Publications by authors named "Silvia Requena"

Introduction: CD8 cytotoxic T lymphocytes (CTLs) are highly effective in defending against viral infections and tumours. They are activated through the recognition of peptide-MHC-I complex by the T-cell receptor (TCR) and co-stimulation. This cognate interaction promotes the organisation of intimate cell-cell connections that involve cytoskeleton rearrangement to enable effector function and clearance of the target cell.

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  • The mitochondrial network's organization significantly impacts T cell metabolism and their response to T cell receptor (TCR) stimulation, requiring dynamic changes in the cytoskeleton.
  • Activation signals like TCR and CD28 lead to mitochondrial polarization and movement towards the immune synapse, crucial for T cell function.
  • The study emphasizes the role of End-binding protein 1 (EB1) in regulating cytoskeletal structure and mitochondrial arrangement, linking cytoskeleton dynamics to metabolic efficiency and functionality in activated CD4 T cells.
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T cell activation through TCR stimulation leads to the formation of the immunological synapse (IS), a specialized adhesion organized between T lymphocytes and antigen presenting cells (APCs) in which a dynamic interaction among signaling molecules, the cytoskeleton and intracellular organelles achieves proper antigen-mediated stimulation and effector function. The kinetics of molecular reactions at the IS is essential to determine the quality of the response to the antigen stimulation. Herein, we describe methods based on biochemistry, flow cytometry and imaging in live and fixed cells to study the activation state and dynamics of regulatory molecules at the IS in the Jurkat T cell line CH7C17 and primary human and mouse CD4 T lymphocytes stimulated by antigen presented by Raji and HOM2 B cell lines and human and mouse dendritic cells.

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Cell proteostasis includes gene transcription, protein translation, folding of de novo proteins, post-translational modifications, secretion, degradation and recycling. By profiling the proteome of extracellular vesicles (EVs) from T cells, we have found the chaperonin complex CCT, involved in the correct folding of particular proteins. By limiting CCT cell-content by siRNA, cells undergo altered lipid composition and metabolic rewiring towards a lipid-dependent metabolism, with increased activity of peroxisomes and mitochondria.

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  • * RNA sequencing on Jurkat T cells revealed that CD69-oxLDL interactions lead to the expression of anti-inflammatory NR4A receptors and PD-1, indicating their role in modulating immune responses.
  • * In human arteries with chronic inflammation, increased levels of PD-1, CD69, and NR4A3 were observed, suggesting that CD69 may help regulate inflammation and vascular remodeling independently of traditional T cell receptor signaling.
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  • COVID-19 pneumonia is a severe infectious disease that poses a significant risk, particularly to older patients with existing health issues, and the mechanisms behind it are still not fully understood.
  • The study compared the profiles of specific miRNAs and cytokines in patients with COVID-19 and those with other forms of pneumonia, leading to the identification of 15 miRNAs that are altered in COVID-19.
  • A subgroup of four specific miRNAs was found to effectively distinguish between COVID-19 and other pneumonia cases, while certain cytokine levels also differed significantly between mild and severe COVID-19 patients, contributing to a better understanding of the disease's underlying mechanisms.
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Tubulin post-translational modifications (PTMs) constitute a source of diversity for microtubule (MT) functions, in addition to the different isotypes of α and β-tubulin acting as building blocks of MTs. Also, MT-associated proteins (MAPs) confer different characteristics to MTs. The combination of all these factors regulates the stability of these structures that act as rails to transport organelles within the cell, facilitating the association of motor complexes.

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Background: Whereas HIV-1 has spread globally, HIV-2 is mainly found in West Africa where dual HIV-1/HIV-2 coinfection is nowadays uncommon. Herein, we report the rate, main characteristics, and treatment outcomes of all dually infected patients living in Spain.

Methods: We identified retrospectively all persons coinfected with HIV-1 recorded at the Spanish HIV-2 registry.

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Chronic hepatitis C virus (HCV) infection is one of the major causes of death worldwide due to infectious agents. The advent of direct-acting antivirals has dramatically improved the chance of HCV elimination, even for patients with decompensated cirrhosis. Along with HCV cure, benefits are recognized in terms of regression of liver fibrosis and risk of hepatocellular carcinoma.

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Background: Treatment with direct-acting antivirals (DAA) eradicates hepatitis C virus (HCV) from most chronic carriers. Information on regression of liver fibrosis and the influence of HIV is scarce in cured patients.

Methods: All consecutive HCV-infected individuals treated with DAA at our institution were examined.

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Current antiretroviral therapy allows to achieve and sustain maximal suppression of HIV replication in most treated patients. As result, the life expectancy of HIV-infected persons has improved dramatically and is nowadays similar to that of the HIV-negative population. However, oral antiretrovirals have to be taken daily and indefinitely to avoid resumption of HIV replication and selection of drug resistance.

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Oral DAA have demonstrated high efficacy as treatment of hepatitis C. However, the presence of resistance-associated substitutions (RAS) at baseline has occasionally been associated with impaired treatment response. Herein, we examined the impact of baseline RAS at the HCV NS5A gene region on treatment response in a real-life setting.

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  • HTLV-1 is a neglected viral infection affecting around 15 million people worldwide, with less than 10% developing serious conditions like tropical spastic paraparesis (TSP) and adult T-cell leukemia (ATL).
  • The virus spreads mainly through breastfeeding, sexual contact, and transfusions, but there are no vaccines or effective antiviral treatments available.
  • In Spain, there have been 327 reported cases, mostly among Latin American immigrants, and a significant underdiagnosis suggests the need for improved screening, especially for organ transplant donors and pregnant women.
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Background: A broader extent of amino acid substitutions in the integrase of HIV-2 compared with HIV-1 might enable greater cross-resistance between raltegravir and dolutegravir in HIV-2 infection. Few studies have examined the virological response to dolutegravir in HIV-2 patients that failed raltegravir.

Methods: All patients recorded in the HIV-2 Spanish cohort were examined.

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: HIV type 2 (HIV-2) is a neglected virus despite estimates of 1-2 million people infected worldwide. HIV-2 is less efficiently transmitted than HIV-1 by sex and from mother to child. Although AIDS may develop in HIV-2 carriers, it takes longer than in HIV-1-infected patients.

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Since hepatitis C virus (HCV) and human T-lymphotropic virus (HTLV) share transmission routes, dual infection could be frequent. In Spain, HTLV underdiagnosis is highlighted by the high proportion of patients presenting either with tropical spastic paraparesis (TSP) or adult T-cell leukemia (ATL) at first diagnosis. We examined whether the renewed efforts for expanding HCV testing may provide a sentinel population that might selectively be targeted to unveil asymptomatic HTLV carriers.

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Background: Single nucleotide polymorphisms (SNPs) at the ITPA gene are associated with haemolytic anaemia in chronic hepatitis C patients treated with pegylated interferon-ribavirin (RBV). Information in patients treated with interferon-free, direct-acting antivirals (DAA) is scarce.

Methods: Median haemoglobin (Hb) levels were compared at baseline and at week 4, when ribavirin concentration achieves steady state, in all consecutive chronic hepatitis C patients treated with oral DAA plus RBV at our clinic.

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