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1.
Int J Mol Sci ; 25(15)2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39125875

RESUMEN

Parasites have been associated with possible anticancer activity, including Trypanosoma cruzi, which has been linked to inhibiting the growth of solid tumors. To better understand this antitumor effect, we investigated the association of anti-T. cruzi antibodies with B cells of the acute lymphoblastic leukemia (ALL) SUPB15 cell line. The antibodies were generated in rabbits. IgGs were purified by affinity chromatography. Two procedures (flow cytometry (CF) and Western blot(WB)) were employed to recognize anti-T. cruzi antibodies on SUPB15 cells. We also used CF to determine whether the anti-T. cruzi antibodies could suppress SUPB15 cells. The anti-T. cruzi antibodies recognized 35.5% of the surface antigens of SUPB15. The complement-dependent cytotoxicity (CDC) results demonstrate the cross-suppression of anti-T. cruzi antibodies on up to 8.4% of SUPB15 cells. For the WB analysis, a band at 100 kDa with high intensity was sequenced using mass spectrometry, identifying the protein as nucleolin. This protein may play a role in the antitumor effect on T. cruzi. The anti-T. cruzi antibodies represent promising polyclonal antibodies that have the effect of tumor-suppressive cross-linking on cancer cells, which should be further investigated.


Asunto(s)
Anticuerpos Antiprotozoarios , Leucemia-Linfoma Linfoblástico de Células Precursoras , Trypanosoma cruzi , Trypanosoma cruzi/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Humanos , Línea Celular Tumoral , Animales , Conejos , Anticuerpos Antiprotozoarios/inmunología , Proteínas de Unión al ARN/inmunología , Proteínas de Unión al ARN/metabolismo , Nucleolina , Fosfoproteínas/inmunología , Fosfoproteínas/metabolismo
2.
Int J Mol Sci ; 25(11)2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38892345

RESUMEN

Overuse of antimicrobials has greatly contributed to the increase in the emergence of multidrug-resistant bacteria, a situation that hinders the control and treatment of infectious diseases. This is the case with urinary tract infections (UTIs), which represent a substantial percentage of worldwide public health problems, thus the need to look for alternatives for their control and treatment. Previous studies have shown the usefulness of autologous bacterial lysates as an alternative for the treatment and control of UTIs. However, a limitation is the high cost of producing individual immunogens. At the same time, an important aspect of vaccines is their immunogenic amplitude, which is the reason why they must be constituted of diverse antigenic components. In the case of UTIs, the etiology of the disease is associated with different bacteria, and even Escherichia coli, the main causal agent of the disease, is made up of several antigenic variants. In this work, we present results on the study of a bacterial lysate composed of 10 serotypes of Escherichia coli and by Klebsiella pneumoniae, Klebsiella aerogenes, Enterococcus faecalis, Proteus mirabilis, Citrobacter freundii, and Staphylococcus haemolyticus. The safety of the compound was tested on cells in culture and in an animal model, and its immunogenic capacity by analysing in vitro human and murine macrophages (cell line J774 A1). The results show that the polyvalent lysate did not cause damage to the cells in culture or alterations in the animal model used. The immunostimulatory activity assay showed that it activates the secretion of TNF-α and IL-6 in human macrophages and TNF-α in murine cells. The obtained results suggest that the polyvalent lysate evaluated can be an alternative for the treatment and control of chronic urinary tract infections, which will reduce the use of antimicrobials.


Asunto(s)
Infecciones Urinarias , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiología , Infecciones Urinarias/inmunología , Infecciones Urinarias/terapia , Animales , Humanos , Ratones , Escherichia coli , Femenino , Extractos Celulares/farmacología , Extractos Celulares/uso terapéutico , Lisados Bacterianos
3.
Eur J Immunol ; : e2350716, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38837757

RESUMEN

Immune mediators affect multiple biological functions of intestinal epithelial cells (IECs) and, like Paneth and Paneth-like cells, play an important role in intestinal epithelial homeostasis. IFN-γ a prototypical proinflammatory cytokine disrupts intestinal epithelial homeostasis. However, the mechanism underlying the process remains unknown. In this study, using in vivo and in vitro models we demonstrate that IFN-γ is spontaneously secreted in the small intestine. Furthermore, we observed that this cytokine stimulates mitochondrial activity, ROS production, and Paneth and Paneth-like cell secretion. Paneth and Paneth-like secretion downstream of IFN-γ, as identified here, is mTORC1 and necroptosis-dependent. Thus, our findings revealed that the pleiotropic function of IFN-γ also includes the regulation of Paneth cell function in the homeostatic gut.

4.
Rev. chil. obstet. ginecol. (En línea) ; Rev. chil. obstet. ginecol;89(3): 182-188, jun. 2024. tab
Artículo en Español | LILACS | ID: biblio-1569784

RESUMEN

El sangrado uterino anormal tiene una etiología variable, que va desde causas estructurales hasta causas funcionales, que se describen clásicamente en el acrónimo PALM-COEIN. No obstante, hay una pobre sensibilización de este síntoma como un marcador de enfermedades graves. En esta revisión se describe la relación de la hemorragia uterina anormal como síntoma clave o de presentación de malignidad hematológica, así como la posible relación con la hemofilia adquirida secundaria a neoplasia hematológica como causal del evento hemostático. Se realizó búsqueda en la literatura, con la mayoría de los artículos obtenidos de Medline, 24 de los cuales cumplieron con los objetivos para resolver la pregunta de investigación. Se encontraron diferentes malignidades hematológicas asociadas a sangrado uterino anormal, de las cuales la hemofilia adquirida y la trombocitopenia como potenciales causales de esta; la mayor correlación fue con leucemia, seguido de linfomas, y en menor cuantía la asociación con mieloma múltiple.


Abnormal uterine bleeding has a variable etiology, ranging from structural to functional causes, classically described by the acronym PALM-COEIN. However, there is poor awareness of this symptom as a marker of serious disease; in this review, we describe the relationship of abnormal uterine bleeding as a key symptom or debut of hematologic malignancy, as well as its possible relationship to acquired hemophilia secondary to hematologic neoplasia as causative of the hemostatic event. A literature search was performed, with most of the articles obtained from Medline, 24 of which met the objectives to solve the research question. Different hematological malignancies associated with abnormal uterine bleeding were found, of which acquired hemophilia and thrombocytopenia were found as potential causes; the highest correlation was with leukemia, followed by lymphomas, and to a lesser extent the association with multiple myeloma.


Asunto(s)
Humanos , Femenino , Hemorragia Uterina/etiología , Enfermedades Hematológicas/complicaciones , Leucemia/complicaciones , Hemofilia A/complicaciones
5.
Front Oncol ; 14: 1356581, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38567159

RESUMEN

Cervical cancer (CC) is a significant health problem, especially in low-income countries. Functional studies on the human papillomavirus have generated essential advances in the knowledge of CC. However, many unanswered questions remain. This mini-review discusses the latest results on CC pathogenesis, HPV oncogenesis, and molecular changes identified through next-generation technologies. Interestingly, the percentage of samples with HPV genome integrations correlates with the degree of the cervical lesions, suggesting a role in the development of CC. Also, new functions have been described for the viral oncoproteins E5, E6, and E7, resulting in the acquisition and maintenance of cancer hallmarks, including proliferation, immune response evasion, apoptosis, and genomic instability. Remarkably, E5 oncoprotein affects signaling pathways involved in the expression of interferon-induced genes and EGFR-induced proliferation, while E6 and E7 oncoproteins regulate the DNA damage repair and cell cycle continuity pathways. Furthermore, next-generation technologies provide vast amounts of information, increasing our knowledge of changes in the genome, transcriptome, proteome, metabolome, and epigenome in CC. These studies have identified novel molecular traits associated with disease susceptibility, degree of progression, treatment response, and survival as potential biomarkers and therapeutic targets.

6.
Polymers (Basel) ; 15(20)2023 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-37896349

RESUMEN

In this study, we synthesized and characterized pH-responsive Chitosan-AgCl-doped ZnO hybrid hydrogels and evaluated their potential for loading aquaculture bioactive compounds, and assessed their antimicrobial properties against a threatening pathogen associated with disease across a broad spectrum of warm water fish and invertebrates. Hydrogel characterization consisted of assessing morphology via SEM, composition via EDS, hydrogels' network components interactions via FT-IR and pH response through swelling behavior determinations. The swelling characterization of the synthesized hydrogels demonstrated a pH-responsive behavior, showing that low pH values caused the hydrogel polymeric network to expand and capture more of the aqueous solution. These characteristics make the synthesized hydrogels suitable for the encapsulation and controlled release of drugs and bioactive compounds in aquaculture. Chitosan_ZnO hybrid hydrogels showed great antimicrobial activity against Vibrio harveyi, even better than that of loaded PB hydrogels. Here, we provide evidence for the potential capacity of Chitosan_ZnO hybrid hydrogels for the preventive and curative treatment of diseases that impact aquaculture animal health and prevent drug resistance by bacteria.

7.
Rev Colomb Psiquiatr (Engl Ed) ; 52(3): 245-250, 2023.
Artículo en Inglés, Español | MEDLINE | ID: mdl-37863769

RESUMEN

INTRODUCTION: The detection of anxiety symptoms among health workers who care for patients infected with COVID-19 is a current priority. Fast and valid instruments are required for this population group. The objective is to establish the construct validity and reliability of the Generalised Anxiety Disorder (GAD-7) scale in Colombian doctors during the COVID-19 lockdown. METHODS: E-health study, in which cross-sectional data were collected online (n = 1030) from 610 COVID doctors and 420 non-COVID doctors, during the Colombian lockdown, between 20 April and 10 August 2020. Each subject was contacted, and they confirmed their participation, identity and professional role. RESULTS: A single factor factorial structure was found, made up of the 7 items of the instrument, which managed to explain 70% of the variance. The goodness of fit indices (RMSEA = 0.080; CFI = 0.995; SRMR = 0.053; p < 0.001) showed an "acceptable" unidimensionality and adequate factor loadings in each item of the GAD-7, >0.070. Finally, the internal consistency of the instrument was good, with a Cronbach's alpha of 0.920 (95%IC, 8.80-9.71). CONCLUSIONS: The GAD-7 is an instrument that presents adequate indicators of validity and reliability. It is an excellent tool that is reliable and easy and fast to use for the detection of generalised anxiety symptoms in medical personnel caring (or not) for patients infected with COVID-19.


Asunto(s)
COVID-19 , Cuestionario de Salud del Paciente , Humanos , Reproducibilidad de los Resultados , Estudios Transversales , Colombia , Pandemias , Encuestas y Cuestionarios , Psicometría , Control de Enfermedades Transmisibles
8.
Rev. colomb. psiquiatr ; 52(3)sept. 2023.
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1536146

RESUMEN

Introducción: La detección de síntomas de ansiedad entre el personal sanitario que atiende a pacientes contagiados de COVID-19 es una prioridad actual. Se requieren instrumentos rápidos y válidos para esta población. El objetivo es establecer la validez de constructo y la confiabilidad de la Escala de Ansiedad Generalizada (GAD-7) en médicos colombianos durante la cuarentena por la COVID-19. Métodos: Estudio eSalud, en el que se recopilaron datos transversales en línea (n = 1.030) de 610 médicos de COVID y 420 no de COVID durante la cuarentena colombiana, entre el 20 de abril y el 10 de agosto de 2020. Se contactó con cada sujeto, que confirmó participación, identidad y función profesional. Resultados: Se encontró una estructura factorial de 1 solo factor, conformado por los 7 ítems del instrumento, que logró explicar el 70% de la varianza. Los índices de bondad de ajuste (RMSEA = 0,080; CFI = 0,995; SRMR = 0,053; p 0,07. Por último, la consistencia interna del instrumento fue buena, con alfa de Cronbach = 0,920 (IC95%,8,80-9,71). Conclusiones: El GAD-7 es un instrumento que presenta indicadores adecuados de validez y confiabilidad. Es un excelente instrumento, confiable, fácil y rápido de usar para la detección de los síntomas de ansiedad generalizada en personal médico, atienda o no a pacientes contagiados de COVID-19.


Introduction: The detection of anxiety symptoms among health workers who care for patients infected with COVID-19 is a current priority. Fast and valid instruments are required for this population group. The objective is to establish the construct validity and reliability of the Generalized Anxiety Disorder (GAD-7) scale in Colombian doctors during the COVID-19 lockdown. Methods: E-health study, in which cross-sectional data were collected online (n = 1,030) from 610 COVID doctors and 420 non-COVID doctors, during the Colombian lockdown, between 20 April and 10 August 2020. Each subject was contacted, and they confirmed their participation, identity and professional role. Results: A single factor factorial structure was found, made up of the 7 items of the instrument, which managed to explain 70% of the variance. The goodness of fit indices (RMSEA = 0.080; CFI = 0.995; SRMR = 0.053; p 0.070. Finally, the internal consistency of the instrument was good, with a Cronbach's alpha of 0.920 (95%IC, 8.80-9.71). Conclusions:The GAD-7 is an instrument that presents adequate indicators of validity and reliability. It is an excellent tool that is reliable and easy and fast to use for the detection of generalised anxiety symptoms in medical personnel caring (or not) for patients infected with COVID-19.

9.
J Leukoc Biol ; 113(3): 315-325, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36808495

RESUMEN

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy that is still fatal in many cases. T cell blasts are characterized by hyperactivation and strong proliferative and migratory capacities. The chemokine receptor CXCR4 is involved in mediating malignant T cell properties, and cortactin has been shown to control CXCR4 surface localization in T-ALL cells. We have previously shown that cortactin overexpression is correlated with organ infiltration and relapse in B-ALL. However, the role of cortactin in T cell biology and T-ALL remains elusive. Here, we analyzed the functional relevance of cortactin for T cell activation and migration and the implications for T-ALL development. We found that cortactin is upregulated in response to T cell receptor engagement and recruited to the immune synapse in normal T cells. Loss of cortactin caused reduced IL-2 production and proliferation. Cortactin-depleted T cells showed defects in immune synapse formation and migrated less due to impaired actin polymerization in response to T cell receptor and CXCR4 stimulation. Leukemic T cells expressed much higher levels of cortactin compared to normal T cells that correlated with greater migratory capacity. Xenotransplantation assays in NSG mice revealed that cortactin-depleted human leukemic T cells colonized the bone marrow significantly less and failed to infiltrate the central nervous system, suggesting that cortactin overexpression drives organ infiltration, which is a major complication of T-ALL relapse. Thus, cortactin could serve as a potential therapeutic target for T-ALL and other pathologies involving aberrant T cell responses.


Asunto(s)
Cortactina , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Animales , Ratones , Linfocitos T/metabolismo , Leucocitos , Recurrencia , Movimiento Celular/fisiología
10.
J Leukoc Biol ; 113(1): 1-10, 2023 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-36822163

RESUMEN

Hyperinflammation present in individuals with severe COVID-19 has been associated with an exacerbated cytokine production and hyperactivated immune cells. Endoplasmic reticulum stress leading to the unfolded protein response has been recently reported as an active player in inducing inflammatory responses. Once unfolded protein response is activated, GRP78, an endoplasmic reticulum-resident chaperone, is translocated to the cell surface (sGRP78), where it is considered a cell stress marker; however, its presence has not been evaluated in immune cells during disease. Here we assessed the presence of sGRP78 on different cell subsets in blood samples from severe or convalescent COVID-19 patients. The frequency of CD45+sGRP78+ cells was higher in patients with the disease compared to convalescent patients. The latter showed similar frequencies to healthy controls. In patients with COVID-19, the lymphoid compartment showed the highest presence of sGRP78+ cells versus the myeloid compartment. CCL2, TNF-α, C-reactive protein, and international normalized ratio measurements showed a positive correlation with the frequency of CD45+sGRP78+ cells. Finally, gene expression microarray data showed that activated T and B cells increased the expression of GRP78, and peripheral blood mononuclear cells from healthy donors acquired sGRP78 upon activation with ionomycin and PMA. Thus, our data highlight the association of sGRP78 on immune cells in patients with severe COVID-19.


Asunto(s)
COVID-19 , Chaperón BiP del Retículo Endoplásmico , Humanos , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Leucocitos Mononucleares/metabolismo , COVID-19/metabolismo , Chaperonas Moleculares/genética , Retículo Endoplásmico/metabolismo , Estrés del Retículo Endoplásmico
12.
J Proteomics ; 273: 104809, 2023 02 20.
Artículo en Inglés | MEDLINE | ID: mdl-36587729

RESUMEN

Immunological mechanisms of non-IgE-mediated cow's milk protein allergy (CMPA) are not well understood. Such a circumstance requires attention with the aim of discovering new biomarkers that could lead to better diagnostic assays for early treatment. Here, we sought both to investigate the mechanism that underlies non-IgE-mediated CMPA and to identify cow's milk immunoreactive proteins in a Mexican pediatric patient group (n = 34). Hence, we determined the IgE and IgG1-4 subclass antibody levels against cow's milk proteins (CMP) by ELISA. Then, we performed 2D-Immunoblots using as first antibody immunoglobulins in the patients'serum that bound specifically against CMP together with CMP enrichment by ion-exchange chromatography. Immunoreactive proteins were identified by mass spectrometry-based proteomics. The serological test confirmed absence of specific IgE in the CMPA patients but showed significant increase in antigen-specific IgG1. Additionally, we identified 11 proteins that specifically bound to IgG1. We conclude that the detection of specific IgG1 together with an immunoproteomics approach is highly relevant to the understanding of CMPA's physiopathology and as a possible aid in making a prognosis since current evidence indicates IgG1 occurrence as an early signal of potential risk toward development of IgE-mediated food allergy. SIGNIFICANCE: Allergies are one of the most studied topics in the field of public health and novel protein allergens are found each year. Discovery of new principal and regional allergens has remarkable repercussions in precise molecular diagnostics, prognostics, and more specific immunotherapies. In this context, specific IgE is widely known to mediate physiopathology; however, allergies whose mechanism does not involve this immunoglobulin are poorly understood although their incidence has increased. Therefore, accurate diagnosis and adequate treatment are delayed with significant consequences on the health of pediatric patients. The study of type and subtypes of immunoglobulins associated with the immunoreactivity of cow's milk proteins together with an immunoproteomics approach allows better comprehension of physiopathology, brings the opportunity to discover new potential cow's milk protein allergens and may help in prognosis prediction (IgG1 occurrence as an early signal of possible risk toward development of IgE-mediated food allergy).


Asunto(s)
Hipersensibilidad a los Alimentos , Hipersensibilidad a la Leche , Animales , Femenino , Bovinos , Hipersensibilidad a la Leche/diagnóstico , Inmunoglobulina E , Hipersensibilidad a los Alimentos/diagnóstico , Alérgenos , Proteínas de la Leche , Inmunoglobulina G
13.
Front Immunol ; 13: 979749, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36059446

RESUMEN

Mucosal innate immunity functions as the first line of defense against invading pathogens. Members of the IL-1 family are key cytokines upregulated in the inflamed mucosa. Inflammatory cytokines are regulated by limiting their function and availability through their activation and secretion mechanisms. IL-1 cytokines secretion is affected by the lack of a signal peptide on their sequence, which prevents them from accessing the conventional protein secretion pathway; thus, they use unconventional protein secretion pathways. Here we show in mouse macrophages that LPS/ATP stimulation induces cytokine relocalization to the plasma membrane, and conventional secretion blockade using monensin or Brefeldin A triggers no IL-36γ accumulation within the cell. In silico modeling indicates IL-36γ can pass through both the P2X7R and Gasdermin D pores, and both IL-36γ, P2X7R and Gasdermin D mRNA are upregulated in inflammation; further, experimental blockade of these receptors' limits IL-36γ release. Our results demonstrate that IL-36γ is secreted mainly by an unconventional pathway through membrane pores formed by P2X7R and Gasdermin D.


Asunto(s)
Inmunidad Mucosa , Proteínas de Unión a Fosfato/metabolismo , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Animales , Transporte Biológico , Citocinas/metabolismo , Interleucina-1 , Ratones
14.
Front Cell Infect Microbiol ; 12: 887647, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35832378

RESUMEN

Quinoxalines are heterocyclic compounds that contain a benzene ring and a pyrazine ring. The oxidation of both nitrogen of the pyrazine ring results in quinoxaline derivatives (QdNO), which exhibit a variety of biological properties, including antiparasitic activity. However, its activity against Entamoeba histolytica, the protozoan that causes human amebiasis, is poorly understood. Recently, our group reported that various QdNOs produce morphological changes in E. histolytica trophozoites, increase reactive oxygen species, and inhibit thioredoxin reductase activity. Notably, T-001 and T-017 derivatives were among the QdNOs with the best activity. In order to contribute to the characterization of the antiamebic effect of QdNOs, in this work we analyzed the proteomic profile of E. histolytica trophozoites treated with the QdNOs T-001 and T-017, and the results were correlated with functional assays. A total number of 163 deregulated proteins were found in trophozoites treated with T-001, and 131 in those treated with T-017. A set of 21 overexpressed and 24 under-expressed proteins was identified, which were mainly related to cytoskeleton and intracellular traffic, nucleic acid transcription, translation and binding, and redox homeostasis. Furthermore, T-001 and T-017 modified the virulence of trophozoites, since they altered their erythrophagocytosis, migration, adhesion and cytolytic capacity. Our results show that in addition to alter reactive oxygen species, and thioredoxin reductase activity, T-001 and T-017 affect essential functions related to the actin cytoskeleton, which eventually affects E. histolytica virulence and survival.


Asunto(s)
Entamoeba histolytica , Animales , Entamoeba histolytica/metabolismo , Humanos , Proteómica , Pirazinas , Quinoxalinas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Reductasa de Tiorredoxina-Disulfuro/metabolismo , Reductasa de Tiorredoxina-Disulfuro/farmacología , Trofozoítos/metabolismo
15.
J Immunol Res ; 2022: 2909487, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35402623

RESUMEN

The process by which blood cells are generated has been widely studied in homeostasis and during pathogen-triggered inflammatory response. Recently, murine lungs have been shown to be a significant source of hematopoietic progenitors in a process known as extramedullary hematopoiesis. Using multiparametric flow cytometry, we have identified mesenchymal, endothelial, and hematopoietic progenitor cells that express the secreted small protein Isthmin 1 (ISM1). Further characterization of hematopoietic progenitor cells indicated that ISM1+ Lineage- Sca-1+ c-kit+ (ISM1+ LSK) cells are enriched in short-term hematopoietic stem cells (ST-HSCs). Moreover, most Sca-1+ ISM1+ cells express the residence marker CD49a, and this correlated with their localization in the extravascular region of the lung, indicating that ISM1+ cells are lung-resident cells. We also observed that ISM1+ cells express TLR4, TLR5, and TLR9, and, in a mouse model of sepsis induced by P. aeruginosa, we observed that all the LSK and ISM1+LSK cells were affected. We conclude that ISM1 is a novel biomarker associated with progenitor-like cells. ISM1+ cells are involved in the response to a bacterial challenge, suggesting an association between ISM1-producing cells and dangerous inflammatory responses like sepsis.


Asunto(s)
Células Madre Hematopoyéticas , Sepsis , Animales , Hematopoyesis , Homeostasis , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Pulmón/metabolismo , Ratones , Ratones Endogámicos C57BL , Proteínas , Sepsis/metabolismo
16.
J Interferon Cytokine Res ; 42(2): 49-61, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35171706

RESUMEN

The interleukin (IL)-1 superfamily of cytokines comprises 11 pro- and anti-inflammatory cytokines, which play essential roles during the immune response. Several pathogenic pathways are initiated by IL-1RL2 (interleukin 1 receptor-like 2) signaling, also known as IL-36R, in the skin, lungs, and gut. IL-36 cytokines promote the secretion of proinflammatory cytokines and chemokines, upregulation of antimicrobial peptides, proliferation mediators, and adhesion molecules on endothelial cells. In addition, the IL-36-IL-1RL2 axis has an essential role against viral infections, including a potential role in COVID-19 pathology. The evidence presented in this review highlights the importance of the axis IL-36-IL-1RL2 in the development of several inflammation-related diseases and the healing process. It suggests that IL-1RL2 ligands have specific roles depending on the tissue or cell source. However, there is still much to discover about this cytokine family, their functions in other organs, and how they accomplish a dual effect in inflammation and healing.


Asunto(s)
Inflamación/fisiopatología , Receptores de Interleucina-1/fisiología , Animales , COVID-19/fisiopatología , Síndrome de Liberación de Citoquinas/fisiopatología , Citocinas/fisiología , Interacciones Huésped-Patógeno , Humanos , Interleucina-1/fisiología , Interleucinas/clasificación , Intestinos/metabolismo , Intestinos/patología , Ligandos , Pulmón/metabolismo , Pulmón/patología , Sistema de Señalización de MAP Quinasas , Ratones , FN-kappa B/metabolismo , Dominios Proteicos , Receptores de Interleucina/clasificación , Receptores de Interleucina-1/agonistas , Receptores de Interleucina-1/antagonistas & inhibidores , Receptores de Interleucina-1/química , SARS-CoV-2 , Transducción de Señal , Piel/metabolismo , Piel/patología
17.
J Hum Hypertens ; 36(7): 640-650, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-34218268

RESUMEN

Hypertension (HTN) causes end-organ damage and is a major cause of morbidity and mortality globally. Recent studies suggested blood cells participate in the maintenance of HTN. Platelets-anucleated cell fragments derived from megakaryocytes-exert diverse functions, including their well-characterized role in the formation of hemostatic clots. However, platelets from patients with HTN exhibit altered membrane lipid and protein compositions that impact platelet function and lead to formation of aggregates and vascular obstructions. Here, for the first time, we have identified, by proteomic analyses, the most relevant 11 proteins that show the greatest difference in their expression in platelets derived from patients with HTN, in comparison with those from normotensive individuals. These proteins are involved in cytoskeletal organization and the coagulation cascade that contributes to platelet activation, release of granule contents, and aggregation, which culminate in thrombus formation. These results have important implications in our understanding of the molecular mechanisms associated with the development of HTN, and in consequence, the development of new strategies to counteract the cardiovascular disorders associated with constitutive activation of platelets in HTN.


Asunto(s)
Hipertensión , Trombosis , Plaquetas , Humanos , Hipertensión/metabolismo , Megacariocitos/metabolismo , Activación Plaquetaria , Proteómica , Trombosis/metabolismo
18.
Rev. chil. obstet. ginecol. (En línea) ; Rev. chil. obstet. ginecol;86(5): 485-491, oct. 2021. tab
Artículo en Español | LILACS | ID: biblio-1388686

RESUMEN

INTRODUCCIÓN: Se ha documentado la asociación del síndrome de ovario poliquístico con alteraciones metabólicas y enfermedades cardiovasculares. Su relación con trastornos autoinmunitarios no está claramente establecida, pero se ha encontrado una importante prevalencia de desórdenes tiroideos en pacientes con síndrome de ovario poliquístico. OBJETIVO: Describir las diferentes teorías existentes que puedan explicar la relación entre hipotiroidismo y síndrome de ovario poliquístico, junto con su posible impacto en la morbilidad asociada. Método: Se realizó una búsqueda en PubMed y LILACS con las palabras clave "Polycystic ovary síndrome", "Hypotyroidism", "thyroid disease" y sus respectivos términos en español, durante julio de 2020. Resultados: Se seleccionaron 51 artículos relacionados con el tema, publicados en los últimos 10 años. La fisiopatogenia entre ambos trastornos no está claramente establecida. Se ha encontrado un importante impacto metabólico en este grupo de pacientes y se considera que su riesgo cardiovascular podría estar aumentado. CONCLUSIONES: Al considerarse la prevalencia significativa y las complicaciones que tanto a corto como a largo plazo podrían tener las mujeres con ambas alteraciones, se hace necesario discutir la necesidad de la exclusión del hipotiroidismo de los criterios diagnósticos aplicados para el síndrome, la tamización temprana y el estudio de las implicaciones terapéuticas que trae su abordaje.


INTRODUCTION: The association of polycystic ovary syndrome with other metabolic disorders and cardiovascular diseases has been documented; nevertheless, its relationship with autoimmune disorders is not clearly established, however, an important prevalence of thyroid disorders has been found in this group of patients. OBJECTIVE: To describe the different existing theories that can explain the relationship between hypothyroidism and polycystic ovary syndrome along with its possible impact on associated morbidities. Method: A search was conducted in PubMed and LILACS with the keywords of "Polycystic ovary syndrome", "Hypothyroidism", "Thyroid disease" and with its respective Spanish terms, in July 2020. Results: 51 articles related to the subject were selected, published in the last 10 years. The pathogenesis between both disorders is not clearly established. An important impact has been found at the metabolic level in this group of patients and it is considered that their cardiovascular risk could be increased. CONCLUSIONS: Considering the significant prevalence and complications that both short and long term, women with both alterations could have, it is necessary to discuss the need for the exclusion of hypothyroidism from the diagnostic criteria applied for the syndrome, early screening of the syndrome, and the study of the therapeutic implications that its approach brings.


Asunto(s)
Humanos , Femenino , Síndrome del Ovario Poliquístico/fisiopatología , Síndrome del Ovario Poliquístico/epidemiología , Hipotiroidismo/fisiopatología , Hipotiroidismo/epidemiología
19.
Artículo en Español | MEDLINE | ID: mdl-34230699

RESUMEN

Introduction: The detection of anxiety symptoms among health workers who care for patients infected with COVID-19 is a current priority. Fast and valid instruments are required for this population group. The objective is to establish the construct validity and reliability of the Generalised Anxiety Disorder (GAD-7) scale in Colombian doctors during the COVID-19 lockdown.Methods: E-health study, in which cross-sectional data were collected online (n=1,030) from 610 COVID doctors and 420 non-COVID doctors, during the Colombian lockdown, between 20 April and 10 August 2020. Each subject was contacted, and they confirmed their participation, identity and professional role.Results: A single factor factorial structure was found, made up of the 7 items of the instrument, which managed to explain 70% of the variance. The goodness of fit indices (RMSEA = 0.080; CFI = 0.995; SRMR = 0.053; p <0.001) showed an "acceptable" unidimensionality and adequate factor loadings in each item of the GAD-7, >0.070. Finally, the internal consistency of the instrument was good, with a Cronbach's alpha of 0.920 (95%IC, 8.80-9.71).Conclusions: The GAD-7 is an instrument that presents adequate indicators of validity and reliability. It is an excellent tool that is reliable and easy and fast to use for the detection of generalised anxiety symptoms in medical personnel caring (or not) for patients infected with COVID-19.

20.
Med. UIS ; 33(3): 21-28, sep.-dic. 2020. tab, graf
Artículo en Español | LILACS | ID: biblio-1360572

RESUMEN

Resumen El síndrome de ovario poliquístico, es la alteración endocrina metabólica más frecuente en mujeres en edad fértil, teniendo implicaciones a nivel reproductivo, metabólico, cardiovascular y psicosocial. Actualmente, su sobrediagnóstico corresponde a una problemática común derivada de la heterogeneidad en la aplicación de los criterios actualmente avalados para su hallazgo, lo que ha contribuido en el incremento de tratamientos innecesarios, así como los efectos negativos en la calidad de vida y el bienestar de las pacientes falsamente calificadas con este trastorno. Se realizó una búsqueda en PubMed-MENDELEY y Ovid entre los meses de Febrero a Abril del 2020, obteniendo 43 artículos relacionados con el tema, publicados en los últimos 10 años. El conocimiento por parte del personal médico capacitado sobre los consensos actuales para la correcta evaluación del síndrome y el estudio individualizado de cada caso, corresponden las medidas más apropiadas para la reducción del sobrediagnóstico. MÉD.UIS.2020;33(3):21-28


Abstract Polycystic ovary syndrome is the most frequent metabolic endocrine disorder in women of childbearing age, having implications at both the reproductive, metabolic, cardiovascular and psychosocial levels. Currently, its overdiagnosis corresponds to a common problem derived from the heterogeneity in the application of the criteria currently endorsed for its discovery, which has contributed to the increase in unnecessary treatments, as well as the negative effects on the quality of life and well-being of falsely rated patients with this disorder. A search was made in PubMed-MENDELEY and Ovid between the months of February to April of 2020, obtaining 43 articles related to the topic, published in the last 10 years. The knowledge on the part of the trained medical personnel about the current consensuses for the correct evaluation of the syndrome and the individualized study of each case, correspond to the most appropriate measures for the reduction of this event. MÉD.UIS.2020;33(3):21-28


Asunto(s)
Humanos , Femenino , Síndrome del Ovario Poliquístico , Hiperandrogenismo , Sobrediagnóstico , Anovulación
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