RESUMEN
Objective: To investigate the pathological characteristics and the clinical significance of novel coronavirus (2019-nCoV)-infected pneumonia (termed by WHO as coronavirus disease 2019, COVID-19). Methods: Minimally invasive autopsies from lung, heart, kidney, spleen, bone marrow, liver, pancreas, stomach, intestine, thyroid and skin were performed on three patients died of novel coronavirus pneumonia in Chongqing, China. Hematoxylin and eosin staining (HE), transmission electron microcopy, and histochemical staining were performed to investigate the pathological changes of indicated organs or tissues. Immunohistochemical staining was conducted to evaluate the infiltration of immune cells as well as the expression of 2019-nCoV proteins. Real time PCR was carried out to detect the RNA of 2019-nCoV. Results: Various damages were observed in the alveolar structure, with minor serous exudation and fibrin exudation. Hyaline membrane formation was observed in some alveoli. The infiltrated immune cells in alveoli were majorly macrophages and monocytes. Moderate multinucleated giant cells, minimal lymphocytes, eosinophils and neutrophils were also observed. Most of infiltrated lymphocytes were CD4-positive T cells. Significant proliferation of type â ¡ alveolar epithelia and focal desquamation of alveolar epithelia were also indicated. The blood vessels of alveolar septum were congested, edematous and widened, with modest infiltration of monocytes and lymphocytes. Hyaline thrombi were found in a minority of microvessels. Focal hemorrhage in lung tissue, organization of exudates in some alveolar cavities, and pulmonary interstitial fibrosis were observed. Part of the bronchial epithelia were exfoliated. Coronavirus particles in bronchial mucosal epithelia and type â ¡ alveolar epithelia were observed under electron microscope. Immunohistochemical staining showed that part of the alveolar epithelia and macrophages were positive for 2019-nCoV antigen. Real time PCR analyses identified positive signals for 2019-nCoV nucleic acid. Decreased numbers of lymphocyte, cell degeneration and necrosis were observed in spleen. Furthermore, degeneration and necrosis of parenchymal cells, formation of hyaline thrombus in small vessels, and pathological changes of chronic diseases were observed in other organs and tissues, while no evidence of coronavirus infection was observed in these organs. Conclusions: The lungs from novel coronavirus pneumonia patients manifest significant pathological lesions, including the alveolar exudative inflammation and interstitial inflammation, alveolar epithelium proliferation and hyaline membrane formation. While the 2019-nCoV is mainly distributed in lung, the infection also involves in the damages of heart, vessels, liver, kidney and other organs. Further studies are warranted to investigate the mechanism underlying pathological changes of this disease.
Asunto(s)
Infecciones por Coronavirus , Pulmón/patología , Pandemias , Neumonía Viral , Autopsia , Betacoronavirus/genética , Betacoronavirus/aislamiento & purificación , COVID-19 , China , Infecciones por Coronavirus/patología , Humanos , Riñón/patología , Hígado/patología , Miocardio/patología , Neumonía Viral/patología , Reacción en Cadena en Tiempo Real de la Polimerasa , SARS-CoV-2 , Piel/patología , Glándula Tiroides/patologíaRESUMEN
Fluorescence imaging signal is severely limited by the quantum efficiency and emission wavelength. To overcome these challenges, novel NIR-emitting K5NdLi2F10 nanoparticles under NIR excitation was introduced as fluorescence imaging probe for the first time. The photostability of K5NdLi2F10 nanoparticles in the water, phosphate buffer saline, fetal bovine serum and living mice was investigated. The fluorescence signal was detected with depths of 3.5 and 2.0 cm in phantom and pork tissue, respectively. Fluorescence spectrum with a significant signal-to-background ratio of 10:1 was captured in living mice. Moreover, clear NIR images were virtualized for the living mice after intravenous injection. The imaging ability of nanoparticles in tumor-beard mice were evaluated, the enrichment of K5NdLi2F10 nanoparticles in tumor site due to the enhanced permeability and retention effect was confirmed. The systematic studies of toxicity, bio-distribution and in-vivo dynamic imaging suggest that these materials give high biocompatibility and low toxicity. These NIR-emitting nanoparticles with high quantum efficiency, high penetration and low toxicity might facilitate tumor identification in deep tissues more sensitively.
Asunto(s)
Diagnóstico por Imagen/métodos , Rayos Infrarrojos , Nanoestructuras/química , Teoría Cuántica , Animales , Supervivencia Celular , Eritrocitos/citología , Femenino , Células HeLa , Hemólisis , Humanos , Ratones Endogámicos BALB C , Ratones Desnudos , Nanoestructuras/toxicidad , Nanoestructuras/ultraestructura , Imagen Óptica , Especificidad de Órganos , Fantasmas de Imagen , Ratas Sprague-Dawley , Espectrometría de Fluorescencia , PorcinosRESUMEN
This case-control study aimed to investigate the association between PHLDB1 rs498872 polymorphism and the risk of glioma in a Chinese Han population. A total of 210 patients and 235 controls were enrolled in this study. The CT genotype and TT genotype were significantly associated with the risk of glioma (OR=1.48, 95%CI 1.00-2.19, P=0.05 and OR=2.40, 95%CI 1.06-4.10, P=0.03), respectively. In addition, T allele of PHLDB1 rs498872 polymorphism was significantly associated with an increased risk of glioma (OR=1.58, 95%CI 1.08-2.29, P=0.02). We also found that PHLDB1 rs498872 polymorphism was not associated with histology and tumor grade of glioma. In conclusion, this study found that PHLDB1 rs498872 polymorphism was significantly associated with glioma risk in Chinese Han population.
Asunto(s)
Neoplasias Encefálicas/genética , Predisposición Genética a la Enfermedad , Glioma/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas del Tejido Nervioso/genética , Polimorfismo de Nucleótido Simple , Adulto , Alelos , Pueblo Asiatico , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/etnología , Neoplasias Encefálicas/patología , Estudios de Casos y Controles , Femenino , Expresión Génica , Frecuencia de los Genes , Glioma/diagnóstico , Glioma/etnología , Glioma/patología , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Oportunidad Relativa , Factores de RiesgoRESUMEN
Abnormal proliferation of vascular smooth muscle cells (VSMCs) is known to be a key event in the development of atherosclerosis and restenosis. The present study examined the effect of a novel synthetic natriuretic peptide, vasonatrin peptide (VNP), on norepinephrine (NE)-induced proliferation of VSMCs from coronary bypass vessels. Human VSMCs were isolated from an internal mammary artery (IMA) and saphenous vein (SV) by explant culture and stimulated with NE. MTT assay and [3H] thymidine-incorporation were undertaken to analyze cell proliferation and radioimmunoassay was used to determine the level of intracellular cyclic 3',5'-guanosine monophosphate (cyclic GMP). NE (10(-8) - 10(-7) mol/l) had a mitogenic effect in human VSMCs from both SV and IMA. However, NE-stimulated proliferation of VSMCs from SV was greater than that from IMA. Furthermore, low concentration of NE (10(-10) mol/l) promoted cell growth in SV-derived cells but not in IMA-derived cells. VNP (10(-8) - 10(-6) mol/l) reduced NE-induced cell proliferation and increased intracellular cyclic GMP, which were abrogated by HS-142-1. In addition, the growth inhibition of VNP was mimicked by 8-bromo-cGMP. These results indicate that VNP has a significant inhibitory effect on NE-stimulated proliferation of human VSMCs from both IMA and SV, which is mediated by guanylate cyclase-linked receptors by increasing cyclic GMP.
Asunto(s)
Factor Natriurético Atrial/farmacología , Proliferación Celular/efectos de los fármacos , Puente de Arteria Coronaria , Arterias Mamarias/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Vena Safena/efectos de los fármacos , Análisis de Varianza , Células Cultivadas , Relación Dosis-Respuesta a Droga , Inhibidores de Crecimiento/farmacología , Humanos , Arterias Mamarias/citología , Músculo Liso Vascular/citología , Vena Safena/citologíaRESUMEN
The purpose of this work was to test the hypothesis that vasonatrin peptide (VNP) can attenuate the growth-promoting effect by hypoxia in cardiac fibroblasts of cultured neonatal rats. Cultured fibroblasts were divided into four groups: control group, hypoxia group, VNP group and VNP+hypoxia group. The growth of cardiac fibroblasts was observed using MTT method and the incorporation of (3)H-TdR, and the effect of VNP on the intracellular level of Ca(2+) was measured by means of interactive laser cytometry. It was found that hypoxia (2% - 3%) increased significantly the MTT optical density (OD) of cardiac fibroblasts (P<0.05 vs control group), but the increase was greatly attenuated in the VNP (10(- 6)mol/L) group and also the incorporation of (3)H-TdR in cardiac fibroblasts (P<0.05 vs hypoxia group). VNP (10(- 6)mol/L) also decreased the intracellular level of Ca(2+) which was increased by hypoxia (P<0.05) as compared with control and hypoxia group. These findings demonstrate that VNP can attenuate the hypoxia-induced growth-promoting effect in cardiac fibroblasts, which may be associated with the elevation of intracellular Ca(2+).
Asunto(s)
Factor Natriurético Atrial/farmacología , Calcio/metabolismo , Fibroblastos/metabolismo , Miocardio/citología , Animales , Animales Recién Nacidos , Hipoxia de la Célula , Células Cultivadas , Depresión Química , Fibroblastos/citología , Miocardio/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
The host response to gram-negative endotoxin is characterized by an influx of inflammatory cells into host tissues, mediated in part by localized production of chemokines. In this study, using subtractive suppression hybridization analysis, we demonstrate that ANA-1 murine macrophages produce the CC chemokine, MIP-1gamma, in response to LPS-mediated NO production. Gene transcription and protein translation are upregulated in the setting of LPS-induced NO synthesis. However, NO alone is a necessary but insufficient cofactor for induction of MIP-1gamma protein expression; an NO-independent LPS signalling pathway is also required. This study suggests a novel mechanism by which NO modulates the host inflammatory response to endotoxin.
Asunto(s)
Regulación de la Expresión Génica/efectos de los fármacos , Lipopolisacáridos/farmacología , Proteínas Inflamatorias de Macrófagos/genética , Macrófagos/efectos de los fármacos , Óxido Nítrico/farmacología , Animales , Antropología Cultural , Quimiocina CCL4 , Relación Dosis-Respuesta a Droga , Inflamación/genética , Macrófagos/fisiología , Ratones , Transcripción Genética/efectos de los fármacosRESUMEN
In this paper, the mutagenicity and carcinogenicity of alternariol monomethyl ether (AME), alternariol (AOH), and their relevance to the etiology of human esophageal cancer were studied. These mycotoxins were produced by Alternaria alternata which was the main contaminating fungi isolated from the grain in Linxian County, an area with high incidence of esophageal cancer. This study demonstrated that: 1. AME and AOH might cause cell mutagenicity and transformation; 2. AME and AOH could combine with the DNA isolated from human fetal esophageal epithelium, activate the oncogens, c-H-ras and c-mys in it, and promote proliferation of human fetal esophageal epithelium in vitro; 3. squamous cell carcinoma of the fetal esophagus could be induced by AOH. According to the results of the studies of AME and AOH mentioned above, we consider that Alternaria alternata plays an important role in the etiology of human esophageal cancer.