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  1. Article ; Online: Editorial: Role of hypoxia-inducible factors in metabolic immune cell adaptation during sepsis.

    Del Fresno, Carlos / Schulte, Leon Nicolas / López-Collazo, Eduardo

    Frontiers in immunology

    2023  Volume 14, Page(s) 1194504

    MeSH term(s) Humans ; Sepsis ; Inflammation ; Adaptation, Physiological ; Hypoxia
    Language English
    Publishing date 2023-04-18
    Publishing country Switzerland
    Document type Editorial ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1194504
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Induction of Endotoxin Tolerance Delays Acute Rejection in a Hindlimb Transplantation Model in Rats.

    Rubio Yanchuck, Mónica / Toledano, Víctor / Bonastre, Jorge / Diez, Jesús / Aguirre, Luis / López-Collazo, Eduardo

    Plastic and reconstructive surgery

    2022  Volume 149, Issue 2, Page(s) 216e–228e

    Abstract: Background: Acute rejection is seen in 85 percent of composite vascular allogeneic transplants despite long-term immunosuppression. Recently, it was reported that the induction of endotoxin tolerance prolonged heart allograft survival in mice. However, ... ...

    Abstract Background: Acute rejection is seen in 85 percent of composite vascular allogeneic transplants despite long-term immunosuppression. Recently, it was reported that the induction of endotoxin tolerance prolonged heart allograft survival in mice. However, it produced side effects in all the animals secondary to the inflammatory reaction. Galactomannan has shown endotoxin tolerance without this side effect in vitro. The authors hypothesized that galactomannan-induced endotoxin tolerance delays acute rejection in vascular allogeneic transplantation without the side effects produced by lipopolysaccharide.
    Methods: Twenty-four rat hindlimb transplants were divided into four groups according to the preconditioning received: control, lipopolysaccharide (0.16 ml/kg), galactomannan 72 hours before (galactomannan-72) (8 ml/kg), and galactomannan 24 hours before (galactomannan-24) (8 ml/kg). Median acute rejection time, weight loss, and diarrheal episodes were monitored. Blood samples were collected at 0, 7, 21, 30, 45, and 60 days. Plasma cytokines (i.e., tumor necrosis factor alpha, interferon gamma), peripheral chimerism, and lymphocyte percentages were analyzed.
    Results: Median allograft survival was 40 days (range, 40 to 44 days) in the control group, 68 days (range, 61 to 71 days) in the lipopolysaccharide group, and 70 days (range, 69 to 73 days) in both galactomannan groups (p = 0.001). Weight loss was higher in the lipopolysaccharide group (p < 0.001), as was the 83.3 percent rate of diarrheal episodes (control, 0 percent, p = 0.015; galactomannan-72, 0 percent, p = 0.015; and galactomannan-24, 16.7 percent, p = 0.02). Preconditioned rats had higher peripheral blood chimerism (lipopolysaccharide, 2.30 ± 0.13 percent; galactomannan-72, 2.63 ±1.46 percent; and galactomannan-24, 2.47 ± 0.19 percent) compared to the control group (2.06 ± 0.36 percent) (lipopolysaccharide, p = 0.04; galactomannan-72, p = 0.002; and galactomannan-24, p = 0.002).
    Conclusions: Induction of endotoxin tolerance delays acute rejection in the rat hindlimb transplantation model. Galactomannan preconditioning has no lipopolysaccharide side effects and was equally effective in delaying acute rejection.
    Clinical relevance statement: The contributions of this experimental work are very incipient. Although the use of galactomannan in clinical practice requires more studies to assess its safety, there is no doubt that immunomodulation may be one of the responses that solve the problem of long-term immunosuppression.
    MeSH term(s) Acute Disease ; Allografts/blood supply ; Animals ; Disease Models, Animal ; Endotoxin Tolerance ; Graft Rejection/etiology ; Hindlimb/blood supply ; Hindlimb/transplantation ; Rats ; Time Factors ; Transplantation, Homologous
    Language English
    Publishing date 2022-01-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 208012-6
    ISSN 1529-4242 ; 0032-1052 ; 0096-8501
    ISSN (online) 1529-4242
    ISSN 0032-1052 ; 0096-8501
    DOI 10.1097/PRS.0000000000008794
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Heat-killed

    Minute, Luna / Bergón-Gutiérrez, Marta / Mata-Martínez, Pablo / Fernández-Pascual, Jaime / Terrón, Verónica / Bravo-Robles, Laura / Bıçakcıoğlu, Gülce / Zapata-Fernández, Gabriela / Aguiló, Nacho / López-Collazo, Eduardo / Del Fresno, Carlos

    iScience

    2024  Volume 27, Issue 2, Page(s) 108869

    Abstract: Trained immunity (TI) represents a memory-like process of innate immune cells. TI can be initiated with various compounds such as fungal β-glucan or the tuberculosis vaccine, Bacillus Calmette-Guérin. Nevertheless, considering the clinical applications ... ...

    Abstract Trained immunity (TI) represents a memory-like process of innate immune cells. TI can be initiated with various compounds such as fungal β-glucan or the tuberculosis vaccine, Bacillus Calmette-Guérin. Nevertheless, considering the clinical applications of harnessing TI against infections and cancer, there is a growing need for new, simple, and easy-to-use TI inducers. Here, we demonstrate that heat-killed
    Language English
    Publishing date 2024-01-11
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2024.108869
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  4. Article ; Online: PSGL-1: a novel immune checkpoint driving T-cell dysfunction in obstructive sleep apnea.

    Díaz-García, Elena / García-Sánchez, Aldara / Alfaro, Enrique / López-Fernández, Cristina / Mañas, Eva / Cano-Pumarega, Irene / López-Collazo, Eduardo / García-Río, Francisco / Cubillos-Zapata, Carolina

    Frontiers in immunology

    2023  Volume 14, Page(s) 1277551

    Abstract: Introduction: Although higher incidence of cancer represents a major burden for obstructive sleep apnea (OSA) patients, the molecular pathways driving this association are not completely understood. Recently, the adhesion receptor P-selectin ... ...

    Abstract Introduction: Although higher incidence of cancer represents a major burden for obstructive sleep apnea (OSA) patients, the molecular pathways driving this association are not completely understood. Recently, the adhesion receptor P-selectin glycoprotein-1 (PSGL 1) has been identified as a novel immune checkpoint, which are recognized major hallmarks in several types of cancer and have revolutionized cancer therapy.
    Methods: The expression of PSGL-1 and its ligands VISTA and SIGLEC-5 was assessed in the leucocytes of OSA patients and control subjects exploring the role of intermittent hypoxia (IH) using
    Results: Data showed PSGL-1 expression is upregulated in the T-lymphocytes from patients with severe OSA, indicating a relevant role of hypoxemia mediated by intermittent hypoxia. Besides, results suggest an inhibitory role of PSGL-1 on T-cell proliferation capacity. Finally, the expression of SIGLEC-5 but not VISTA was increased in monocytes from OSA patients, suggesting a regulatory role of intermittent hypoxia.
    Discussion: In conclusion, PSGL-1 might constitute an additional immune checkpoint leading to T-cell dysfunction in OSA patients, contributing to the disruption of immune surveillance, which might provide biological plausibility to the higher incidence and aggressiveness of several tumors in these patients.
    MeSH term(s) Humans ; Hypoxia/etiology ; Hypoxia/genetics ; Hypoxia/immunology ; Membrane Glycoproteins/biosynthesis ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/immunology ; Neoplasms/etiology ; Neoplasms/genetics ; Neoplasms/immunology ; Sialic Acid Binding Immunoglobulin-like Lectins ; Sleep Apnea, Obstructive/complications ; Sleep Apnea, Obstructive/genetics ; Sleep Apnea, Obstructive/immunology ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism
    Chemical Substances Membrane Glycoproteins ; P-selectin ligand protein ; Sialic Acid Binding Immunoglobulin-like Lectins ; SIGLEC5 protein, human ; VSIR protein, human
    Language English
    Publishing date 2023-10-03
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1277551
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Simultaneous Targeting of IL-1-Signaling and IL-6-Trans-Signaling Preserves Human Pulmonary Endothelial Barrier Function During a Cytokine Storm-Brief Report.

    Colás-Algora, Natalia / Muñoz-Pinillos, Pablo / Cacho-Navas, Cristina / Avendaño-Ortiz, José / de Rivas, Gema / Barroso, Susana / López-Collazo, Eduardo / Millán, Jaime

    Arteriosclerosis, thrombosis, and vascular biology

    2023  Volume 43, Issue 11, Page(s) 2213–2222

    Abstract: Background: Systemic inflammatory diseases, such as sepsis and severe COVID-19, provoke acute respiratory distress syndrome in which the pathological hyperpermeability of the microvasculature, induced by uncontrolled inflammatory stimulation, causes ... ...

    Abstract Background: Systemic inflammatory diseases, such as sepsis and severe COVID-19, provoke acute respiratory distress syndrome in which the pathological hyperpermeability of the microvasculature, induced by uncontrolled inflammatory stimulation, causes pulmonary edema. Identifying the inflammatory mediators that induce human lung microvascular endothelial cell barrier dysfunction is essential to find the best anti-inflammatory treatments for critically ill acute respiratory distress syndrome patients.
    Methods: We have compared the responses of primary human lung microvascular endothelial cells to the main inflammatory mediators involved in cytokine storms induced by sepsis and SARS-CoV2 pulmonary infection and to sera from healthy donors and severely ill patients with sepsis. Endothelial barrier function was measured by electric cell-substrate impedance sensing, quantitative confocal microscopy, and Western blot.
    Results: The human lung microvascular endothelial cell barrier was completely disrupted by IL (interleukin)-6 conjugated with soluble IL-6R (IL-6 receptor) and by IL-1β (interleukin-1beta), moderately affected by TNF (tumor necrosis factor)-α and IFN (interferon)-γ and unaffected by other cytokines and chemokines, such as IL-6, IL-8, MCP (monocyte chemoattractant protein)-1 and MCP-3. The inhibition of IL-1 and IL-6R simultaneously, but not separately, significantly reduced endothelial hyperpermeability on exposing human lung microvascular endothelial cells to a cytokine storm consisting of 8 inflammatory mediators or to sera from patients with sepsis. Simultaneous inhibition of IL-1 and JAK (Janus kinase)-STAT (signal transducer and activator of transcription protein), a signaling node downstream IL-6 and IFN-γ, also prevented septic serum-induced endothelial barrier disruption.
    Conclusions: These findings strongly suggest a major role for both IL-6 trans-signaling and IL-1β signaling in the pathological increase in permeability of the human lung microvasculature and reveal combinatorial strategies that enable the gradual control of pulmonary endothelial barrier function in response to a cytokine storm.
    MeSH term(s) Humans ; Interleukin-6/metabolism ; Cytokine Release Syndrome ; Endothelial Cells/metabolism ; RNA, Viral/metabolism ; Lung/metabolism ; Interferon-gamma/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Respiratory Distress Syndrome ; COVID-19/metabolism ; Sepsis/metabolism ; Interleukin-1/metabolism
    Chemical Substances Interleukin-6 ; RNA, Viral ; Interferon-gamma (82115-62-6) ; Tumor Necrosis Factor-alpha ; Interleukin-1
    Language English
    Publishing date 2023-09-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1221433-4
    ISSN 1524-4636 ; 1079-5642
    ISSN (online) 1524-4636
    ISSN 1079-5642
    DOI 10.1161/ATVBAHA.123.319695
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Immune Response and COVID-19: A mirror image of Sepsis.

    López-Collazo, Eduardo / Avendaño-Ortiz, José / Martín-Quirós, Alejandro / Aguirre, Luis A

    International journal of biological sciences

    2020  Volume 16, Issue 14, Page(s) 2479–2489

    Abstract: The emergence of SARS-CoV-2 virus and its associated disease COVID-19 have triggered significant threats to public health, in addition to political and social changes. An important number of studies have reported the onset of symptoms compatible with ... ...

    Abstract The emergence of SARS-CoV-2 virus and its associated disease COVID-19 have triggered significant threats to public health, in addition to political and social changes. An important number of studies have reported the onset of symptoms compatible with pneumonia accompanied by coagulopathy and lymphocytopenia during COVID-19. Increased cytokine levels, the emergence of acute phase reactants, platelet activation and immune checkpoint expression are some of the biomarkers postulated in this context. As previously observed in prolonged sepsis, T-cell exhaustion due to SARS-CoV-2 and even their reduction in numbers due to apoptosis hinder the response to the infection. In this review, we synthesized the immune changes observed during COVID-19, the role of immune molecules as severity markers for patient stratification and their associated therapeutic options.
    MeSH term(s) Adrenal Cortex Hormones/therapeutic use ; Antiviral Agents/therapeutic use ; Betacoronavirus ; Biomarkers ; Blood Coagulation Disorders/immunology ; COVID-19 ; Coronavirus Infections/immunology ; Coronavirus Infections/physiopathology ; Cytokines/metabolism ; Humans ; Immune System ; Immunity, Innate ; Interferons/metabolism ; Lymphopenia/immunology ; Pandemics ; Phenotype ; Platelet Activation ; Pneumonia, Viral/immunology ; Pneumonia, Viral/physiopathology ; SARS-CoV-2 ; Sepsis/physiopathology
    Chemical Substances Adrenal Cortex Hormones ; Antiviral Agents ; Biomarkers ; Cytokines ; Interferons (9008-11-1)
    Keywords covid19
    Language English
    Publishing date 2020-07-09
    Publishing country Australia
    Document type Journal Article ; Review
    ZDB-ID 2179208-2
    ISSN 1449-2288 ; 1449-2288
    ISSN (online) 1449-2288
    ISSN 1449-2288
    DOI 10.7150/ijbs.48400
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  7. Article ; Online: Inherited Human BCL10 Deficiencies.

    Alsaidalani, Ashwag A / García-Solís, Blanca / Bukhari, Esraa / Van Den Rym, Ana / López-Collazo, Eduardo / Sánchez-Ramón, Silvia / Corvillo, Fernando / López-Lera, Alberto / de Andrés, Ana / Martínez-Barricarte, Rubén / Perez de Diego, Rebeca

    Journal of clinical immunology

    2023  Volume 44, Issue 1, Page(s) 13

    Abstract: Human BCL10 deficiency causes combined immunodeficiency with bone marrow transplantation as its only curative option. To date, there are four homozygous mutations described in the literature that were identified in four unrelated patients. Here, we ... ...

    Abstract Human BCL10 deficiency causes combined immunodeficiency with bone marrow transplantation as its only curative option. To date, there are four homozygous mutations described in the literature that were identified in four unrelated patients. Here, we describe a fifth patient with a novel mutation and summarize what we have learned about BCL10 deficiency. Due to the severity of the disease, accurate knowledge of its clinical and immunological characteristics is instrumental for early diagnosis and adequate clinical management of the patients.
    MeSH term(s) Humans ; B-Cell CLL-Lymphoma 10 Protein/genetics ; Bone Marrow Transplantation ; Immunologic Deficiency Syndromes/diagnosis ; Immunologic Deficiency Syndromes/genetics ; Immunologic Deficiency Syndromes/therapy ; Mutation/genetics
    Chemical Substances B-Cell CLL-Lymphoma 10 Protein ; BCL10 protein, human
    Language English
    Publishing date 2023-12-22
    Publishing country Netherlands
    Document type Case Reports ; Journal Article ; Review
    ZDB-ID 779361-3
    ISSN 1573-2592 ; 0271-9142
    ISSN (online) 1573-2592
    ISSN 0271-9142
    DOI 10.1007/s10875-023-01619-z
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  8. Article: Dried Blood Specimens as an Alternative Specimen for Immune Response Monitoring During HIV Infection: A Proof of Concept and Simple Method in a Pediatric Cohort.

    Rubio-Garrido, Marina / Avendaño-Ortiz, José / Ndarabu, Adolphe / Rubio, Carolina / Reina, Gabriel / López-Collazo, Eduardo / Holguín, África

    Frontiers in medicine

    2021  Volume 8, Page(s) 678850

    Abstract: Programs to prevent mother-to-child HIV transmission do not reduce the number of infants exposed during pregnancy and breastfeeding. HIV-exposed but uninfected children (HEU) present higher risk of morbidity and mortality than HIV-unexposed and ... ...

    Abstract Programs to prevent mother-to-child HIV transmission do not reduce the number of infants exposed during pregnancy and breastfeeding. HIV-exposed but uninfected children (HEU) present higher risk of morbidity and mortality than HIV-unexposed and uninfected children (UU). In this line, the study of immune biomarkers in HIV could improve prediction of disease progression, allowing to diminish comorbidity risk. Dried blood specimens (DBS) are an alternative to serum for collecting and transporting samples in countries with limited infrastructure and especially interesting for groups such as pediatrics, where obtaining a high sample volume is challenging. This study explores the usefulness of DBS for immune profile monitoring in samples from 30 children under clinical follow-up in Kinshasa: 10 HIV-infected (HIV+), 10 HEU, and 10 UU. We have measured the gene expression levels of 12 immune and inflammatory markers (CD14, IL-6, TNFα, HVEM, B7.1, HIF-1α, Siglec-10, IRAK-M, CD163, B7H5, PD-L1, and Galectin-9) in DBS samples by reverse transcription of total RNA and RT-qPCR. Principal component analysis, Kruskal-Wallis test, and Mann-Whitney test were performed in order to study group differences. HIV+ children presented significantly higher levels of seven biomarkers (CD14, IL-6 HVEM, B7.1, Siglec-10, HIF-1α, and CD163) than the UU group. In HEU, we found seven biomarkers significantly elevated (CD14, IL-6, HVEM, B7.1, Siglec-10, HIF-1α, and IRAK-M) vs. UU. Six biomarkers (CD14, IL-6, HVEM, B7.1, Siglec-10, and HIF-1α) showed a significantly higher expression in both HIV+ and HEU vs. UU, with HVEM and CD14 being significantly overexpressed among HIV+ vs. HEU. Our data reveal the utility of DBS for immune response monitoring. Moreover, significant differences in specific biomarker expression across groups strongly suggest the effect of HIV infection and/or HIV exposure on these immune biomarkers' expressions.
    Language English
    Publishing date 2021-06-15
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2021.678850
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  9. Article ; Online: SMAD4 Expression in Monocytes as a Potential Biomarker for Atherosclerosis Risk in Patients with Obstructive Sleep Apnea.

    Díaz-García, Elena / García-Sánchez, Aldara / Sánz-Rubio, David / Alfaro, Enrique / López-Fernández, Cristina / Casitas, Raquel / Mañas Baena, Eva / Cano-Pumarega, Irene / Cubero, Pablo / Marin-Oto, Marta / López-Collazo, Eduardo / Marin, José María / García-Río, Francisco / Cubillos-Zapata, Carolina

    International journal of molecular sciences

    2023  Volume 24, Issue 9

    Abstract: Obstructive sleep apnea (OSA) patients are at special risk of suffering atherosclerosis, leading to major cardiovascular diseases. Notably, the transforming growth factor (TGF-β) plays a crucial role in the development and progression of atherosclerosis. ...

    Abstract Obstructive sleep apnea (OSA) patients are at special risk of suffering atherosclerosis, leading to major cardiovascular diseases. Notably, the transforming growth factor (TGF-β) plays a crucial role in the development and progression of atherosclerosis. In this context, the central regulator of TGF-β pathway, SMAD4 (small mother against decapentaplegic homolog 4), has been previously reported to be augmented in OSA patients, which levels were even higher in patients with concomitant cardiometabolic diseases. Here, we analyzed soluble and intracellular SMAD4 levels in plasma and monocytes from OSA patients and non-apneic subjects, with or without early subclinical atherosclerosis (eSA). In addition, we used in vitro and ex vivo models to explore the mechanisms underlying SMAD4 upregulation and release. Our study confirmed elevated sSMAD4 levels in OSA patients and identified that its levels were even higher in those OSA patients with eSA. Moreover, we demonstrated that SMAD4 is overexpressed in OSA monocytes and that intermittent hypoxia contributes to SMAD4 upregulation and release in a process mediated by NLRP3. In conclusion, this study highlights the potential role of sSMAD4 as a biomarker for atherosclerosis risk in OSA patients and provides new insights into the mechanisms underlying its upregulation and release to the extracellular space.
    MeSH term(s) Humans ; Monocytes/metabolism ; Atherosclerosis/metabolism ; Hypoxia/metabolism ; Biomarkers/metabolism ; Sleep Apnea, Obstructive ; Smad4 Protein/genetics ; Smad4 Protein/metabolism
    Chemical Substances Biomarkers ; SMAD4 protein, human ; Smad4 Protein
    Language English
    Publishing date 2023-04-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24097900
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  10. Article ; Online: Thiosulfinate-Enriched

    Avendaño-Ortiz, José / Redondo-Calvo, Francisco Javier / Lozano-Rodríguez, Roberto / Terrón-Arcos, Verónica / Bergón-Gutiérrez, Marta / Rodríguez-Jiménez, Concepción / Rodríguez, Juan Francisco / Del Campo, Rosa / Gómez, Luis Antonio / Bejarano-Ramírez, Natalia / Pérez-Ortiz, José Manuel / López-Collazo, Eduardo

    International journal of molecular sciences

    2023  Volume 24, Issue 7

    Abstract: Garlic ( ...

    Abstract Garlic (
    MeSH term(s) Humans ; Antioxidants/pharmacology ; Garlic/metabolism ; Lipopolysaccharides/pharmacology ; Lipopolysaccharides/metabolism ; Monocytes/metabolism ; Sepsis/metabolism ; Tumor Necrosis Factor-alpha/metabolism
    Chemical Substances Antioxidants ; Lipopolysaccharides ; Tumor Necrosis Factor-alpha ; HIF1A protein, human
    Language English
    Publishing date 2023-03-25
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24076234
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