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  1. Article ; Online: Patient perspectives of the influence of severe and non-severe asthma on their quality of life: A national survey of asthma patients in Spain.

    Chiner, Eusebi / Hernández, Carme / Blanco-Aparicio, Marina / Funenga-Fitas, Eunice / Jiménez-Ruiz, Carlos

    The clinical respiratory journal

    2021  Volume 16, Issue 2, Page(s) 130–141

    Abstract: Introduction: Little is known about adult asthma patients' perspective of their disease burden. This study aimed to obtain a comprehensive picture of patient needs, evaluate their knowledge, source of information, and perception of the severity of their ...

    Abstract Introduction: Little is known about adult asthma patients' perspective of their disease burden. This study aimed to obtain a comprehensive picture of patient needs, evaluate their knowledge, source of information, and perception of the severity of their asthma, and compare these variables between severe (SA) and non-severe (NSA) asthma patients.
    Methods: We conducted an online cross-sectional survey in Spain among asthma patients aged ≥18 years. A bespoke questionnaire was used to collect sociodemographic data, asthma characteristics, treatments, disease burden, patient's perception of disease severity, and asthma information sources. Patients were classified as SA and NSA according to GINA 2020 treatment steps recommendations. To compare populations, 600 participants (200 SA and 400 NSA) were randomly selected to complete the survey.
    Results: Participants were mostly women, mean age >38 years. SA patients underestimated the severity of their asthma; 52% judged it as mild, and only 2% considered their asthma severe. Overall, 50% of NSA and 96% of SA patients had experienced ≥1 exacerbation the previous year (p < 0.001). Fewer asthma exacerbations (SA) and improved quality of life (QoL) (NSA) were the most frequently expected therapy outcomes. NSA patients believe that asthma impacts their daily life (37%) and worsens QoL (34%) to a lesser degree than SA (67% and 59%, respectively; p < 0.001). Patient-preferred sources of information were specialists (NSA:42%; SA: 38%) and primary care physicians (NSA: 41%; SA: 33%).
    Conclusions: Despite the effective therapies currently available, the results of this study still show a significant emotional burden and QoL impairment in patients with severe asthma.
    MeSH term(s) Adolescent ; Adult ; Asthma/epidemiology ; Asthma/therapy ; Cost of Illness ; Cross-Sectional Studies ; Female ; Humans ; Quality of Life ; Spain/epidemiology
    Language English
    Publishing date 2021-11-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 2442214-9
    ISSN 1752-699X ; 1752-6981
    ISSN (online) 1752-699X
    ISSN 1752-6981
    DOI 10.1111/crj.13461
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: OGG1 Inhibition Triggers Synthetic Lethality and Enhances The Effect of PARP Inhibitor Olaparib in BRCA1-Deficient TNBC Cells.

    Baquero, Juan Miguel / Marchena-Perea, Erik / Mirabet, Rocío / Torres-Ruiz, Raúl / Blanco-Aparicio, Carmen / Rodríguez-Perales, Sandra / Helleday, Thomas / Benítez-Buelga, Carlos / Benítez, Javier / Osorio, Ana

    Frontiers in oncology

    2022  Volume 12, Page(s) 888810

    Abstract: Background: PARP1 plays a critical role in the base excision repair (BER) pathway, and PARP1 inhibition leads to specific cell death, through a synthetic lethal interaction, in the context of : Methods: We hypothesized that other BER members could be ...

    Abstract Background: PARP1 plays a critical role in the base excision repair (BER) pathway, and PARP1 inhibition leads to specific cell death, through a synthetic lethal interaction, in the context of
    Methods: We hypothesized that other BER members could be additional synthetic lethal partners with mutated BRCA genes. To test this, we decided to evaluate the glycosylase OGG1 as a potential candidate, by treating BRCA1 proficient and deficient breast cancer cells with PARPi olaparib and the OGG1 inhibitor TH5478.
    Results: Knocking out
    Discussion: These results provide the first evidence that OGG1 inhibition is a promising new synthetic lethality strategy in
    Language English
    Publishing date 2022-05-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2022.888810
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Pim kinases in cancer: diagnostic, prognostic and treatment opportunities.

    Blanco-Aparicio, Carmen / Carnero, Amancio

    Biochemical pharmacology

    2012  Volume 85, Issue 5, Page(s) 629–643

    Abstract: PIM proteins belong to a family of ser/thr kinases composed of 3 members, PIM1, PIM2 and PIM3, with greatly overlapping functions. PIM kinases are mainly responsible for cell cycle regulation, antiapoptotic activity and the homing and migration of ... ...

    Abstract PIM proteins belong to a family of ser/thr kinases composed of 3 members, PIM1, PIM2 and PIM3, with greatly overlapping functions. PIM kinases are mainly responsible for cell cycle regulation, antiapoptotic activity and the homing and migration of receptor tyrosine kinases mediated via the JAK/STAT pathway. PIM kinases have been found to be upregulated in many hematological malignancies and solid tumors. Although these kinases have been described as weak oncogenes, they are heavily targeted for anticancer drug discovery. The present review summarizes the discoveries made to date regarding PIM kinases as driving oncogenes in the process of tumorigenesis and their validation as drug targets.
    MeSH term(s) Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Drug Discovery ; Gene Expression Regulation, Enzymologic/physiology ; Gene Expression Regulation, Neoplastic/physiology ; Humans ; Proto-Oncogene Proteins c-pim-1/antagonists & inhibitors ; Proto-Oncogene Proteins c-pim-1/genetics ; Proto-Oncogene Proteins c-pim-1/metabolism
    Chemical Substances Antineoplastic Agents ; Proto-Oncogene Proteins c-pim-1 (EC 2.7.11.1) ; proto-oncogene proteins pim (EC 2.7.11.1)
    Language English
    Publishing date 2012-10-05
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 208787-x
    ISSN 1873-2968 ; 0006-2952
    ISSN (online) 1873-2968
    ISSN 0006-2952
    DOI 10.1016/j.bcp.2012.09.018
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: mTORC2 Is the Major Second Layer Kinase Negatively Regulating FOXO3 Activity.

    Jimenez, Lucia / Amenabar, Carlos / Mayoral-Varo, Victor / Mackenzie, Thomas A / Ramos, Maria C / Silva, Andreia / Calissi, Giampaolo / Grenho, Inês / Blanco-Aparicio, Carmen / Pastor, Joaquin / Megías, Diego / Ferreira, Bibiana I / Link, Wolfgang

    Molecules (Basel, Switzerland)

    2022  Volume 27, Issue 17

    Abstract: Forkhead box O (FOXO) proteins are transcription factors involved in cancer and aging and their pharmacological manipulation could be beneficial for the treatment of cancer and healthy aging. FOXO proteins are mainly regulated by post-translational ... ...

    Abstract Forkhead box O (FOXO) proteins are transcription factors involved in cancer and aging and their pharmacological manipulation could be beneficial for the treatment of cancer and healthy aging. FOXO proteins are mainly regulated by post-translational modifications including phosphorylation, acetylation and ubiquitination. As these modifications are reversible, activation and inactivation of FOXO factors is attainable through pharmacological treatment. One major regulatory input of FOXO signaling is mediated by protein kinases. Here, we use specific inhibitors against different kinases including PI3K, mTOR, MEK and ALK, and other receptor tyrosine kinases (RTKs) to determine their effect on FOXO3 activity. While we show that inhibition of PI3K efficiently drives FOXO3 into the cell nucleus, the dual PI3K/mTOR inhibitors dactolisib and PI-103 induce nuclear FOXO translocation more potently than the PI3Kδ inhibitor idelalisib. Furthermore, specific inhibition of mTOR kinase activity affecting both mTORC1 and mTORC2 potently induced nuclear translocation of FOXO3, while rapamycin, which specifically inhibits the mTORC1, failed to affect FOXO3. Interestingly, inhibition of the MAPK pathway had no effect on the localization of FOXO3 and upstream RTK inhibition only weakly induced nuclear FOXO3. We also measured the effect of the test compounds on the phosphorylation status of AKT, FOXO3 and ERK, on FOXO-dependent transcriptional activity and on the subcellular localization of other FOXO isoforms. We conclude that mTORC2 is the most important second layer kinase negatively regulating FOXO activity.
    MeSH term(s) Forkhead Box Protein O3/genetics ; Forkhead Box Protein O3/metabolism ; Forkhead Transcription Factors/genetics ; Forkhead Transcription Factors/metabolism ; Mechanistic Target of Rapamycin Complex 1 ; Mechanistic Target of Rapamycin Complex 2 ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; TOR Serine-Threonine Kinases
    Chemical Substances Forkhead Box Protein O3 ; Forkhead Transcription Factors ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; Mechanistic Target of Rapamycin Complex 2 (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; TOR Serine-Threonine Kinases (EC 2.7.11.1)
    Language English
    Publishing date 2022-08-24
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules27175414
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The PIM family of serine/threonine kinases in cancer.

    Narlik-Grassow, Maja / Blanco-Aparicio, Carmen / Carnero, Amancio

    Medicinal research reviews

    2014  Volume 34, Issue 1, Page(s) 136–159

    Abstract: The proviral insertion site in Moloney murine leukemia virus, or PIM proteins, are a family of serine/threonine kinases composed of three different isoforms (PIM1, PIM2, and PIM3) that are highly evolutionarily conserved. These proteins are regulated ... ...

    Abstract The proviral insertion site in Moloney murine leukemia virus, or PIM proteins, are a family of serine/threonine kinases composed of three different isoforms (PIM1, PIM2, and PIM3) that are highly evolutionarily conserved. These proteins are regulated primarily by transcription and stability through pathways that are controlled by Janus kinase/Signal transducer and activator of transcription, JAK/STAT, transcription factors. The PIM family proteins have been found to be overexpressed in hematological malignancies and solid tumors, and their roles in these tumors were confirmed in mouse tumor models. Furthermore, the PIM family proteins have been implicated in the regulation of apoptosis, metabolism, cell cycle, and homing and migration, which has led to the postulation of these proteins as interesting targets for anticancer drug discovery. In the present work, we review the importance of PIM kinases in tumor growth and as drug targets.
    MeSH term(s) Amino Acid Sequence ; Carcinogenesis/genetics ; Humans ; Molecular Sequence Data ; Neoplasms/enzymology ; Protein-Serine-Threonine Kinases/chemistry ; Protein-Serine-Threonine Kinases/metabolism ; Sequence Homology, Amino Acid ; Substrate Specificity
    Chemical Substances Protein-Serine-Threonine Kinases (EC 2.7.11.1)
    Language English
    Publishing date 2014-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 603210-2
    ISSN 1098-1128 ; 0198-6325
    ISSN (online) 1098-1128
    ISSN 0198-6325
    DOI 10.1002/med.21284
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  6. Article ; Online: Cyclosporin A-loaded dissolving microneedles for dermatitis therapy: Development, characterisation and efficacy in a delayed-type hypersensitivity in vivo model.

    Martínez-Navarrete, Miquel / Guillot, Antonio José / Lobita, Maria C / Recio, María Carmen / Giner, Rosa / Aparicio-Blanco, Juan / Montesinos, María Carmen / Santos, Hélder A / Melero, Ana

    Drug delivery and translational research

    2024  

    Abstract: Several drugs can be used for treating inflammatory skin pathologies like dermatitis and psoriasis. However, for the management of chronic and long-term cases, topical administration is preferred over oral delivery since it prevents certain issues due to ...

    Abstract Several drugs can be used for treating inflammatory skin pathologies like dermatitis and psoriasis. However, for the management of chronic and long-term cases, topical administration is preferred over oral delivery since it prevents certain issues due to systemic side effects from occurring. Cyclosporin A (CsA) has been used for this purpose; however, its high molecular weight (1202 Da) restricts the diffusion through the skin structure. Here, we developed a nano-in-micro device combining lipid vesicles (LVs) and dissolving microneedle array patches (DMAPs) for targeted skin delivery. CsA-LVs allowed the effective incorporation of CsA in the hydrophilic DMAP matrix despite the hydrophobicity of the drug. Polymeric matrix composed of poly (vinyl alcohol) (5% w/v), poly (vinyl pyrrolidine) (15% w/v) and CsA-LV dispersion (10% v/v) led to the formation of CsA-LVs@DMAPs with adequate mechanical properties to penetrate the stratum corneum barrier. The safety and biocompatibility were ensured in an in vitro viability test using HaCaT keratinocytes and L929 fibroblast cell lines. Ex vivo permeability studies in a Franz-diffusion cell setup showed effective drug retention in the skin structure. Finally, CsA-LVs@DMAPs were challenged in an in vivo murine model of delayed-type hypersensitivity to corroborate their potential to ameliorate skin inflammatory conditions. Different findings like photon emission reduction in bioluminescence study, normalisation of histological damage and decrease of inflammatory cytokines point out the effectivity of CsA-LVs@DMAPs to treat these conditions. Overall, our study demonstrates that CsA-LVs@DMAPs can downregulate the skin inflammatory environment which paves the way for their clinical translation and their use as an alternative to corticosteroid-based therapies.
    Language English
    Publishing date 2024-03-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2590155-2
    ISSN 2190-3948 ; 2190-393X
    ISSN (online) 2190-3948
    ISSN 2190-393X
    DOI 10.1007/s13346-024-01542-9
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  7. Article ; Online: Corrigendum to <' Omipalisib inspired macrocycles as dual PI3K/mTOR inhibitors' [Eur. J. Med. Chem. 211 (2021), 113109].

    Alvarez, Rosa M / García, Ana Belén / Riesco-Fagundo, Concepción / Martín, José I / Varela, Carmen / Rodríguez Hergueta, Antonio / González Cantalapiedra, Esther / Oyarzabal, Julen / Di Geronimo, Bruno / Lorenzo, Milagros / Albarrán, M Isabel / Cebriá, Antonio / Cebrián, David / Martínez-González, Sonia / Blanco-Aparicio, Carmen / Pastor, Joaquín

    European journal of medicinal chemistry

    2021  Volume 224, Page(s) 113703

    Language English
    Publishing date 2021-07-17
    Publishing country France
    Document type Published Erratum
    ZDB-ID 188597-2
    ISSN 1768-3254 ; 0009-4374 ; 0223-5234
    ISSN (online) 1768-3254
    ISSN 0009-4374 ; 0223-5234
    DOI 10.1016/j.ejmech.2021.113703
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Documento de consenso de enfermería en asma 2020.

    Vaquero-Lozano, Paz / Lassaletta-Goñi, Inmaculada / Giner-Donaire, Jordi / Gómez-Neira, María Del Carmen / Serra-Batlles, Joan / García-García, Rocío / Álvarez-Gutiérrez, Francisco Javier / Blanco-Aparicio, Marina / Díaz-Pérez, David

    Open respiratory archives

    2021  Volume 3, Issue 1, Page(s) 100079

    Abstract: Asthma is a chronic respiratory disease which presents with a risk of exacerbations. Good patient management and continuous monitoring are crucial for good disease control, and pharmacological and non-pharmacological interventions are essential for ... ...

    Title translation Asthma 2020 Nursing Consensus Document.
    Abstract Asthma is a chronic respiratory disease which presents with a risk of exacerbations. Good patient management and continuous monitoring are crucial for good disease control, and pharmacological and non-pharmacological interventions are essential for proper treatment. Nurses specialised in asthma can contribute to the correct management of asthmatic patients. They play a key role in diagnostic tests, administration of medication, and patient follow-up and education. This consensus arose from the need to address an aspect of asthma management that does not appear in the specific recommendations of current guidelines. This document highlights and updates the role of specialized nurses in the care and management of asthma patients, offering conclusions and practical recommendations with the aim of improving their contribution to the treatment of this disease. Proposed recommendations appear as the result of a nominal consensus which was developed during 2019, and validated at the beginning of 2020.
    Language Spanish
    Publishing date 2021-01-08
    Publishing country Spain
    Document type English Abstract ; Journal Article
    ISSN 2659-6636
    ISSN (online) 2659-6636
    DOI 10.1016/j.opresp.2020.100079
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Eradication of

    Blanco-Aparicio, Marina / Saleta Canosa, Jesús Luis / Valiño López, Paz / Martín Egaña, María Teresa / Vidal García, Iria / Montero Martínez, Carmen

    Chronic respiratory disease

    2019  Volume 16, Page(s) 1479973119872513

    Abstract: The persistent isolation ... ...

    Abstract The persistent isolation of
    MeSH term(s) Administration, Inhalation ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/administration & dosage ; Bronchiectasis/complications ; Bronchiectasis/physiopathology ; Colistin/administration & dosage ; Disease Progression ; Dyspnea/etiology ; Female ; Forced Expiratory Volume ; Hospitalization ; Humans ; Male ; Middle Aged ; Prospective Studies ; Pseudomonas Infections/complications ; Pseudomonas Infections/drug therapy ; Pseudomonas aeruginosa ; Sputum/microbiology ; Vital Capacity ; Young Adult
    Chemical Substances Anti-Bacterial Agents ; Colistin (Z67X93HJG1)
    Language English
    Publishing date 2019-09-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 2211488-9
    ISSN 1479-9731 ; 1479-9723
    ISSN (online) 1479-9731
    ISSN 1479-9723
    DOI 10.1177/1479973119872513
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  10. Article ; Online: Screening Health-Promoting Compounds for Their Capacity to Induce the Activity of FOXO3.

    Jimenez, Lucia / Silva, Andreia / Calissi, Giampaolo / Grenho, Inês / Monteiro, Rita / Mayoral-Varo, Victor / Blanco-Aparicio, Carmen / Pastor, Joaquin / Bustos, Victor / Bracher, Franz / Megías, Diego / Ferreira, Bibiana I / Link, Wolfgang

    The journals of gerontology. Series A, Biological sciences and medical sciences

    2021  Volume 77, Issue 8, Page(s) 1485–1493

    Abstract: Several chemical compounds including natural products have been suggested as being effective against age-related diseases or as beneficial for a healthy life. On the other hand, forkhead box O (FOXO) proteins are emerging as key cellular components ... ...

    Abstract Several chemical compounds including natural products have been suggested as being effective against age-related diseases or as beneficial for a healthy life. On the other hand, forkhead box O (FOXO) proteins are emerging as key cellular components associated with extreme human longevity. FOXO proteins are mainly regulated by posttranslational modifications and as these modifications are reversible, activation and inactivation of FOXO are attainable through pharmacological treatment. Here, we questioned whether a panel of compounds with known health-beneficial properties has the capacity to induce the activity of FOXO factors. We show that resveratrol, a phytoalexin present in grapes and other food products, the amide alkaloid piperlongumine found in the fruit of the long pepper, and the plant-derived β-carboline compound harmine induced nuclear translocation of FOXO3. We also show that piperlongumine and harmine but not resveratrol activate FOXO-dependent transcription. We determined the half maximal effective concentration (EC50) values for resveratrol, piperlongumine, and harmine for FOXO translocation, and analyzed their inhibitory impact on chromosomal maintenance 1 (CRM1)-mediated nuclear export and the production of reactive oxygen species (ROS). We also used chemical biology approach and Western blot analysis to explore the underlying molecular mechanisms. We show that harmine, piperlongumine, and resveratrol activate FOXO3 independently of phosphoinositide 3-kinase (PI3K)/AKT signaling and the CRM1-mediated nuclear export. The effect of harmine on FOXO3 activity is at least partially mediated through the inhibition of dual-specificity tyrosine (Y) phosphorylationregulated kinase 1A (DYRK1A) and can be reverted by the inhibition of sirtuins (SIRTs).
    MeSH term(s) Dioxolanes/pharmacology ; Forkhead Box Protein O3/metabolism ; Harmine/pharmacology ; Humans ; Karyopherins ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Receptors, Cytoplasmic and Nuclear ; Resveratrol/pharmacology ; Exportin 1 Protein
    Chemical Substances Dioxolanes ; FOXO3 protein, human ; Forkhead Box Protein O3 ; Karyopherins ; Receptors, Cytoplasmic and Nuclear ; Harmine (4FHH5G48T7) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; piperlongumine (SGD66V4SVJ) ; Resveratrol (Q369O8926L)
    Language English
    Publishing date 2021-09-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1223643-3
    ISSN 1758-535X ; 1079-5006
    ISSN (online) 1758-535X
    ISSN 1079-5006
    DOI 10.1093/gerona/glab265
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