scholarly journals Molecular Characterisation of Canine Osteosarcoma in High Risk Breeds

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2405
Author(s):  
Siobhan Simpson ◽  
Mark Dunning ◽  
Simone de Brot ◽  
Aziza Alibhai ◽  
Clara Bailey ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Risk ◽  
Molecular Mechanisms ◽  
Disease Process ◽  
Fragment Analysis ◽  
Nuclear Receptor Coactivator ◽  
Polymerase Chain ◽  
Cure Rates ◽  
Gene Ontologies ◽  
Polyq Tract

Dogs develop osteosarcoma (OSA) and the disease process closely resembles that of human OSA. OSA has a poor prognosis in both species and disease-free intervals and cure rates have not improved in recent years. Gene expression in canine OSAs was compared with non-tumor tissue utilising RNA sequencing, validated by qRT-PCR and immunohistochemistry (n = 16). Polymorphic polyglutamine (polyQ) tracts in the androgen receptor (AR/NR3C4) and nuclear receptor coactivator 3 (NCOA3) genes were investigated in control and OSA patients using polymerase chain reaction (PCR), Sanger sequencing and fragment analysis (n = 1019 Rottweilers, 379 Irish Wolfhounds). Our analysis identified 1281 significantly differentially expressed genes (>2 fold change, p < 0.05), specifically 839 lower and 442 elevated gene expression in osteosarcoma (n = 3) samples relative to non-malignant (n = 4) bone. Enriched pathways and gene ontologies were identified, which provide insight into the molecular pathways implicated in canine OSA. Expression of a subset of these genes (SLC2A1, DKK3, MMP3, POSTN, RBP4, ASPN) was validated by qRTPCR and immunohistochemistry (MMP3, DKK3, SLC2A1) respectively. While little variation was found in the NCOA3 polyQ tract, greater variation was present in both polyQ tracts in the AR, but no significant associations in length were made with OSA. The data provides novel insights into the molecular mechanisms of OSA in high risk breeds. This knowledge may inform development of new prevention strategies and treatments for OSA in dogs and supports utilising spontaneous OSA in dogs to improve understanding of the disease in people.

scholarly journals Small Molecule, Big Prospects: MicroRNA in Pregnancy and Its Complications

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Meng Cai ◽  
Gopi K. Kolluru ◽  
Asif Ahmed
Keyword(s):  
Gene Expression ◽  
Preterm Labor ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Regulation Of Gene Expression ◽  
Disease Process ◽  
Rna Molecules ◽  
Small Noncoding Rna ◽  
Posttranscriptional Level ◽  
In Pregnancy

MicroRNAs are small, noncoding RNA molecules that regulate target gene expression in the posttranscriptional level. Unlike siRNA, microRNAs are “fine-tuners” rather than “switches” in the regulation of gene expression; thus they play key roles in maintaining tissue homeostasis. The aberrant microRNA expression is implicated in the disease process. To date, numerous studies have demonstrated the regulatory roles of microRNAs in various pathophysiological conditions. In contrast, the study of microRNA in pregnancy and its associated complications, such as preeclampsia (PE), fetal growth restriction (FGR), and preterm labor, is a young field. Over the last decade, the knowledge of pregnancy-related microRNAs has increased and the molecular mechanisms by which microRNAs regulate pregnancy or its associated complications are emerging. In this review, we focus on the recent advances in the research of pregnancy-related microRNAs, especially their function in pregnancy-associated complications and the potential clinical applications. Here microRNAs that associate with pregnancy are classified as placenta-specific, placenta-associated, placenta-derived circulating, and uterine microRNA according to their localization and origin. MicroRNAs offer a great potential for developing diagnostic and therapeutic targets in pregnancy-related disorders.

scholarly journals Gene Expression Profiling in Perilesional and Contralateral Areas after Ischemia in Rat Brain

2002 ◽  
Vol 22 (2) ◽  
pp. 153-160 ◽  
Author(s):  
Kathy Keyvani ◽  
Otto W. Witte ◽  
Werner Paulus
Keyword(s):  
Gene Expression ◽  
Somatosensory Cortex ◽  
Metabolic Pathways ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Taqman Assay ◽  
Adult Rats ◽  
Functional Reorganization ◽  
Polymerase Chain ◽  
Dna Macroarrays

Structural and functional reorganization in the vicinity of damaged neocortex and other connected brain areas seems to be responsible for postlesional functional recovery. To better understand the molecular mechanisms underlying this type of plasticity, gene expression patterns were analyzed by using DNA macroarrays comprising 1176 genes. Circumscribed unilateral infarcts consistently affecting the forelimb area of the motor cortex were induced photochemically in adult rats. Ten days after lesioning, cortical gene expression fingerprints were evaluated from an area adjacent to the lesion as well as two contralateral areas of motor and somatosensory cortex. Discrete regions showed distinct expression patterns. Upregulation was observed of different members of transcription factors, immediate early genes, neuronal signaling as well as neuronal growth and structure-associated genes, ipsilaterally (six genes) and/or contralaterally (eight genes in the motor and seven in the somatosensory cortex). In contrast, downregulations were restricted to ipsilateral areas and included genes coding for ion channels, transport proteins, mediators of metabolic pathways, and intracellular transducers (14 genes). A subset of these regulations were further confirmed by real-time polymerase chain reaction (TaqMan assay). At least part of the detected regulations, in particular those of the contralateral hemisphere, are likely to underlie plasticity processes.

Differential display competitive polymerase chain reaction: An optimal tool for assaying gene expression

1999 ◽  
Vol 20 (2) ◽  
pp. 230 ◽  
Author(s):  
Marianne Jorgensen ◽  
Maja Bévort ◽  
Thuri S. Kledal ◽  
Brian V. Hansen ◽  
Marlene Dalgaard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Polymerase Chain Reaction ◽  
Differential Display ◽  
Chain Reaction ◽  
Competitive Polymerase Chain Reaction ◽  
Polymerase Chain

The Mechanisms Behind the Biological Activity of Flavonoids

2019 ◽  
Vol 26 (39) ◽  
pp. 6976-6990 ◽  
Author(s):  
Ana María González-Paramás ◽  
Begoña Ayuda-Durán ◽  
Sofía Martínez ◽  
Susana González-Manzano ◽  
Celestino Santos-Buelga
Keyword(s):  
Gene Expression ◽  
Biological Activity ◽  
Phenolic Compounds ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Radical Scavenging ◽  
Model Organism ◽  
Stress Theory ◽  
Radical Scavenging Properties

: Flavonoids are phenolic compounds widely distributed in the human diet. Their intake has been associated with a decreased risk of different diseases such as cancer, immune dysfunction or coronary heart disease. However, the knowledge about the mechanisms behind their in vivo activity is limited and still under discussion. For years, their bioactivity was associated with the direct antioxidant and radical scavenging properties of phenolic compounds, but nowadays this assumption is unlikely to explain their putative health effects, or at least to be the only explanation for them. New hypotheses about possible mechanisms have been postulated, including the influence of the interaction of polyphenols and gut microbiota and also the possibility that flavonoids or their metabolites could modify gene expression or act as potential modulators of intracellular signaling cascades. This paper reviews all these topics, from the classical view as antioxidants in the context of the Oxidative Stress theory to the most recent tendencies related with the modulation of redox signaling pathways, modification of gene expression or interactions with the intestinal microbiota. The use of C. elegans as a model organism for the study of the molecular mechanisms involved in biological activity of flavonoids is also discussed.

Neuroblastoma: An Updated Review on Biology and Treatment

2020 ◽  
Vol 20 (13) ◽  
pp. 1014-1022 ◽  
Author(s):  
Suresh Mallepalli ◽  
Manoj Kumar Gupta ◽  
Ramakrishna Vadde
Keyword(s):  
Survival Rate ◽  
High Risk ◽  
Molecular Mechanisms ◽  
Definitive Treatment ◽  
Therapeutic Drug ◽  
Mycn Amplification ◽  
Dependent Manner ◽  
High Risk Patients ◽  
Treatment And Prevention ◽  
Risk Patients

Background: Neuroblastoma (NB) is the second leading extracranial solid tumors of early childhood and clinically characterized by the presence of round, small, monomorphic cells with excess nuclear pigmentation (hyperchromasia).Owing to a lack of definitive treatment against NB and less survival rate in high-risk patients, there is an urgent requirement to understand molecular mechanisms associated with NB in a better way, which in turn can be utilized for developing drugs towards the treatment of NB in human. Objectives: In this review, an approach was adopted to understand major risk factors, pathophysiology, the molecular mechanism associated with NB, and various therapeutic agents that can serve as drugs towards the treatment of NB in humans. Conclusions: Numerous genetic (e.g., MYCN amplification), perinatal, and gestational factors are responsible for developing NB. However, no definite environmental or parental exposures responsible for causing NB have been confirmed to date. Though intensive multimodal treatment approaches, namely, chemotherapy, surgery &radiation, may help in improving the survival rate in children, these approaches have several side effects and do not work efficiently in high-risk patients. However, recent studies suggested that numerous phytochemicals, namely, vincristine, and matrine have a minimal side effect in the human body and may serve as a therapeutic drug during the treatment of NB. Most of these phytochemicals work in a dose-dependent manner and hence must be prescribed very cautiously. The information discussed in the present review will be useful in the drug discovery process as well as treatment and prevention on NB in humans.

Relative Expression of Mouse Udp-glucuronosyl Transferase 2b1 Gene in the Livers, Kidneys, and Hearts: The Influence of Nonsteroidal Anti-inflammatory Drug Treatment

2019 ◽  
Vol 20 (11) ◽  
pp. 918-923 ◽  
Author(s):  
Yazun Jarrar ◽  
Qais Jarrar ◽  
Mohammad Abu-Shalhoob ◽  
Abdulqader abed ◽  
Esra'a Sha'ban
Keyword(s):  
Gene Expression ◽  
Strongly Correlated ◽  
Chain Reaction ◽  
Inflammatory Drug ◽  
Relative Expression ◽  
Elimination Half ◽  
Endogenous Compounds ◽  
Polymerase Chain ◽  
Anti Inflammatory ◽  
Glucuronosyl Transferase

Background: Mouse Udp-glucuronosyl Transferase (UGT) 2b1 is equivalent to the human UGT2B7 enzyme, which is a phase II drug-metabolising enzyme and plays a major role in the metabolism of xenobiotic and endogenous compounds. This study aimed to find the relative expression of the mouse ugt2b1 gene in the liver, kidney, and heart organs and the influence of Nonsteroidal Anti-inflammatory Drug (NSAID) administration. Methods: Thirty-five Blab/c mice were divided into 5 groups and treated with different commonly-used NSAIDs; diclofenac, ibuprofen, meloxicam, and mefenamic acid for 14 days. The livers, kidneys, and hearts were isolated, while the expression of ugt2b1 gene was analysed with a quantitative real-time polymerase chain reaction technique. Results: It was found that the ugt2b1 gene is highly expressed in the liver, and then in the heart and the kidneys. NSAIDs significantly upregulated (ANOVA, p < 0.05) the expression of ugt2b1 in the heart, while they downregulated its expression (ANOVA, p < 0.05) in the liver and kidneys. The level of NSAIDs’ effect on ugt2b1 gene expression was strongly correlated (Spearman’s Rho correlation, p < 0.05) with NSAID’s lipophilicity in the liver and its elimination half-life in the heart. Conclusion: This study concluded that the mouse ugt2b1 gene was mainly expressed in the liver, as 14-day administration of different NSAIDs caused alterations in the expression of this gene, which may influence the metabolism of xenobiotic and endogenous compounds.

scholarly journals The Integrated RNA Landscape of Renal Preconditioning against Ischemia-Reperfusion Injury

2020 ◽  
Vol 31 (4) ◽  
pp. 716-730 ◽  
Author(s):  
Marc Johnsen ◽  
Torsten Kubacki ◽  
Assa Yeroslaviz ◽  
Martin Richard Späth ◽  
Jannis Mörsdorf ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reperfusion Injury ◽  
Caloric Restriction ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Hypoxic Preconditioning ◽  
Preventive Strategies ◽  
Gene Expression Signatures

BackgroundAlthough AKI lacks effective therapeutic approaches, preventive strategies using preconditioning protocols, including caloric restriction and hypoxic preconditioning, have been shown to prevent injury in animal models. A better understanding of the molecular mechanisms that underlie the enhanced resistance to AKI conferred by such approaches is needed to facilitate clinical use. We hypothesized that these preconditioning strategies use similar pathways to augment cellular stress resistance.MethodsTo identify genes and pathways shared by caloric restriction and hypoxic preconditioning, we used RNA-sequencing transcriptome profiling to compare the transcriptional response with both modes of preconditioning in mice before and after renal ischemia-reperfusion injury.ResultsThe gene expression signatures induced by both preconditioning strategies involve distinct common genes and pathways that overlap significantly with the transcriptional changes observed after ischemia-reperfusion injury. These changes primarily affect oxidation-reduction processes and have a major effect on mitochondrial processes. We found that 16 of the genes differentially regulated by both modes of preconditioning were strongly correlated with clinical outcome; most of these genes had not previously been directly linked to AKI.ConclusionsThis comparative analysis of the gene expression signatures in preconditioning strategies shows overlapping patterns in caloric restriction and hypoxic preconditioning, pointing toward common molecular mechanisms. Our analysis identified a limited set of target genes not previously known to be associated with AKI; further study of their potential to provide the basis for novel preventive strategies is warranted. To allow for optimal interactive usability of the data by the kidney research community, we provide an online interface for user-defined interrogation of the gene expression datasets (http://shiny.cecad.uni-koeln.de:3838/IRaP/).

scholarly journals Modulation of the Immune Response by Deferasirox in Myelodysplastic Syndrome Patients

2021 ◽  
Vol 14 (1) ◽  
pp. 41
Author(s):  
Hana Votavova ◽  
Zuzana Urbanova ◽  
David Kundrat ◽  
Michaela Dostalova Merkerova ◽  
Martin Vostry ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Blood Cell ◽  
Myelodysplastic Syndrome ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Adaptive Immune Response ◽  
Gene Expression Profiles ◽  
Iron Chelator ◽  
Multiple Cancer

Deferasirox (DFX) is an oral iron chelator used to reduce iron overload (IO) caused by frequent blood cell transfusions in anemic myelodysplastic syndrome (MDS) patients. To study the molecular mechanisms by which DFX improves outcome in MDS, we analyzed the global gene expression in untreated MDS patients and those who were given DFX treatment. The gene expression profiles of bone marrow CD34+ cells were assessed by whole-genome microarrays. Initially, differentially expressed genes (DEGs) were determined between patients with normal ferritin levels and those with IO to address the effect of excessive iron on cellular pathways. These DEGs were annotated to Gene Ontology terms associated with cell cycle, apoptosis, adaptive immune response and protein folding and were enriched in cancer-related pathways. The deregulation of multiple cancer pathways in iron-overloaded patients suggests that IO is a cofactor favoring the progression of MDS. The DEGs between patients with IO and those treated with DFX were involved predominantly in biological processes related to the immune response and inflammation. These data indicate DFX modulates the immune response mainly via neutrophil-related genes. Suppression of negative regulators of blood cell differentiation essential for cell maturation and upregulation of heme metabolism observed in DFX-treated patients may contribute to the hematopoietic improvement.

scholarly journals Mapping chromatin accessibility and active regulatory elements reveals pathological mechanisms in human gliomas

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Karolina Stępniak ◽  
Magdalena A. Machnicka ◽  
Jakub Mieczkowski ◽  
Anna Macioszek ◽  
Bartosz Wojtaś ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chromatin Structure ◽  
Molecular Mechanisms ◽  
Genome Mapping ◽  
Malignant Gliomas ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Multiple Tumor ◽  
Genes Encoding ◽  
Methylation Patterns

AbstractChromatin structure and accessibility, and combinatorial binding of transcription factors to regulatory elements in genomic DNA control transcription. Genetic variations in genes encoding histones, epigenetics-related enzymes or modifiers affect chromatin structure/dynamics and result in alterations in gene expression contributing to cancer development or progression. Gliomas are brain tumors frequently associated with epigenetics-related gene deregulation. We perform whole-genome mapping of chromatin accessibility, histone modifications, DNA methylation patterns and transcriptome analysis simultaneously in multiple tumor samples to unravel epigenetic dysfunctions driving gliomagenesis. Based on the results of the integrative analysis of the acquired profiles, we create an atlas of active enhancers and promoters in benign and malignant gliomas. We explore these elements and intersect with Hi-C data to uncover molecular mechanisms instructing gene expression in gliomas.

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