To verify the results of the microarray, three differentially expressed miRNA were determined by RT-PCR, and the results also confirmed these changes. Ten differentially expressed miRNAs were present in the nasal mucosa of AR patients compared with the control group, and three differentially expressed miRNAs, as miR-1244, miR-4651 and miR-7641, were determined by RT-PCR, indicating that they play important roles in the process of AR. Conclusion: miR-1244, miR-4651 and miR-7641 may play important roles in the process of AR. Sequencing analysis indicated that three kinds of mutations exist in MAPK8 3’UTR, which may play a role in binding with miR-7641, and then influence the AR process. Single miRNA or, more probably, their sets hold the promise for their use as biomarkers of allergic rhinitis. They may also be promising targets in future therapies.

scholarly journals Analysis of Risk Factors in Dementia Through Machine Learning

2020 ◽  
pp. 1-17
Author(s):  
Francisco Javier Balea-Fernandez ◽  
Beatriz Martinez-Vega ◽  
Samuel Ortega ◽  
Himar Fabelo ◽  
Raquel Leon ◽  
...  
Keyword(s):  
Machine Learning ◽  
Optimization Algorithms ◽  
Progressive Increase ◽  
Control Group ◽  
Data Sets ◽  
Modifiable Factors ◽  
Validation Set ◽  
The One ◽  
And Control ◽  
Potential Tool

Background: Sociodemographic data indicate the progressive increase in life expectancy and the prevalence of Alzheimer’s disease (AD). AD is raised as one of the greatest public health problems. Its etiology is twofold: on the one hand, non-modifiable factors and on the other, modifiable. Objective: This study aims to develop a processing framework based on machine learning (ML) and optimization algorithms to study sociodemographic, clinical, and analytical variables, selecting the best combination among them for an accurate discrimination between controls and subjects with major neurocognitive disorder (MNCD). Methods: This research is based on an observational-analytical design. Two research groups were established: MNCD group (n = 46) and control group (n = 38). ML and optimization algorithms were employed to automatically diagnose MNCD. Results: Twelve out of 37 variables were identified in the validation set as the most relevant for MNCD diagnosis. Sensitivity of 100%and specificity of 71%were achieved using a Random Forest classifier. Conclusion: ML is a potential tool for automatic prediction of MNCD which can be applied to relatively small preclinical and clinical data sets. These results can be interpreted to support the influence of the environment on the development of AD.

scholarly journals Estimating Causal Effects When the Treatment Affects All Subjects Simultaneously: An Application

2021 ◽  
Vol 5 (2) ◽  
pp. 22
Author(s):  
Chiara Binelli
Keyword(s):  
Machine Learning ◽  
Carbon Dioxide ◽  
Global Warming ◽  
Carbon Dioxide Emissions ◽  
Control Group ◽  
Sources Of Information ◽  
Average Global Temperature ◽  
Causal Impact ◽  
The Impact ◽  
Robust Evidence

Several important questions cannot be answered with the standard toolkit of causal inference since all subjects are treated for a given period and thus there is no control group. One example of this type of questions is the impact of carbon dioxide emissions on global warming. In this paper, we address this question using a machine learning method, which allows estimating causal impacts in settings when a randomized experiment is not feasible. We discuss the conditions under which this method can identify a causal impact, and we find that carbon dioxide emissions are responsible for an increase in average global temperature of about 0.3 degrees Celsius between 1961 and 2011. We offer two main contributions. First, we provide one additional application of Machine Learning to answer causal questions of policy relevance. Second, by applying a methodology that relies on few directly testable assumptions and is easy to replicate, we provide robust evidence of the man-made nature of global warming, which could reduce incentives to turn to biased sources of information that fuels climate change skepticism.

scholarly journals Lack of WWC2 Protein Leads to Aberrant Angiogenesis in Postnatal Mice

2021 ◽  
Vol 22 (10) ◽  
pp. 5321
Author(s):  
Viktoria Constanze Brücher ◽  
Charlotte Egbring ◽  
Tanja Plagemann ◽  
Pavel I. Nedvetsky ◽  
Verena Höffken ◽  
...  
Keyword(s):  
Signalling Pathway ◽  
Control Group ◽  
Knock Out ◽  
Ocular Angiogenesis ◽  
Sprouting Angiogenesis ◽  
Adult Mice ◽  
Upstream Regulator ◽  
Knock Out Mice ◽  
Hippo Signalling

The WWC protein family is an upstream regulator of the Hippo signalling pathway that is involved in many cellular processes. We examined the effect of an endothelium-specific WWC1 and/or WWC2 knock-out on ocular angiogenesis. Knock-outs were induced in C57BL/6 mice at the age of one day (P1) and evaluated at P6 (postnatal mice) or induced at the age of five weeks and evaluated at three months of age (adult mice). We analysed morphology of retinal vasculature in retinal flat mounts. In addition, in vivo imaging and functional testing by electroretinography were performed in adult mice. Adult WWC1/2 double knock-out mice differed neither functionally nor morphologically from the control group. In contrast, the retinas of the postnatal WWC knock-out mice showed a hyperproliferative phenotype with significantly enlarged areas of sprouting angiogenesis and a higher number of tip cells. The branching and end points in the peripheral plexus were significantly increased compared to the control group. The deletion of the WWC2 gene was decisive for these effects; while knocking out WWC1 showed no significant differences. The results hint strongly that WWC2 is an essential regulator of ocular angiogenesis in mice. As an activator of the Hippo signalling pathway, it prevents excessive proliferation during physiological angiogenesis. In adult animals, WWC proteins do not seem to be important for the maintenance of the mature vascular plexus.

scholarly journals Effects of Electroacupuncture on Pain Threshold of Laboring Rats and the Expression of Norepinephrine Transporter andα2 Adrenergic Receptor in the Central Nervous System

2016 ◽  
Vol 2016 ◽  
pp. 1-8
Author(s):  
Qianli Tang ◽  
Qiuyan Jiang ◽  
Suren R. Sooranna ◽  
Shike Lin ◽  
Yuanyuan Feng ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Adrenergic Receptor ◽  
Pain Threshold ◽  
Norepinephrine Transporter ◽  
Control Group ◽  
Tail Flick ◽  
Pregnant Rats ◽  
Tail Flick Test ◽  
The Central Nervous System

To observe the effects of electroacupuncture on pain threshold of laboring rats and the expression of norepinephrine transporter andα2 adrenergic receptor in the central nervous system to determine the mechanism of the analgesic effect of labor. 120 pregnant rats were divided into 6 groups: a control group, 4 electroacupuncture groups, and a meperidine group. After interventions, the warm water tail-flick test was used to observe pain threshold. NE levels in serum, NET, andα2AR mRNA and protein expression levels in the central nervous system were measured. No difference in pain threshold was observed between the 6 groups before intervention. After intervention, increased pain thresholds were observed in all groups except the control group with a higher threshold seen in the electroacupuncture groups. Serum NE levels decreased in the electroacupuncture and MP groups. Increases in NET andα2AR expression in the cerebral cortex and decreases in enlarged segments of the spinal cord were seen. Acupuncture increases uptake of NE via cerebral NET and decreases its uptake by spinal NET. The levels ofα2AR are also increased and decreased, respectively, in both tissues. This results in a decrease in systemic NE levels and may be the mechanism for its analgesic effects.

scholarly journals Rare Variant in the SLC6A2 Encoding a Norepinephrine Transporter Is Associated with Elite Athletic Performance in the Polish Population

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 919
Author(s):  
Jakub P. Fichna ◽  
Kinga Humińska-Lisowska ◽  
Krzysztof Safranow ◽  
Jakub G. Adamczyk ◽  
Paweł Cięszczyk ◽  
...  
Keyword(s):  
Athletic Performance ◽  
Genetic Variants ◽  
Pain Perception ◽  
Association Studies ◽  
Genetic Association Studies ◽  
Norepinephrine Transporter ◽  
Control Group ◽  
Brain Functioning ◽  
Mental Abilities ◽  
Functional Analyses

Numerous genetic factors have been shown to influence athletic performance, but the list is far from comprehensive. In this study, we analyzed genetic variants in two genes related to mental abilities, SLC6A2 (rs1805065) and SYNE1 (rs2635438) in a group of 890 athletes (320 endurance, 265 power, and 305 combat athletes) vs. 1009 sedentary controls. Genotyping of selected SNPs was performed using TaqMan SNP genotyping assays. SLC6A2 codes for norepinephrine transporter, a protein involved in modulating mood, arousal, memory, learning, and pain perception, while SYNE1 encodes protein important for the maintenance of the cerebellum—the part of the brain that coordinates complex body movements. Both SNPs (rs2635438 and rs1805065) showed no statistically significant differences between the frequencies of variants in the athletes and the sedentary controls (athletes vs. control group) or in the athlete subgroups (martial vs. control, endurance vs. control, and power vs. control). The rs1805065 T variant of SLC6A2 was found to be overrepresented in male high-elite martial sports athletes when compared to sedentary controls (OR = 6.56, 95%CI = 1.82–23.59, p = 0.010). This supports the hypothesis that genetic variants potentially affecting brain functioning can influence elite athletic performance and indicate the need for further genetic association studies, as well as functional analyses.

Age-associated features of the expression level of apoptosis markers in cardiomyocytes of patients with dilated cardiomyopathy

2022 ◽  
pp. 885-890
Author(s):  
К.П. Кравченко ◽  
К. Л. Козлов ◽  
А.О. Дробинцева ◽  
Д.С. Медведев ◽  
В.О. Полякова
Keyword(s):  
Cell Death ◽  
Dilated Cardiomyopathy ◽  
Molecular Mechanisms ◽  
Molecular Level ◽  
Confocal Laser ◽  
Control Group ◽  
Cellular Mechanisms ◽  
Apoptosis Pathway ◽  
Bax Protein

Для понимания патогенеза дилатационной кардиомиопатии (ДКМП) необходимо установить молекулярно-клеточные механизмы старения миокарда, в том числе связанные с программируемой клеточной гибелью, молекулярные механизмы которого практически не изучены. Цель работы - изучение маркеров апоптоза в кардиомиоцитах у пациентов с ДКМП in vitro. В работе использовали метод первичных диссоциированных клеточных культур и метод иммунофлюоресцентной конфокальной лазерной микроскопии. Для моделирования клеточного старения использовали клетки 3-го и 14-го пассажей, соответствующие «молодым» и «старым» культурам. На молекулярном уровне старение клеток кардиомиоцитов сопровождалось повышением экспрессии р16 в 2 раза по сравнению с «молодыми культурами» как в контрольной, так и в группе с ДКМП. Также установлено, что экспрессия р16 в культурах, взятых от пациентов с патологией, была в 2 раза выше, чем в аналогичных культурах от здоровых пациентов. Экспрессия р21 была повышена в группе с ДКМП по сравнению с контрольной группой, однако при старении культуры экспрессия p21 не изменялась, оставаясь на высоком уровне. Наиболее значимые различия были получены при сравнении экспрессии Bax в культуре клеток кардиомиоцитов из группы с ДКМП в «молодой» культуре с нормой - в 3,2 раза. Старение клеток миокарда на молекулярном уровне проявлялось в повышении экспрессии белка Baх, именно он является запускающим механизмом митохондриального пути апоптоза. Возможно, этот путь клеточной гибели является превалирующем при ДКМП. To understand the pathogenesis of dilated cardiomyopathy (DCMP), it is necessary to establish the molecular-cellular mechanisms of myocardial aging, including those associated with programmed cell death, the molecular mechanisms of which have not been practically studied. The aim of this work is to study markers of apoptosis in cardiomyocytes of patients with DCMP in vitro. We used the method of primary dissociated cell cultures and the method of immunofluorescence confocal laser microscopy. Cells of the 3 and 14 passages, corresponding to «young» and «old» cultures, were used to simulate cellular senescence. Results. At the molecular level, aging of cardiomyocyte cells was accompanied by a twofold increase in the expression of p16 compared to «young cultures» both in the control group and in the group with DCMP. It was also found that the expression of p16 in cultures taken from patients with pathology was 2 times higher than in similar cultures from healthy patients. The expression of p21 was increased in the group with DCMP compared to the control; however, with aging of the culture, the expression of p21 did not change, remaining at a significant level. The most significant differences were obtained when comparing the expression of Bax in the cell culture of cardiomyocytes from the group with DCMP in a «young» culture compared with the norm, 3,2 times. Aging of myocardial cells at the molecular level was manifested in an increase in the expression of the Bax protein, which is the triggering mechanism of the mitochondrial apoptosis pathway. It is possible that this pathway of cell death is prevalent in DCMP.

scholarly journals CD77 levels over enzyme replacement treatment in Fabry Disease Family (V269M)

2018 ◽  
Vol 40 (4) ◽  
pp. 333-338
Author(s):  
Ester Miranda Pereira ◽  
Adalberto Socorro da Silva ◽  
Raimundo Nonato da Silva ◽  
José Tiburcio Monte Neto ◽  
Fernando F. do Nascimento ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Cell Types ◽  
Control Group ◽  
Gene Encoding ◽  
Peripheral Blood Mononuclear ◽  
Enzyme Replacement ◽  
Replacement Treatment ◽  
Promising Tool ◽  
Potential Marker ◽  
Different Cell Types

ABSTRACT Introduction: Fabry disease (FD) is a disorder caused by mutations in the gene encoding for lysosomal enzyme α-galactosidase A (α-GAL). Reduced α-GAL activity leads to progressive accumulation of globotriaosylceramide (Gb3), also known as CD77. The recent report of increased expression of CD77 in blood cells of patients with FD indicated that this molecule can be used as a potential marker for monitoring enzyme replacement therapy (ERT). Objective: The purpose of this study was to evaluate the CD77 levels throughout ERT in FD patients (V269M mutation). Methods: We evaluated the fluctuations in PBMC (peripheral blood mononuclear cell) membrane CD77 expression in FD patients undergoing ERT and correlated these levels with those observed in different cell types. Results: A greater CD77 expression was found in phagocytes of patients compared to controls at baseline. Interestingly, the variability in CD77 levels is larger in patients at baseline (340 - 1619 MIF) and after 12 months of ERT (240 - 530 MIF) compared with the control group (131 - 331 MFI). Furthermore, by analyzing the levels of CD77 in phagocytes from patients throughout ERT, we found a constant decrease in CD77 levels. Conclusion: The increased CD77 levels in the phagocytes of Fabry carriers together with the decrease in CD77 levels throughout ERT suggest that measuring CD77 levels in phagocytes is a promising tool for monitoring the response to ERT in FD.

scholarly journals Exposure to 3′Sialyllactose-Poor Milk during Lactation Impairs Cognitive Capabilities in Adulthood

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4191
Author(s):  
Edoardo Pisa ◽  
Alberto Martire ◽  
Valentina Chiodi ◽  
Alice Traversa ◽  
Viviana Caputo ◽  
...  
Keyword(s):  
Cognitive Functions ◽  
Selective Reduction ◽  
Long Term Potentiation ◽  
Control Group ◽  
Preclinical Model ◽  
Knock Out ◽  
Cognitive Domains ◽  
Memory And Attention ◽  
Term Potentiation ◽  
Regulatory Functions

Breast milk exerts pivotal regulatory functions early in development whereby it contributes to the maturation of brain and associated cognitive functions. However, the specific components of maternal milk mediating this process have remained elusive. Sialylated human milk oligosaccharides (HMOs) represent likely candidates since they constitute the principal neonatal dietary source of sialic acid, which is crucial for brain development and neuronal patterning. We hypothesize that the selective neonatal lactational deprivation of a specific sialylated HMOs, sialyl(alpha2,3)lactose (3′SL), may impair cognitive capabilities (attention, cognitive flexibility, and memory) in adulthood in a preclinical model. To operationalize this hypothesis, we cross-fostered wild-type (WT) mouse pups to B6.129-St3gal4tm1.1Jxm/J dams, knock-out (KO) for the gene synthesizing 3′SL, thereby providing milk with approximately 80% 3′SL content reduction. We thus exposed lactating WT pups to a selective reduction of 3′SL and investigated multiple cognitive domains (including memory and attention) in adulthood. Furthermore, to account for the underlying electrophysiological correlates, we investigated hippocampal long-term potentiation (LTP). Neonatal access to 3′SL-poor milk resulted in decreased attention, spatial and working memory, and altered LTP compared to the control group. These results support the hypothesis that early-life dietary sialylated HMOs exert a long-lasting role in the development of cognitive functions.

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