The Role of Glycosyltransferases in Colorectal Cancer Fernández-Ponce, Cecilia; Geribaldi-Doldán, Noelia; Sánchez-Gomar, Ismael ...
International journal of molecular sciences,
05/2021, Letnik:
22, Številka:
11
Journal Article
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Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Post-translational modifications (PTMs) have been extensively studied in malignancies due to its relevance in tumor ...pathogenesis and therapy. This review is focused on the dysregulation of glycosyltransferase expression in CRC and its impact in cell function and in several biological pathways associated with CRC pathogenesis, prognosis and therapeutic approaches. Glycan structures act as interface molecules between cells and their environment and in several cases facilitate molecule function. CRC tissue shows alterations in glycan structures decorating molecules, such as annexin-1, mucins, heat shock protein 90 (Hsp90), β1 integrin, carcinoembryonic antigen (CEA), epidermal growth factor receptor (EGFR), insulin-like growth factor-binding protein 3 (IGFBP3), transforming growth factor beta (TGF-β) receptors, Fas (CD95), PD-L1, decorin, sorbin and SH3 domain-containing protein 1 (SORBS1), CD147 and glycosphingolipids. All of these are described as key molecules in oncogenesis and metastasis. Therefore, glycosylation in CRC can affect cell migration, cell–cell adhesion, actin polymerization, mitosis, cell membrane repair, apoptosis, cell differentiation, stemness regulation, intestinal mucosal barrier integrity, immune system regulation, T cell polarization and gut microbiota composition; all such functions are associated with the prognosis and evolution of the disease. According to these findings, multiple strategies have been evaluated to alter oligosaccharide processing and to modify glycoconjugate structures in order to control CRC progression and prevent metastasis. Additionally, immunotherapy approaches have contemplated the use of neo-antigens, generated by altered glycosylation, as targets for tumor-specific T cells or engineered CAR (Chimeric antigen receptors) T cells.
The complex physiology of eukaryotic cells is regulated through numerous mechanisms, including epigenetic changes and posttranslational modifications. The wide-ranging diversity of these mechanisms ...constitutes a way of dynamic regulation of the functionality of proteins, their activity, and their subcellular localization as well as modulation of the differential expression of genes in response to external and internal stimuli that allow an organism to respond or adapt to accordingly. However, alterations in these mechanisms have been evidenced in several autoimmune diseases, including systemic lupus erythematosus (SLE). The present review aims to provide an approach to the current knowledge of the implications of these mechanisms in SLE pathophysiology.
The defining characteristic of neural stem cells (NSCs) is their ability to multiply through symmetric divisions and proliferation, and differentiation by asymmetric divisions, thus giving rise to ...different types of cells of the central nervous system (CNS). A strict temporal space control of the NSC differentiation is necessary, because its alterations are associated with neurological dysfunctions and, in some cases, death. This work reviews the current state of the molecular mechanisms that regulate the transcription in NSCs, organized according to whether the origin of the stimulus that triggers the molecular cascade in the CNS is internal (intrinsic factors) or whether it is the result of the microenvironment that surrounds the CNS (extrinsic factors).
The Role of Microglia in Glioblastoma Geribaldi-Doldán, Noelia; Fernández-Ponce, Cecilia; Quiroz, Roberto Navarro ...
Frontiers in oncology,
01/2021, Letnik:
10
Journal Article
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Glioblastoma (GB), the most aggressive malignant glioma, is made up of a large percentage of glioma-associated microglia/macrophages (GAM), suggesting that immune cells play an important role in the ...pathophysiology of GB. Under physiological conditions, microglia, the phagocytes of the central nervous system (CNS), are involved in various processes such as neurogenesis or axonal growth, and the progression of different conditions such as Alzheimer's disease. Through immunohistochemical studies, markers that enhance GB invasiveness have been shown to be expressed in the peritumoral area of the brain, such as Transforming Growth Factor α (TGF-α), Stromal Sell-Derived Factor 1 (SDF1/CXCL12), Sphingosine-1-Phosphate (S1P) and Neurotrophic Factor Derived from the Glial cell line (GDNF), contributing to the increase in tumor mass. Similarly, it has also been described 17 biomarkers that are present in hypoxic periarteriolar HSC niches in bone marrow and in hypoxic periarteriolar GSC niches in glioblastoma. Interestingly, microglia plays an important role in the microenvironment that supports GB progression, being one of the most important focal points in the study of therapeutic targets for the development of new drugs. In this review, we describe the altered signaling pathways in microglia in the context of GB. We also show how microglia interact with glioblastoma cells and the epigenetic mechanisms involved. Regarding the interactions between microglia and neurogenic niches, some authors indicate that glioblastoma stem cells (GSC) are similar to neural stem cells (NSC), common stem cells in the subventricular zone (SVZ), suggesting that this could be the origin of GB. Understanding the similarities between SVZ and the tumor microenvironment could be important to clarify some mechanisms involved in GB malignancy and to support the discovering of new therapeutic targets for the development of more effective glioblastoma treatments.
Arterial hypertension (AH) is a multifactorial and asymptomatic disease that affects vital organs such as the kidneys and heart. Considering its prevalence and the associated severe health ...repercussions, hypertension has become a disease of great relevance for public health across the globe. Conventionally, the classification of an individual as hypertensive or non-hypertensive is conducted through ambulatory blood pressure monitoring over a 24-h period. Although this method provides a reliable diagnosis, it has notable limitations, such as additional costs, intolerance experienced by some patients, and interferences derived from physical activities. Moreover, some patients with significant renal impairment may not present proteinuria. Accordingly, alternative methodologies are applied for the classification of individuals as hypertensive or non-hypertensive, such as the detection of metabolites in urine samples through liquid chromatography or mass spectrometry. However, the high cost of these techniques limits their applicability for clinical use. Consequently, an alternative methodology was developed for the detection of molecular patterns in urine collected from hypertension patients. This study generated a direct discrimination model for hypertensive and non-hypertensive individuals through the amplification of Raman signals in urine samples based on gold nanoparticles and supported by chemometric techniques such as partial least squares-discriminant analysis (PLS-DA). Specifically, 162 patient urine samples were used to create a PLS-DA model. These samples included 87 urine samples from patients diagnosed with hypertension and 75 samples from non-hypertensive volunteers. In the AH group, 35 patients were diagnosed with kidney damage and were further classified into a subgroup termed (RAH). The PLS-DA model with 4 latent variables (LV) was used to classify the hypertensive patients with external validation prediction (P) sensitivity of 86.4%, P specificity of 77.8%, and P accuracy of 82.5%. This study demonstrates the ability of surface-enhanced Raman spectroscopy to differentiate between hypertensive and non-hypertensive patients through urine samples, representing a significant advance in the detection and management of AH. Additionally, the same model was then used to discriminate only patients diagnosed with renal damage and controls with a P sensitivity of 100%, P specificity of 77.8%, and P accuracy of 82.5%.
The aim of this study was to identity in silico the relationships among microRNAs (miRNAs) and genes encoding transcription factors, ubiquitylation, DNA methylation, and histone modifications in ...systemic lupus erythematosus (SLE). To identify miRNA dysregulation in SLE, we used miR2Disease and PhenomiR for information about miRNAs exhibiting differential regulation in disease and other biological processes, and HMDD for information about experimentally supported human miRNA-disease association data from genetics, epigenetics, circulating miRNAs, and miRNA-target interactions. This information was incorporated into the miRNA analysis. High-throughput sequencing revealed circulating miRNAs associated with kidney damage in patients with SLE. As the main finding of our in silico analysis of miRNAs differentially expressed in SLE and their interactions with disease-susceptibility genes, post-translational modifications, and transcription factors; we highlight 226 miRNAs associated with genes and processes. Moreover, we highlight that alterations of miRNAs such as hsa-miR-30a-5p, hsa-miR-16-5p, hsa-miR-142-5p, and hsa-miR-324-3p are most commonly associated with post-translational modifications. In addition, altered miRNAs that are most frequently associated with susceptibility-related genes are hsa-miR-16-5p, hsa-miR-374a-5p, hsa-miR-34a-5p, hsa-miR-31-5p, and hsa-miR-1-3p.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this review, we were interested to identify the wide universe of enzymes associated with epigenetic modifications, whose gene expression is regulated by miRNAs with a high relative abundance in ...Crohn's disease (CD) affected tissues, with the aim to determine their impact in the pathogenesis and evolution of the disease.
We used HMDD and Bibliometrix R-package in order to identify the miRNAs overexpressed in CD. The identified enzymes associated with epigenetic mechanisms and post-translational modifications, regulated by miRNAs upregulated in CD, were analyzed using String v11 database.
We found 190 miRNAs with great abundance in patients with CD, of which 26 miRNAs regulate the gene expression of enzymes known to catalyze epigenetic modifications involved in essentials pathophysiological processes, such as chromatin architecture reorganization, immune response regulation including CD4+ T cells polarization, integrity of gut mucosa, gut microbiota composition and tumorigenesis.
The integrated analysis of miRNAs with a high relative abundance in patients with CD showed a combined and superimposed gene expression regulation of enzymes associated with relevant epigenetic mechanisms and that could explain, in part, the pathogenesis of CD.
Compromiso renal y digestivo en infecciones por COVID-19 Navarro-Quiroz, Roberto C; Atencio-Ibarra, Linda; Herrera Usuga, Juan Carlos ...
Revista colombiana de nefrología (En línea),
12/2020, Letnik:
7, Številka:
suppl 2
Journal Article
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La infección por el síndrome respiratorio agudo severo (SARS-CoV-2) ha causado una de las emergencias epidemiológicas más grandes de los últimos 10 años y sus efectos patológicos son aún estudiados. ...Por lo anterio, resulta importante describir los mecanismos asociados al compromiso renal y digestivo en la infección por SARS-CoV-2. Los mecanismos patológicos en tejido renal y en intestino causados por la infección por SARS-CoV-2 son propios del tropismo viral por células de estos sistemas y de los mecanismos citopáticos de etapa lítica de la infección, con una liberación continua de viriones que favorece la generación de un entorno inflamatorio con la consecuente secreción descontrolada de citoquinas proinflamatorias que conducen a la infección entérica del intestino y a las alteraciones en el riñón.
La educación en ciencias biológicas juega un papel importante a la hora de entender los sistemas vivos y ecosistemas que nos rodea en contexto de una epidemia de tipo zoonótico como SARS-CoV-2 y ...cumple un papel importante para el autocuidado en pacientes con enfermedad renal que son una población en alto riesgo según datos epidemiológicos. El presente trabajo pretende describir la asociación entre la educación en ciencia biológica y la epidemia por COVID-19. La educación en ciencias biológicas es un componente importante supeditado al autocuidado para que muchos pacientes con enfermedad renal puedan entender la importancia de tener una mejor adherencia al régimen terapéutico y el régimen alimenticio, y en el caso puntual de la epidemia por COVID-19 puede permitir que ellostomen las medidas preventivas que eviten su exposición al patógeno.
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