Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 177.468
Filtrar
1.
Science ; 373(6551)2021 07 09.
Artículo en Inglés | MEDLINE | ID: mdl-34244384

RESUMEN

Children with Down syndrome have a 150-fold increased risk of developing myeloid leukemia, but the mechanism of predisposition is unclear. Because Down syndrome leukemogenesis initiates during fetal development, we characterized the cellular and developmental context of preleukemic initiation and leukemic progression using gene editing in human disomic and trisomic fetal hematopoietic cells and xenotransplantation. GATA binding protein 1 (GATA1) mutations caused transient preleukemia when introduced into trisomy 21 long-term hematopoietic stem cells, where a subset of chromosome 21 microRNAs affected predisposition to preleukemia. By contrast, progression to leukemia was independent of trisomy 21 and originated in various stem and progenitor cells through additional mutations in cohesin genes. CD117+/KIT proto-oncogene (KIT) cells mediated the propagation of preleukemia and leukemia, and KIT inhibition targeted preleukemic stem cells.


Asunto(s)
Proteínas de Ciclo Celular/genética , Síndrome de Down/genética , Factor de Transcripción GATA1/genética , Células Madre Hematopoyéticas/fisiología , Leucemia Mieloide/genética , Preleucemia/genética , Animales , Antígenos CD34/análisis , Proteínas de Ciclo Celular/metabolismo , Linaje de la Célula , Proliferación Celular , Transformación Celular Neoplásica , Proteínas Cromosómicas no Histona/genética , Cromosomas Humanos Par 21/genética , Cromosomas Humanos Par 21/metabolismo , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Síndrome de Down/complicaciones , Femenino , Factor de Transcripción GATA1/metabolismo , Hematopoyesis , Trasplante de Células Madre Hematopoyéticas , Xenoinjertos , Humanos , Leucemia Mieloide/metabolismo , Leucemia Mieloide/patología , Hígado/embriología , Masculino , Megacariocitos/fisiología , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Mutación , Preleucemia/metabolismo , Preleucemia/patología , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-kit/análisis , Proteínas Proto-Oncogénicas c-kit/antagonistas & inhibidores
2.
J Allergy Clin Immunol Pract ; 9(7): 2567-2576, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34246433

RESUMEN

Acute exacerbations cause significant morbidity and mortality in children with asthma worldwide. Although exacerbations can be minor and transient, in some children they are recurrent and significantly adversely impact quality of life. Children with frequent exacerbations account for a disproportionate amount of unscheduled care in nonprimary health facilities. Frequent exacerbators are often prescribed controller medications, but poor adherence is common. Major predictors for asthma exacerbations include genetic, social, comorbid, biological, and environmental factors. Although virus infections are a key trigger for exacerbations, other environmental factors also significantly increase risk. A previous exacerbation is a major risk factor for future exacerbations and thus identifies children to target for prevention of future episodes. In this review, we discuss both modifiable and fixed factors associated with asthma exacerbations, how to assess children for risk, and which pharmacological and nonpharmacological interventions may be of benefit. Finally, we review the current evidence around treatment within the outpatient setting for an emerging exacerbation.


Asunto(s)
Asma , Calidad de Vida , Atención Ambulatoria , Asma/tratamiento farmacológico , Asma/epidemiología , Niño , Progresión de la Enfermedad , Humanos , Pacientes Ambulatorios
3.
Curr Allergy Asthma Rep ; 21(6): 38, 2021 07 14.
Artículo en Inglés | MEDLINE | ID: mdl-34259961

RESUMEN

PURPOSE OF REVIEW: Increasing knowledge of the pathogenesis of the SARS-CoV-2 infection and the complex interaction between host and viral factors have allowed clinicians to stratify the severity of COVID-19 infection. Epidemiological data has also helped to model viral carriage and infectivity. This review presents a comprehensive summary of the pathophysiology of COVID-19, the mechanisms of action of the SARS-CoV-2 virus, and the correlation with the clinical and biochemical characteristics of the disease. RECENT FINDINGS: ACE2 and TMPRSS2 receptors have emerged as a key player in the mechanism of infection of SARS-CoV-2. Their distribution throughout the body has been shown to impact the organ-specific manifestations of COVID-19. The immune-evasive and subsequently immunoregulative properties of SARS-CoV-2 are also shown to be implicated in disease proliferation and progression. Information gleaned from the virological properties of SARS-CoV-2 is consistent with and reflects the clinical behavior of the COVID-19 infection. Further study of specific clinical phenotypes and severity classes of COVID-19 may assist in the development of targeted therapeutics to halt progression of disease from mild to moderate-severe. As the understanding of the pathophysiology and mechanism of action of SARS-CoV-2 continues to grow, it is our hope that better and more effective treatment options continue to emerge.


Asunto(s)
COVID-19/fisiopatología , SARS-CoV-2/patogenicidad , Enzima Convertidora de Angiotensina 2/metabolismo , COVID-19/epidemiología , COVID-19/inmunología , COVID-19/virología , Progresión de la Enfermedad , Humanos , Evasión Inmune , Especificidad de Órganos , SARS-CoV-2/inmunología , Serina Endopeptidasas/metabolismo , Índice de Severidad de la Enfermedad , Internalización del Virus
4.
BMC Infect Dis ; 21(1): 677, 2021 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-34256735

RESUMEN

BACKGROUND: SARS-CoV-2 has swept across the globe, causing millions of deaths worldwide. Though most survive, many experience symptoms of COVID-19 for months after acute infection. Successful prevention and treatment of acute COVID-19 infection and its associated sequelae is dependent on in-depth knowledge of viral pathology across the spectrum of patient phenotypes and physiologic responses. Longitudinal biobanking provides a valuable resource of clinically integrated, easily accessed, and quality-controlled samples for researchers to study differential multi-organ system responses to SARS-CoV-2 infection, post-acute sequelae of COVID-19 (PASC), and vaccination. METHODS: Adults with a history of a positive SARS-CoV-2 nasopharyngeal PCR are actively recruited from the community or hospital settings to enroll in the Northern Colorado SARS-CoV-2 Biorepository (NoCo-COBIO). Blood, saliva, stool, nasopharyngeal specimens, and extensive clinical and demographic data are collected at 4 time points over 6 months. Patients are assessed for PASC during longitudinal follow-up by physician led symptom questionnaires and physical exams. This clinical trial registration is NCT04603677 . RESULTS: We have enrolled and collected samples from 119 adults since July 2020, with 66% follow-up rate. Forty-nine percent of participants assessed with a symptom surveillance questionnaire (N = 37 of 75) had PASC at any time during follow-up (up to 8 months post infection). Ninety-three percent of hospitalized participants developed PASC, while 23% of those not requiring hospitalization developed PASC. At 90-174 days post SARS-CoV-2 diagnosis, 67% of all participants had persistent symptoms (N = 37 of 55), and 85% percent of participants who required hospitalization during initial infection (N = 20) still had symptoms. The most common symptoms reported after 15 days of infection were fatigue, loss of smell, loss of taste, exercise intolerance, and cognitive dysfunction. CONCLUSIONS: Patients who were hospitalized for COVID-19 were significantly more likely to have PASC than those not requiring hospitalization, however 23% of patients who were not hospitalized also developed PASC. This patient-matched, multi-matrix, longitudinal biorepository from COVID-19 survivors with and without PASC will allow for current and future research to better understand the pathophysiology of disease and to identify targeted interventions to reduce risk for PASC. Registered 27 October 2020 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04603677 .


Asunto(s)
Bancos de Muestras Biológicas , Prueba de COVID-19/métodos , COVID-19/complicaciones , SARS-CoV-2/genética , Sobrevivientes , Adulto , Anciano , COVID-19/sangre , COVID-19/epidemiología , COVID-19/patología , COVID-19/virología , Colorado/epidemiología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Hospitalización , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Manejo de Especímenes , Adulto Joven
5.
Int J Mol Sci ; 22(13)2021 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-34199035

RESUMEN

Non-alcoholic fatty liver disease (NAFLD) is a major public health problem worldwide. NAFLD (both simple steatosis and steatohepatitis) is characterized by alterations in hepatic lipid metabolism, which may lead to the development of severe liver complications including cirrhosis and hepatocellular carcinoma. Thus, an exhaustive examination of lipid disorders in the liver of NAFLD patients is much needed. Mass spectrometry-based lipidomics platforms allow for in-depth analysis of lipid alterations in a number of human diseases, including NAFLD. This review summarizes the current research on lipid alterations associated with NAFLD and related complications, with special emphasis on the changes in long-chain and short-chain fatty acids levels in both serum and liver tissue, as well as in the hepatic expression of genes encoding the enzymes catalyzing lipid interconversions.


Asunto(s)
Susceptibilidad a Enfermedades , Ácidos Grasos/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Animales , Biomarcadores , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/metabolismo , Progresión de la Enfermedad , Ácidos Grasos/sangre , Ácidos Grasos/química , Microbioma Gastrointestinal , Regulación de la Expresión Génica , Humanos , Metabolismo de los Lípidos , Lipidómica/métodos , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/metabolismo , Estructura Molecular , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/etiología
6.
Int J Mol Sci ; 22(12)2021 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-34200784

RESUMEN

Idiopathic pulmonary fibrosis (IPF), the most lethal form of interstitial pneumonia of unknown cause, is associated with a specific radiological and histopathological pattern (the so-called "usual interstitial pneumonia" pattern) and has a median survival estimated to be between 3 and 5 years after diagnosis. However, evidence shows that IPF has different clinical phenotypes, which are characterized by a variable disease course over time. At present, the natural history of IPF is unpredictable for individual patients, although some genetic factors and circulating biomarkers have been associated with different prognoses. Since in its early stages, IPF may be asymptomatic, leading to a delayed diagnosis. Two drugs, pirfenidone and nintedanib, have been shown to modify the disease course by slowing down the decline in lung function. It is also known that 5-10% of the IPF patients may be affected by episodes of acute and often fatal decline. The acute worsening of disease is sometimes attributed to identifiable conditions, such as pneumonia or heart failure; but many of these events occur without an identifiable cause. These idiopathic acute worsenings are termed acute exacerbations of IPF. To date, clinical biomarkers, diagnostic, prognostic, and theranostic, are not well characterized. However, they could become useful tools helping facilitate diagnoses, monitoring disease progression and treatment efficacy. The aim of this review is to cover molecular mechanisms underlying IPF and research into new clinical biomarkers, to be utilized in diagnosis and prognosis, even in patients treated with antifibrotic drugs.


Asunto(s)
Biomarcadores/metabolismo , Fibrosis Pulmonar Idiopática/diagnóstico , Animales , Biomarcadores/análisis , Progresión de la Enfermedad , Humanos , Fibrosis Pulmonar Idiopática/metabolismo , Pronóstico
7.
Int J Mol Sci ; 22(12)2021 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-34200878

RESUMEN

Prostate cancer (PCa) is the most commonly diagnosed cancer in men. The diagnosis is currently based on PSA levels, which are associated with overdiagnosis and overtreatment. Moreover, most PCas are localized tumours; hence, many patients with low-/very low-risk PCa could benefit from active surveillance (AS) programs instead of more aggressive, active treatments. Heterogeneity within inclusion criteria and follow-up strategies are the main controversial issues that AS presently faces. Many biomarkers are currently under investigation in this setting; however, none has yet demonstrated enough diagnostic ability as an independent predictor of pathological or clinical progression. This work aims to review the currently available literature on tissue, blood and urine biomarkers validated in clinical practice for the management of AS patients.


Asunto(s)
Biomarcadores/análisis , Neoplasias de la Próstata/diagnóstico , Espera Vigilante/estadística & datos numéricos , Progresión de la Enfermedad , Humanos , Masculino , Neoplasias de la Próstata/prevención & control , Espera Vigilante/métodos
8.
Int J Mol Sci ; 22(13)2021 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-34202300

RESUMEN

Cancer-induced bone degradation is part of the pathological process associated with both primary bone cancers, such as osteosarcoma, and bone metastases originating from, e.g., breast, prostate, and colon carcinomas. Typically, this includes a cancer-dependent hijacking of processes also occurring during physiological bone remodeling, including osteoclast-mediated disruption of the inorganic bone component and collagenolysis. Extensive research has revealed the significance of osteoclast-mediated bone resorption throughout the course of disease for both primary and secondary bone cancer. Nevertheless, cancer cells representing both primary bone cancer and bone metastasis have also been implicated directly in bone degradation. We will present and discuss observations on the contribution of osteoclasts and cancer cells in cancer-associated bone degradation and reciprocal modulatory actions between these cells. The focus of this review is osteosarcoma, but we will also include relevant observations from studies of bone metastasis. Additionally, we propose a model for cancer-associated bone degradation that involves a collaboration between osteoclasts and cancer cells and in which both cell types may directly participate in the degradation process.


Asunto(s)
Neoplasias Óseas/patología , Neoplasias Óseas/secundario , Resorción Ósea/etiología , Resorción Ósea/metabolismo , Comunicación Celular , Osteoclastos/metabolismo , Osteosarcoma/complicaciones , Osteosarcoma/patología , Animales , Neoplasias Óseas/diagnóstico por imagen , Remodelación Ósea , Resorción Ósea/diagnóstico , Progresión de la Enfermedad , Susceptibilidad a Enfermedades , Humanos , Osteogénesis
9.
Int J Mol Sci ; 22(13)2021 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-34202537

RESUMEN

The liver is an organ with impressive regenerative potential and has been shown to heal sizable portions after their removal. However, certain diseases can overstimulate its potential to self-heal and cause excessive cellular matrix and collagen buildup. Decompensation of liver fibrosis leads to cirrhosis, a buildup of fibrotic ECM that impedes the liver's ability to efficiently exchange fluid. This review summarizes the complex immunological activities in different liver diseases, and how failure to maintain liver homeostasis leads to progressive fibrotic tissue development. We also discuss a variety of pathologies that lead to liver cirrhosis, such as alcoholic liver disease and chronic hepatitis B virus (HBV). Mesenchymal stem cells are widely studied for their potential in tissue replacement and engineering. Herein, we discuss the potential of MSCs to regulate immune response and alter the disease state. Substantial efforts have been performed in preclinical animal testing, showing promising results following inhibition of host immunity. Finally, we outline the current state of clinical trials with mesenchymal stem cells and other cellular and non-cellular therapies as they relate to the detection and treatment of liver cirrhosis.


Asunto(s)
Susceptibilidad a Enfermedades , Hepatopatías/etiología , Hepatopatías/metabolismo , Animales , Biomarcadores , Terapia Combinada , Manejo de la Enfermedad , Progresión de la Enfermedad , Susceptibilidad a Enfermedades/inmunología , Interacciones Huésped-Patógeno/genética , Interacciones Huésped-Patógeno/inmunología , Humanos , Hepatopatías/diagnóstico , Hepatopatías/terapia , Investigación en Medicina Traslacional
10.
Int J Mol Sci ; 22(13)2021 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-34202855

RESUMEN

Protein content of extracellular vesicles (EVs) can modulate different processes during carcinogenesis. Novel proteomic strategies have been applied several times to profile proteins present in exosomes released by urothelial bladder cancer (UBC) cells. However, similar studies have not been conducted so far on another population of EVs, i.e., ectosomes. In the present study we used a shotgun nanoLC-MS/MS proteomic approach to investigate the protein content of ectosomes released in vitro by T-24 UBC cells and HCV-29 normal ureter epithelial cells. In addition, cancer-promoting effects exerted by UBC-derived ectosomes on non-invasive cells in terms of cell proliferation and migratory properties were assessed. In total, 1158 proteins were identified in T-24-derived ectosomes, while HCV-29-derived ectosomes contained a lower number of 259 identified proteins. Qualitative analysis revealed 938 proteins present uniquely in T-24-derived ectosomes, suggesting their potential applications in bladder cancer management as diagnostic and prognostic biomarkers. In addition, T-24-derived ectosomes increased proliferation and motility of recipient cells, likely due to the ectosomal transfer of the identified cancer-promoting molecules. The present study provided a focused identification of biologically relevant proteins in UBC-derived ectosomes, confirming their role in UBC development and progression, and their applicability for further biomarker-oriented studies in preclinical or clinical settings.


Asunto(s)
Exosomas/metabolismo , Proteoma , Proteómica , Neoplasias de la Vejiga Urinaria/metabolismo , Biomarcadores de Tumor , Carcinoma de Células Transicionales/metabolismo , Estudios de Casos y Controles , Línea Celular Tumoral , Micropartículas Derivadas de Células/metabolismo , Cromatografía Liquida , Biología Computacional/métodos , Progresión de la Enfermedad , Vesículas Extracelulares/metabolismo , Humanos , Proteómica/métodos , Espectrometría de Masas en Tándem
11.
Sci Transl Med ; 13(600)2021 06 30.
Artículo en Inglés | MEDLINE | ID: mdl-34193611

RESUMEN

Diabetic kidney disease (DKD) and its major clinical manifestation, progressive renal decline that leads to end-stage renal disease (ESRD), are a major health burden for individuals with diabetes. The disease process that underlies progressive renal decline comprises factors that increase risk as well as factors that protect against this outcome. Using untargeted proteomic profiling of circulating proteins from individuals in two independent cohorts with type 1 and type 2 diabetes and varying stages of DKD followed for 7 to 15 years, we identified three elevated plasma proteins-fibroblast growth factor 20 (OR, 0.69; 95% CI, 0.54 to 0.88), angiopoietin-1 (OR, 0.72; 95% CI, 0.57 to 0.91), and tumor necrosis factor ligand superfamily member 12 (OR, 0.75; 95% CI, 0.59 to 0.95)-that were associated with protection against progressive renal decline and progression to ESRD. The combined effect of these three protective proteins was demonstrated by very low cumulative risk of ESRD in those who had baseline concentrations above median for all three proteins, whereas the cumulative risk of ESRD was high in those with concentrations below median for these proteins at the beginning of follow-up. This protective effect was shown to be independent from circulating inflammatory proteins and clinical covariates and was confirmed in a third cohort of diabetic individuals with normal renal function. These three protective proteins may serve as biomarkers to stratify diabetic individuals according to risk of progression to ESRD and might also be investigated as potential therapeutics to delay or prevent the onset of ESRD.


Asunto(s)
Diabetes Mellitus Tipo 2 , Fallo Renal Crónico , Biomarcadores , Progresión de la Enfermedad , Tasa de Filtración Glomerular , Humanos , Riñón/fisiología , Proteómica , Factores de Riesgo
12.
Front Immunol ; 12: 619906, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34194420

RESUMEN

The role of sMAdCAM, an important gut immune migratory marker, remains unexplored in COVID-19 pathogenesis considering recent studies positing the gut as a sanctuary site for SARS-CoV-2 persistence. Thus, assimilating profiles of systemic inflammatory mediators with sMAdCAM levels may provide insights into the progression of COVID-19 disease. Also, the role of these markers in governing virus specific immunity following infection remains largely unexplored. A cohort (n = 84) of SARS-C0V-2 infected individuals included a group of in-patients (n = 60) at various stages of disease progression together with convalescent individuals (n = 24) recruited between April and June 2020 from Mumbai, India. Follow-up of 35 in-patients at day 7 post diagnosis was carried out. Th1/Th2/Th17 cytokines along with soluble MAdCAM (sMAdCAM) levels in plasma were measured. Also, anti-viral humoral response as measured by rapid antibody test (IgG, IgM), Chemiluminescent Immunoassay (IgG), and antibodies binding to SARS-CoV-2 proteins were measured by Surface Plasmon Resonance (SPR) from plasma. IL-6 and sMAdCAM levels among in-patients inversely correlated with one another. When expressed as a novel integrated marker-sMIL index (sMAdCAM/IL-6 ratio)-these levels were incrementally and significantly higher in various disease states with convalescents exhibiting the highest values. Importantly, sMAdCAM levels as well as sMIL index (fold change) correlated with peak association response units of receptor binding domain and fold change in binding to spike respectively as measured by SPR. Our results highlight key systemic and gut homing parameters that need to be monitored and investigated further to optimally guide therapeutic and prophylactic interventions for COVID-19.


Asunto(s)
COVID-19/inmunología , Moléculas de Adhesión Celular/sangre , Interleucina-6/sangre , Mucoproteínas/sangre , Adolescente , Adulto , Anciano , Biomarcadores/sangre , COVID-19/tratamiento farmacológico , COVID-19/fisiopatología , Estudios de Cohortes , Citocinas/sangre , Progresión de la Enfermedad , Femenino , Humanos , Intestinos/inmunología , Masculino , Persona de Mediana Edad , Resonancia por Plasmón de Superficie , Adulto Joven
13.
Front Immunol ; 12: 684014, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34194438

RESUMEN

T cells play a fundamental role in the early control and clearance of many viral infections of the respiratory system. In SARS-CoV-2-infected individuals, lymphopenia with drastically reduced CD4+ and CD8+ T cells correlates with Coronavirus disease 2019 (COVID-19)-associated disease severity and mortality. In this study, we characterized cellular and humoral immune responses induced in patients with mild, severe and critical COVID-19. Peripheral blood mononuclear cells of 37 patients with mild, severe and critical COVID-19 and 10 healthy individuals were analyzed by IFNγ ELISpot and multi-color flow cytometry upon stimulation with peptide pools covering complete immunodominant SARS-CoV-2 matrix, nucleocapsid and spike proteins. In addition SARS-CoV-2 antibody levels, neutralization abilities and anaphylatoxin levels were evaluated by various commercially available ELISA platforms. Our data clearly demonstrates a significantly stronger induction of SARS-CoV-2 specific CD8+ T lymphocytes and higher IFNγ production in patients with mild compared to patients with severe or critical COVID-19. In all patients SARS-CoV-2-specific antibodies with similar neutralizing activity were detected, but highest titers of total IgGs were observed in critical patients. Finally, elevated anaphylatoxin C3a and C5a levels were identified in severe and critical COVID-19 patients probably caused by aberrant immune complex formation due to elevated antibody titers in these patients. Crucially, we provide a full picture of cellular and humoral immune responses of COVID-19 patients and prove that robust polyfunctional CD8+ T cell responses concomitant with low anaphylatoxin levels correlate with mild infections. In addition, our data indicates that high SARS-CoV-2 antibody titers are associated with severe disease progression.


Asunto(s)
Anafilatoxinas/metabolismo , Linfocitos T CD8-positivos/inmunología , COVID-19/inmunología , SARS-CoV-2/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , COVID-19/fisiopatología , Progresión de la Enfermedad , Ensayo de Immunospot Ligado a Enzimas , Femenino , Citometría de Flujo , Humanos , Inmunidad Humoral , Interferón gamma/sangre , Masculino , Persona de Mediana Edad , Gravedad del Paciente
14.
Int J Med Sci ; 18(13): 2789-2798, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34220307

RESUMEN

Coronavirus disease 2019 (COVID-19) has spread widely in the communities in many countries. Although most of the mild patients could be cured by their body's ability to self-heal, many patients quickly progressed to severe disease and had to undergo treatment in the intensive care unit (ICU). Thus, it is very important to effectively predict which patients with mild disease are more likely to progress to severe disease. A total of 72 patients hospitalized with COVID-19 in Shandong Provincial Public Health Clinical Center and 1141 patients included in the published papers were enrolled in this study. We determined that the combination of interleukin-6 (IL-6), Neutrophil (NEUT), and Natural Killer (NK) cells had the highest prediction accuracy (with 75% sensitivity and 95% specificity) for progression of COVID-19 infection. A binomial regression equation that accounted for a multiple risk score for the combination of IL-6, NEUT, and NK was also established. The multiple risk score is a good indicator for early stratification of mild patients into risk categories, which is very important for adjusting the treatment plan and preventing death.


Asunto(s)
Biomarcadores/análisis , COVID-19/etiología , Anciano , Biomarcadores/sangre , Recuento de Células Sanguíneas , COVID-19/epidemiología , Comorbilidad , Progresión de la Enfermedad , Humanos , Interleucina-6/sangre , Células Asesinas Naturales , Persona de Mediana Edad , Neutrófilos , Estudios Retrospectivos
15.
Int J Mol Sci ; 22(12)2021 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-34198582

RESUMEN

A large body of clinical and nonclinical evidence supports the role of neurotoxic soluble beta amyloid (amyloid, Aß) oligomers as upstream pathogenic drivers of Alzheimer's disease (AD). Recent late-stage trials in AD that have evaluated agents targeting distinct species of Aß provide compelling evidence that inhibition of Aß oligomer toxicity represents an effective approach to slow or stop disease progression: (1) only agents that target soluble Aß oligomers show clinical efficacy in AD patients; (2) clearance of amyloid plaque does not correlate with clinical improvements; (3) agents that predominantly target amyloid monomers or plaque failed to show clinical effects; and (4) in positive trials, efficacy is greater in carriers of the ε4 allele of apolipoprotein E (APOE4), who are known to have higher brain concentrations of Aß oligomers. These trials also show that inhibiting Aß neurotoxicity leads to a reduction in tau pathology, suggesting a pathogenic sequence of events where amyloid toxicity drives an increase in tau formation and deposition. The late-stage agents with positive clinical or biomarker data include four antibodies that engage Aß oligomers (aducanumab, lecanemab, gantenerumab, and donanemab) and ALZ-801, an oral agent that fully blocks the formation of Aß oligomers at the clinical dose.


Asunto(s)
Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/toxicidad , Progresión de la Enfermedad , Enfermedad de Alzheimer/genética , Animales , Encéfalo/patología , Humanos , Reproducibilidad de los Resultados , Solubilidad
16.
Molecules ; 26(12)2021 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-34201298

RESUMEN

The tumor microenvironment (TME) is a heterogenous assemblage of malignant and non-malignant cells, including infiltrating immune cells and other stromal cells, together with extracellular matrix and a variety of soluble factors. This complex and dynamic milieu strongly affects tumor differentiation, progression, immune evasion, and response to therapy, thus being an important therapeutic target. The phenotypic and functional features of the various cell types present in the TME are largely dependent on their ability to adopt different metabolic programs. Hence, modulating the metabolism of the cells in the TME, and their metabolic crosstalk, has emerged as a promising strategy in the context of anticancer therapies. Natural compounds offer an attractive tool in this respect as their multiple biological activities can potentially be harnessed to '(re)-educate' TME cells towards antitumoral roles. The present review discusses how natural compounds shape the metabolism of stromal cells in the TME and how this may impact tumor development and progression.


Asunto(s)
Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Microambiente Tumoral/efectos de los fármacos , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Progresión de la Enfermedad , Humanos , Neoplasias/metabolismo , Células del Estroma/efectos de los fármacos , Células del Estroma/metabolismo
17.
Int J Mol Sci ; 22(11)2021 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-34204038

RESUMEN

Metabolic syndrome (MetS) is a chronic disease, including abdominal obesity, dyslipidemia, hyperglycemia, and hypertension. It should be noted that the occurrence of MetS is closely related to oxidative stress-induced mitochondrial dysfunction, ectopic fat accumulation, and the impairment of the antioxidant system, which in turn further aggravates the intracellular oxidative imbalance and inflammatory response. As enriched anti-inflammatory and antioxidant components in plants, natural polyphenols exhibit beneficial effects, including improving liver fat accumulation and dyslipidemia, reducing blood pressure. Hence, they are expected to be useful in the prevention and management of MetS. At present, epidemiological studies indicate a negative correlation between polyphenol intake and MetS incidence. In this review, we summarized and discussed the most promising natural polyphenols (including flavonoid and non-flavonoid drugs) in the precaution and treatment of MetS, including their anti-inflammatory and antioxidant properties, as well as their regulatory functions involved in glycolipid homeostasis.


Asunto(s)
Síndrome Metabólico/tratamiento farmacológico , Polifenoles/uso terapéutico , Sustancias Protectoras/uso terapéutico , Animales , Ensayos Clínicos como Asunto , Progresión de la Enfermedad , Humanos , Polifenoles/química , Polifenoles/farmacología , Sustancias Protectoras/farmacología , Transducción de Señal/efectos de los fármacos
18.
Int J Mol Sci ; 22(11)2021 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-34204103

RESUMEN

Research on the neurobiology of cancer, which lies at the border of neuroscience and oncology, has elucidated the mechanisms and pathways that enable the nervous system to modulate processes associated with cancer initiation and progression. This research has also shown that several drugs which modulate interactions between the nervous system and the tumor micro- and macroenvironments significantly reduced the progression of cancer in animal models. Encouraging results were also provided by prospective clinical trials investigating the effect of drugs that reduce adrenergic signaling on the course of cancer in oncological patients. Moreover, it has been shown that reducing adrenergic signaling might also reduce the incidence of cancer in animal models, as well as in humans. However, even if many experimental and clinical findings have confirmed the preventive and therapeutic potential of drugs that reduce the stimulatory effect of the nervous system on processes related to cancer initiation and progression, several questions remain unanswered. Therefore, the aim of this review is to critically evaluate the efficiency of these drugs and to discuss questions that need to be answered before their introduction into conventional cancer treatment and prevention.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/prevención & control , Animales , Antineoplásicos/farmacología , Encéfalo/efectos de los fármacos , Encéfalo/patología , Progresión de la Enfermedad , Humanos , Microbiota/efectos de los fármacos , Neoplasias/patología , Transducción de Señal/efectos de los fármacos
19.
Int J Mol Sci ; 22(12)2021 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-34204767

RESUMEN

Increased airway wall thickness and remodeling of bronchial mucosa are characteristic of asthma and may arise from altered integrin signaling on airway cells. Here, we analyzed the expression of ß1-subfamily integrins on blood and airway cells (flow cytometry), inflammatory biomarkers in serum and bronchoalveolar lavage, reticular basement membrane (RBM) thickness and collagen deposits in the mucosa (histology), and airway geometry (CT-imaging) in 92 asthma patients (persistent airflow limitation subtype: n = 47) and 36 controls. Persistent airflow limitation was associated with type-2 inflammation, elevated soluble α2 integrin chain, and changes in the bronchial wall geometry. Both subtypes of asthma showed thicker RBM than control, but collagen deposition and epithelial α1 and α2 integrins staining were similar. Type-I collagen accumulation and RBM thickness were inversely related to the epithelial expression of the α2 integrin chain. Expression of α2ß1 integrin on T-cells and eosinophils was not altered in asthma. Collagen I deposits were, however, more abundant in patients with lower α2ß1 integrin on blood and airway CD8+ T-cells. Thicker airway walls in CT were associated with lower α2 integrin chain on blood CD4+ T-cells and airway eosinophils. Our data suggest that α2ß1 integrin on inflammatory and epithelial cells may protect against airway remodeling advancement in asthma.


Asunto(s)
Asma/metabolismo , Asma/patología , Progresión de la Enfermedad , Integrina alfa2beta1/metabolismo , Pulmón/patología , Sustancias Protectoras/metabolismo , Adulto , Anciano , Remodelación de las Vías Aéreas (Respiratorias) , Asma/sangre , Asma/inmunología , Membrana Basal/patología , Bronquios/diagnóstico por imagen , Bronquios/patología , Bronquios/fisiopatología , Lavado Broncoalveolar , Femenino , Humanos , Inflamación/patología , Pulmón/diagnóstico por imagen , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Membrana Mucosa/patología , Subunidades de Proteína/metabolismo , Ventilación Pulmonar , Solubilidad , Linfocitos T/metabolismo , Tomografía Computarizada por Rayos X
20.
Molecules ; 26(12)2021 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-34200914

RESUMEN

Flavonoids are a group of secondary metabolites derived from plant-based foods, and they offer many health benefits in different stages of several diseases. This review will focus on their effects on ion channels expressed in vascular smooth muscle during atherosclerosis. Since ion channels can be regulated by redox potential, it is expected that during the onset of oxidative stress-related diseases, ion channels present changes in their conductive activity, impacting the progression of the disease. A typical oxidative stress-related condition is atherosclerosis, which involves the dysfunction of vascular smooth muscle. We aim to present the state of the art on how redox potential affects vascular smooth muscle ion channel function and summarize if the benefits observed in this disease by using flavonoids involve restoring the ion channel activity.


Asunto(s)
Aterosclerosis/tratamiento farmacológico , Flavonoides/farmacología , Músculo Liso Vascular/efectos de los fármacos , Animales , Aterosclerosis/metabolismo , Progresión de la Enfermedad , Humanos , Canales Iónicos/metabolismo , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Oxidación-Reducción/efectos de los fármacos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...