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An outbreak of coronavirus disease 2019 (COVID-19) has spread globally, with over 500 million cases and 6 million deaths to date. COVID-19 is associated with a systemic inflammatory response and abnormalities of the extracellular matrix (ECM), which is also involved in inflammatory storms. Upon viral infection, ECM proteins are involved in the recruitment of inflammatory cells and interference with target organ metabolism, including in the lungs. Additionally, serum biomarkers of ECM turnover are associated with the severity of COVID-19 and may serve as potential targets. Consequently, understanding the expression and function of ECM, particularly of the lung, during severe acute respiratory syndrome of the coronavirus 2 infection would provide valuable insights into the mechanisms of COVID-19 progression. In this review, we summarize the current findings on ECM, such as hyaluronic acid, matrix metalloproteinases, and collagen, which are linked to the severity and inflammation of COVID-19. Some drugs targeting the extracellular surface have been effective. In the future, these ECM findings could provide novel perspectives on the pathogenesis and treatment of COVID-19.
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BACKGROUND: Pneumonia caused by the 2019 novel Coronavirus (COVID-2019) shares overlapping signs and symptoms, laboratory findings, imaging features with influenza A pneumonia. We aimed to identify their clinical characteristics to help early diagnosis. METHODS: We retrospectively retrieved data for laboratory-confirmed patients admitted with COVID-19-induced or influenza A-induced pneumonia from electronic medical records in Ningbo First Hospital, China. We recorded patients' epidemiological and clinical features, as well as radiologic and laboratory findings. RESULTS: The median age of influenza A cohort was higher and it exhibited higher temperature and higher proportion of pleural effusion. COVID-19 cohort exhibited higher proportions of fatigue, diarrhea and ground-glass opacity and higher levels of lymphocyte percentage, absolute lymphocyte count, red-cell count, hemoglobin and albumin and presented lower levels of monocytes, c-reactive protein, aspartate aminotransferase, alkaline phosphatase, serum creatinine. Multivariate logistic regression analyses showed that fatigue, ground-glass opacity, and higher level of albumin were independent risk factors for COVID-19 pneumonia, while older age, higher temperature, and higher level of monocyte count were independent risk factors for influenza A pneumonia. CONCLUSIONS: In terms of COVID-19 pneumonia and influenza A pneumonia, fatigue, ground-glass opacity, and higher level of albumin tend to be helpful for diagnosis of COVID-19 pneumonia, while older age, higher temperature, and higher level of monocyte count tend to be helpful for the diagnosis of influenza A pneumonia.
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COVID-19/diagnóstico , COVID-19/virología , Técnicas de Laboratorio Clínico , Virus de la Influenza A/fisiología , Neumonía/diagnóstico , Neumonía/virología , SARS-CoV-2/fisiología , COVID-19/diagnóstico por imagen , Diagnóstico Diferencial , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neumonía/diagnóstico por imagen , Factores de Riesgo , Tomografía Computarizada por Rayos XRESUMEN
Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and chronic airway inflammation, caused by a combination of environmental and genetic factors. It is the third leading cause of death worldwide. In recent years, researchers have applied the genome-wide association study (GWAS) and identified a large number of genetic variants associated with lung functions and potential drug targets for treating COPD. In this review, we summarize the results of GWAS studies and perform a review of the literature since 2007 to highlight the progress of GWAS on COPD. We discuss the challenges, the underlying mechanisms, and the possible drug targets, thereby providing insights on the pathogenesis and potential treatment strategies for COPD.
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Estudio de Asociación del Genoma Completo , Enfermedad Pulmonar Obstructiva Crónica , Predisposición Genética a la Enfermedad , Humanos , Pulmón , Polimorfismo de Nucleótido SimpleRESUMEN
Since the outbreak of coronavirus disease 2019 (COVID-19) in December 2019, an epidemic has spread rapidly worldwide. COVID-19 is caused by the highly infectious severe acute respiratory syndrome coronavirus-2. A 42-year-old woman presented to hospital who was suffering from epigastric discomfort and dyspepsia for the past 5 days. Before the onset of symptoms, she was healthy, and had no travel history to Wuhan or contact with laboratory-confirmed COVID-19 cases. An examination showed chronic superficial gastritis with erosion and esophagitis. Enhanced magnetic resonance imaging of the abdomen showed a lesion in the right lower lobe of the lungs. Chest computed tomography showed multiple ground-glass opacity in the lungs. Reverse transcription-polymerase chain reaction was negative for severe acute respiratory syndrome coronavirus-2. There was no improvement after antibiotic treatment. Polymerase chain reaction performed 2 days later was positive and she was diagnosed with COVID-19. After several days of antiviral and symptomatic treatments, her symptoms improved and she was discharged. None of the medical staff were infected. Clinical manifestations of COVID-19 are nonspecific, making differentiating it from other diseases difficult. This case shows the sequence in which symptoms developed in a patient with COVID-19 with gastrointestinal symptoms as initial manifestations.
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Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/complicaciones , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/virología , Neumonía Viral/complicaciones , Adulto , COVID-19 , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Femenino , Enfermedades Gastrointestinales/patología , Humanos , Pandemias , Neumonía Viral/transmisión , Neumonía Viral/virología , Pronóstico , SARS-CoV-2Asunto(s)
Betacoronavirus/fisiología , Infecciones por Coronavirus/virología , Neumonía Viral/virología , COVID-19 , Prueba de COVID-19 , China/epidemiología , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Alta del Paciente , Neumonía Viral/epidemiología , SARS-CoV-2 , Esparcimiento de VirusRESUMEN
Nephronectin (NPNT) is a novel extracellular matrix protein and a new ligand of integrin α8ß1. Recent studies showed that NPNT is highly expressed in kidney, lung, thyroid, etc, and it may play an important role in many pathological conditions. NPNT is involved in the process of kidney development and acute kidney injury, regulates proliferation and differentiation of osteoblast, and induces the vasculogenesis in vitro. NPNT may play a key role in pathological osteoporosis and therefore be a new therapeutic target of bone diseases. NPNT gene variants are not only associated with lung function, but also potentially implicated in chronic airway diseases development. Moreover, NPNT is also an important factor that mediates pathology of cardiac, epidermis, breast, liver and teeth diseases. In this paper, we reviewed some research progresses on the structure, distribution, physiological and pathophysiological functions of NPNT.
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Proteínas de la Matriz Extracelular/fisiología , Riñón/fisiología , Osteoblastos/citología , Diferenciación Celular , Proliferación Celular , Humanos , OsteoporosisRESUMEN
OBJECTIVE: To study the effect and mechanism of chimonin on pulmonary arterioles I and III type collagen metabolism in pulmonary hypertension rats induced by chronic hypoxic hypercapnia. METHODS: Thirty-six Sprague-Dawley rats were randomly divided into three groups: normal control group(A), hypoxic hypercapnic group(B), hypoxic hypercapnia + chimonin group(C). Collagen I, III and their mRNA, Blood CO concentration (COHb%), activity of HO-1 in blood serum and lung homogenate, content of hydroxyproline in lung homogenate, pulmonary arteriole micromorphometric index were observed. RESULTS: Hypoxic hypercapnic rats's mPAP, Hyr of lung homogenate, content of I type collagen and I type collagen mRNA in pulmonary arterioles, were significantly higher than those in control group, pulmonary vessel remodeling of hypoxic hypercapnic rats was significant, those changes in hypercapnia + chimonin group were significantly lower than those in hypoxic hypercapnic group. Blood CO concentration, activity of HO-1 in blood serum and lung homogenate in rats of hypoxic hypercapnic rats were significantly higher than those of control group, and those of hypercapnia + chimonin group were even higher than hypoxic hypercapnic group (P < 0.01). There was no significant difference in mCAP, content of III type collagen and their mRNA in three groups (P > 0.05). CONCLUSION: Chimonin can reduce pulmonary hypertension and pulmonary vessel remodeling induced by hypoxic hypercapnia through inhibiting proliferation of collagen I, the mechanism maybe is up regulating endogenous carbon monoxide system.
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Colágeno Tipo I/metabolismo , Medicamentos Herbarios Chinos/farmacología , Hipertensión Pulmonar/fisiopatología , Hipoxia/fisiopatología , Pulmón/irrigación sanguínea , Animales , Arteriolas/metabolismo , Monóxido de Carbono/metabolismo , Enfermedad Crónica , Colágeno Tipo III/metabolismo , Hipercapnia/complicaciones , Hipercapnia/fisiopatología , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/metabolismo , Hipoxia/complicaciones , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: Set up a method to isolate and identify the small pulmonary arterial smooth muscle cells (PASMCs) in vitro. METHODS: In sterile conditions, separated the male SD rat pulmonary artery, digested by collagenase I and cultured primary PASMCs. Measured cell viability; observed by phase contrast microscope; identified by immunocytochemistry and immunofluorescence staining as a label for smooth muscle alpha-actin. RESULTS: PASMCs were identified by morphology and immunocytochemistry, immunofluorescence staining, with the cell viability is over 96.5%. The primary culture could be subcultured after 4-7 days and successfully passaged without change in morphology and growth characteristic. CONCLUSION: This technique has advantage of the method is simple, short cultivate, good reproducibility, the primary cultured PASMCs quantity and the rapid growth.
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Músculo Liso Vascular/citología , Miocitos del Músculo Liso/citología , Cultivo Primario de Células/métodos , Arteria Pulmonar/citología , Animales , Arteriolas/citología , Separación Celular/métodos , Pulmón/irrigación sanguínea , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by suppressing apoptosis and enhancing cell proliferation in the vascular wall. Inducing pulmonary artery smooth muscle cells (PASMC) apoptosis had been regarded as a therapeutic approach for PAH. Oridonin can cause apoptosis in many cell lines, while little has been done to evaluate its effect on PASMC. METHODS: Thirty male Sprague-Dawley rats were randomly assigned to three groups: normal control (NC); hypoxia-hypercapnia (HH); Hypoxia-hypercapnia + oridonin (HHO). Rats were exposed to hypoxia-hypercapnia for four weeks. Cultured human PASMC (HPASMC) were assigned to three groups: normoxia (NO); hypoxia (HY); hypoxia + oridonin (HO). The mean pulmonary artery pressure, mass ratio of right ventricle over left ventricle plus septum (RV/(LV + S)), the ratio of thickness of the pulmonary arteriole wall to vascular external diameter (WT%) and the ratio of the vessel wall area to the total area (WA%) were measured. Morphologic changes of pulmonary arteries were observed under light and electron microscopes. The apoptotic characteristics in vitro and in vivo were detected. RESULTS: The mPAP, RV/(LV + S), WT%, and WA% in the HH group were significantly greater than those in the NC (P < 0.01) and HHO groups (P < 0.01); the activities of caspase-3 and caspase-9, and the expressions of Bax, cyt-C and apoptotic index (AI) in the group HH were less than those in the NC and HHO groups; and the expression of Bcl-2 in group HH was greater than that in the NC and HHO groups. HPASMC mitochondrial membrane potentials in group HO was lower than in group HY (P < 0.01), and cyt-C in the cytoplasm, AI, and caspase-9 in the HO group were greater than that in the HY group (P < 0.01), but the expression of Bcl-2 in the HO group was less than that in the HY group (P < 0.05). CONCLUSIONS: The results suggest that oridonin can lower pulmonary artery pressure effectively, and inhibit pulmonary artery structural remodeling by inducing smooth cell apoptosis via a mitochondria-dependent pathway.