65 research outputs found

    Applications of Polyanionic Carbosilane Dendrimers against HIV-1 and HCMV

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    Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de Lectura: 24-01-2022Viral outbreaks are one of the main foci nowadays due to the actual Sars-Cov2 pandemic. Therefore, new therapies and treatments are needed to fight, not only the new viral challenges, but also viruses that in several countries have caused a non-stop pandemic since several years ago, as Human Immunodeficiency Virus (VIH) or Human Cytomegalovirus (HCMV). The high cost of present treatments and the lack of routinely tests in these countries urge the necessity to develop new molecules or strategies against these viruses. Foremost, in immunosuppressed individuals, as HIV patients, HCMV infection can lead to dissemination and life-threatening end-organ diseases. The new treatments should be low-cost and capable of avoiding the emerging problem of resistant virus. Nanotechnology is rising as a promising alternative in response to the need of efficient, immediate and cost-effective therapies. Dendrimers are a group of nanoparticles that have shown promising results against viral infectious diseases. In this work we demonstrated three different applications of Polyanionic Carbosilane Dendrimers. First, we showed the reactivation activity of G3-S16 in a monocytic derived cell line, and the promising results in the combination with the actual Latency Reversal Agents for the “Shock and Kill” approach. Second, we evaluated the ability of G2-S16 dendrimer to inhibit HIV cell to cell transmission in Monocyte Derived Macrophages (MDMs). We co cultured, treated, and infected MDMs with healthy T lymphocytes to measure cell to cell transmission, our results showed that G2-S16 is capable of inhibit HIV infectivity inside MDMs, thus reducing or eliminating reservoir or sanctuaries formation. Third, we demonstrated the potent inhibition activity of G2-S16 and G2-S24P against HCMV infection in human lung fibroblast. We studied the mechanism of action of these dendrimers, showing that in contrast with other viruses, G2-S16 and G2-S24P do not inhibit HCMV attachment in MRC-5. Moreover, we evaluated the combination of both dendrimers with the actual treatment, ganciclovir, the results showed an increased potency and time effect against HCMV infectionThis thesis is based upon work from COST Action CA 17140 “Cancer Nanomedicine from the Bench to the Bedside” supported by COST (European Cooperation in Science and Technology). The Spanish HIV BioBank is supported by Instituto de Salud Carlos III, Spanish Healt Ministry (Grant nº RD06/0006/0035, RD12/0017/0037 and RD16/0025/0019) as part of the Plan Nacional R + D + I and cofinanced by ISCIII- Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER)”. The RIS Cohort (CoRIS) is funded by the Instituto de Salud Carlos III through the Red Temática de Investigación Cooperativa en SIDA (RIS C03/173, RD12/0017/0018 and RD16/0002/0006) as part of the Plan Nacional R + D + I and cofinanced by ISCIII-Subdirección General de Evaluacion y el Fondo Europeo de Desarrollo Regional (FEDER) 2018-202

    Медицински речник

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    Второ издание - дополнето и изменето Етимолошки, латински, англиски, македонски речник Македонско-латински речник Англиско-македонски - латински речник Епонимен речник Посебни додатоци Библиографиј

    Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)

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    The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer-reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state-of-the-art handbook for basic and clinical researchers

    Modern Tools for Genetic Engineering

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    Site-specific endonucleases create double-strand breaks within the genome and can be targeted to literally any genetic mutation. Together with a repair template, a correction of the defective locus becomes possible. This book offers insight into the modern tools of genome editing, their hurdles and their huge potential. A new era of in vivo genetic engineering has begun

    Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)

    Get PDF
    The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer‐reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state‐of‐the‐art handbook for basic and clinical researchers.DFG, 389687267, Kompartimentalisierung, Aufrechterhaltung und Reaktivierung humaner Gedächtnis-T-Lymphozyten aus Knochenmark und peripherem BlutDFG, 80750187, SFB 841: Leberentzündungen: Infektion, Immunregulation und KonsequenzenEC/H2020/800924/EU/International Cancer Research Fellowships - 2/iCARE-2DFG, 252623821, Die Rolle von follikulären T-Helferzellen in T-Helferzell-Differenzierung, Funktion und PlastizitätDFG, 390873048, EXC 2151: ImmunoSensation2 - the immune sensory syste

    Current Perspectives in HIV Infection

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    This book gives a comprehensive overview of HIV and AIDS including NeuroAIDS, as well as general concepts of pathology, immunity and immunopathology, diagnosis, treatment, epidemiology and etiology to current clinical recommendations in management of HIV/AIDS including NeuroAIDS, highlighting the ongoing issues, recent advances and future directions in diagnostic approaches and therapeutic strategies

    Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)

    Get PDF
    The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer-reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state-of-the-art handbook for basic and clinical researchers

    Pharmacological treatments of COVID-19

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    The viral infection due to the new coronavirus or coronavirus disease 2019 (COVID-19), which was reported for the first time in December 2019, was named by the World Health Organization (WHO) as Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV2), because of the very similar genome and also its related symptoms to SARS-CoV1. The ongoing COVID-19 pandemic with significant mortality, morbidity, and socioeconomic impact is considered by the WHO as a global public health emergency. Since there is no specific treatment available for SARS-CoV2 infection, and or COVID-19, several clinical and sub-clinical studies are currently undertaken to find a gold-standard therapeutic regimen with high efficacy and low side effect. Based on the published scientific evidence published to date, we summarized herein the effects of different potential therapies and up-to-date clinical trials. The review is intended to help readers aware of potentially effective COVID-19 treatment and provide useful references for future studies. © 2020, Maj Institute of Pharmacology Polish Academy of Sciences

    Characterization of the E4 protein of human papillomaviruses as an enhancer of HIV infection

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    Cross-regulation of viral kinases with cyclin A secures shutoff of host DNA synthesis

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    Herpesviruses encode conserved protein kinases (CHPKs) to stimulate phosphorylation-sensitive processes during infection. How CHPKs bind to cellular factors and how this impacts their regulatory functions is poorly understood. Here, we use quantitative proteomics to determine cellular interaction partners of human herpesvirus (HHV) CHPKs. We find that CHPKs can target key regulators of transcription and replication. The interaction with Cyclin A and associated factors is identified as a signature of β-herpesvirus kinases. Cyclin A is recruited via RXL motifs that overlap with nuclear localization signals (NLS) in the non-catalytic N termini. This architecture is conserved in HHV6, HHV7 and rodent cytomegaloviruses. Cyclin A binding competes with NLS function, enabling dynamic changes in CHPK localization and substrate phosphorylation. The cytomegalovirus kinase M97 sequesters Cyclin A in the cytosol, which is essential for viral inhibition of cellular replication. Our data highlight a fine-tuned and physiologically important interplay between a cellular cyclin and viral kinases
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