RESUMO
There are nearly 65 million people with chronic heart failure (CHF) globally, with no treatment directed at the pathologic cause of the disease, the loss of functioning cardiomyocytes. We have an allogeneic cardiac patch comprised of cardiomyocytes and human fibroblasts on a bioresorbable matrix. This patch increases blood flow to the damaged heart and improves left ventricular (LV) function in an immune competent rat model of ischemic CHF. After 6 months of treatment in an immune competent Yucatan mini swine ischemic CHF model, this patch restores LV contractility without constrictive physiology, partially reversing maladaptive LV and right ventricular remodeling, increases exercise tolerance, without inducing any cardiac arrhythmias or a change in myocardial oxygen consumption. Digital spatial profiling in mice with patch placement 3 weeks after a myocardial infarction shows that the patch induces a CD45pos immune cell response that results in an infiltration of dendritic cells and macrophages with high expression of macrophages polarization to the anti-inflammatory reparative M2 phenotype. Leveraging the host native immune system allows for the potential use of immunomodulatory therapies for treatment of chronic inflammatory diseases not limited to ischemic CHF.
Assuntos
Insuficiência Cardíaca , Infarto do Miocárdio , Ratos , Camundongos , Humanos , Animais , Suínos , Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Insuficiência Cardíaca/metabolismo , Miócitos Cardíacos/metabolismo , Função Ventricular Esquerda , Macrófagos/metabolismoRESUMO
Several studies have demonstrated that the serum of patients with cancer contains antibodies that react with a group of autoantigens denominated tumor-associated antigens (TAA). TAA can be detected prior to clinical diagnosis; thus, they would be ideal biomarkers for early detection of cancer, using only a few microliters of a patient's serum. In the current study, we used an immune proteomic approach, combining two-dimensional (2D) electrophoresis, Western blot, and matrix-associated laser desorption/ionization-mass spectrometry (MALDI-MS) methods to identify TAA in the sera of patients diagnosed with breast cancer. Sera were obtained from 36 newly diagnosed patients with stage II breast cancer and those from 36 healthy volunteers were evaluated for the presence of the TAA. Alpha 2HS-glycoprotein (AHSG) antibodies were detected in 33 of 36 patients with breast cancer (91.7%) and in only 3 of 36 healthy patients (controls, 8.3%). Sensitivity of detection of autoantibodies against AHSG in patients with breast cancer was 91.7%. AHSG was detected in cancer tissue by immunohistochemistry. Our results strongly suggest that the presence of serum autoantibodies against AHSG protein may be useful as serum biomarkers for early-stage breast cancer screening and minimally invasive diagnosis in Mexican populations. BIOLOGICAL SIGNIFICANCE: In the present study, 2D immunoblot analysis was used to make a screening in samples of sera from patients with a diagnosis of early-stage breast cancer, in order to identify some autoantibodies that react against TAA. Proteins identified in the present study, particularly alpha 2HS-glycoprotein (AHSG), might be useful as potential biomarkers for breast cancer in early stages for Mexican populations.
Assuntos
Anticorpos Antineoplásicos/sangue , Antígenos de Neoplasias/sangue , Autoanticorpos/sangue , Neoplasias da Mama/sangue , alfa-2-Glicoproteína-HS/metabolismo , Biomarcadores Tumorais/sangue , Feminino , Humanos , México , Estadiamento de Neoplasias , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodosRESUMO
Birth weight is considered as the most important indicator of growth and intrauterine development as well as the nutritional status of the newborn. Several reports have demonstrated the influence of both biological and social variables on low birth weight, among which being discussed is the influence of the mothers work activities. Two hundred and thirty-two newborns were studied at the Regional Hospital "20 de Noviembre" of the Institute de Seguridad y Servicios Sociales para los Trabajadores del Estado (ISSSTE) and selected based on inclusion and exclusion criteria which homogenized the sample and allowed to associate the work status of the mother with the low birth weight of the child. The somatometric data of the newborns was obtained from official registrars from the Perinatology Ward and directly from the mothers who were interviewed. The results did not significant statistical differences in the weight of the newborns of those mothers who do work than in those who don't. It was concluded that for this sample, the favorable socioeconomic fund established by a double family income apparently compensates any disadvantages which the work activity could have on the newborns' weight.