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Malignant ventricular arrhythmia (VA) after myocardial infarction (MI) is mainly caused by myocardial electrophysiological remodeling. Brahma-related gene 1 (BRG1) is an ATPase catalytic subunit that belongs to a family of chromatin remodeling complexes called Switch/Sucrose Non-Fermentable Chromatin (SWI/SNF). BRG1 has been reported as a molecular chaperone, interacting with various transcription factors or proteins to regulate transcription in cardiac diseases. In this study, we investigated the potential role of BRG1 in ion channel remodeling and VA after ischemic infarction. Myocardial infarction (MI) mice were established by ligating the left anterior descending (LAD) coronary artery, and electrocardiogram (ECG) was monitored. Epicardial conduction of MI mouse heart was characterized in Langendorff-perfused hearts using epicardial optical voltage mapping. Patch-clamping analysis was conducted in single ventricular cardiomyocytes isolated from the mice. We showed that BRG1 expression in the border zone was progressively increased in the first week following MI. Cardiac-specific deletion of BRG1 by tail vein injection of AAV9-BRG1-shRNA significantly ameliorated susceptibility to electrical-induced VA and shortened QTc intervals in MI mice. BRG1 knockdown significantly enhanced conduction velocity (CV) and reversed the prolonged action potential duration in MI mouse heart. Moreover, BRG1 knockdown improved the decreased densities of Na+ current (INa) and transient outward potassium current (Ito), as well as the expression of Nav1.5 and Kv4.3 in the border zone of MI mouse hearts and in hypoxia-treated neonatal mouse ventricular cardiomyocytes. We revealed that MI increased the binding among BRG1, T-cell factor 4 (TCF4) and ß-catenin, forming a transcription complex, which suppressed the transcription activity of SCN5A and KCND3, thereby influencing the incidence of VA post-MI.
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Infarto del Miocardio , Ratones , Animales , Infarto del Miocardio/metabolismo , Arritmias Cardíacas/genética , Miocardio/patología , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Miocitos Cardíacos/metabolismoRESUMEN
The concept of resilience can be realized in natural and engineering systems, representing the ability of a system to adapt and recover from various disturbances. Although resilience is a critical property needed for understanding and managing the risks and collapses of transportation systems, an accepted and useful definition of resilience for urban traffic as well as its statistical property under perturbations are still missing. Here, we define city traffic resilience based on the spatiotemporal clusters of congestion in real traffic and find that the resilience follows a scale-free distribution in 2D city road networks and 1D highways with different exponents but similar exponents on different days and in different cities. The traffic resilience is also revealed to have a scaling relation between the cluster size of the spatiotemporal jam and its recovery duration independent of microscopic details. Our findings of universal traffic resilience can provide an indication toward better understanding and designing of these complex engineering systems under internal and external disturbances.
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Systemic air embolism is a rare but potentially fatal complication related to many factors. The purpose of this article is to alert clinicians once patients occurs an abnormal neurological and cardiovascular status, following minor traumatic treatment, air embolism should be considered. A 20-year-old man who presented with fungal pneumonia with lung cavities formation was admitted to an intensive care unit (ICU) and received positive airway pressure ventilation. Four days later, the fungal pneumonia was improved, but the patient's blood pressure and arterial oxygen saturation deteriorated, so computed tomography (CT) scans were preformed to reevaluate him. The scans detected air embolism in the left atrium and ventricle, ascending aorta, aortic arch and its branches (right brachiocephalic, bilateral common carotid and right subclavian arteries), descending aorta and right coronary artery. A CT scan of the abdomen revealed air in the spleen, cauda pancreatic, superior mesenteric artery and right external iliac artery. The patient died two days later from multiple organ dysfunction. We suggest that vascular air embolism should be considered under mechanical ventilation when patients' neurologic and cardiovascular status deteriorates, and hyperbaric oxygen therapy should be conducted immediately.
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Embolia Aérea/etiología , Enfermedades Pulmonares Fúngicas/complicaciones , Respiración con Presión Positiva/efectos adversos , Adulto , Embolia Aérea/diagnóstico por imagen , Embolia Aérea/terapia , Resultado Fatal , Humanos , Oxigenoterapia Hiperbárica , Pulmón/diagnóstico por imagen , Pulmón/patología , Enfermedades Pulmonares Fúngicas/diagnóstico por imagen , Enfermedades Pulmonares Fúngicas/patología , Enfermedades Pulmonares Fúngicas/terapia , Masculino , Insuficiencia Multiorgánica/etiología , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
A marine bacterial strain, F72T, was isolated from a solitary scleractinian coral, collected in Yap seamounts in the Pacific Ocean. Strain F72T is a Gram-negative, light-yellow-pigmented, motile, rod-shaped bacterium. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain F72T is related to the genus Novosphingobium and has high 16S rRNA gene sequence similarities with the type strains of Novosphingobium pentaromativorans US6-1T (97.7 %), Novosphingobium panipatense SM16T (97.6 %), Novosphingobium mathurense SM117T (97.2 %) and Novosphingobium barchaimii LL02T (97.1 %). Ubiquinone Q-10 was detected as the dominant quinone. The predominant cellular fatty acids were C18:1ω7c and C17:1ω6c. The genomic DNA G+C content of strain F72T was 63.4 mol %. The polar lipids profile contained phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine, phosphatidylcholine, sphingoglycolipid and one uncharacterized lipid. Strain F72T shared DNA relatedness of 25 % with N. pentaromativorans JCM 12182T, 31 % with N. panipatense DSM 22890T, 21 % with N. mathurense DSM 23374T and 26 % with N. barchaimii DSM 25411T. Combined data from phenotypic, phylogenetic and DNA-DNA relatedness studies demonstrated that the strain F72T is a representative of a novel species of the genus Novosphingobium, for which we propose the name Novosphingobium profundi sp. nov. (type strain F72T = KACC 18566T = CGMCC 1.15390T).
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Antozoos/microbiología , Agua de Mar/microbiología , Sphingomonadaceae/aislamiento & purificación , Animales , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/metabolismo , Ácidos Grasos/química , Ácidos Grasos/metabolismo , Océano Pacífico , Filogenia , ARN Ribosómico 16S/genética , Sphingomonadaceae/clasificación , Sphingomonadaceae/genética , Sphingomonadaceae/metabolismoRESUMEN
A Gram-stain-negative, rod-shaped, yellow-pigmented, gliding bacterial strain, designated S5-23-3T, was isolated from a sediment sample of the Yellow Sea in China. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain S5-23-3T was related to the genus Winogradskyella and had highest 16S rRNA gene sequence similarities with Winogradskyella arenosi JCM 15527T (97.6 %), Winogradskyella rapida CECT 7392T (97.4 %) and Winogradskyella undariae KCTC 32261T (97.2 %). The predominant cellular fatty acids were iso-C15 : 0, iso-C15 : 1 G, iso-C15 : 0 3-OH and iso-C17 : 0 3-OH. Strain S5-23-3T contained MK-6 as the predominant menaquinone. The polar lipid profile contained phosphatidylethanolamine, two aminolipids, one aminoglycolipid, one aminophospholipid, one unidentified phospholipid and seven unidentified polar lipids. The genomic DNA G+C content of strain S5-23-3T was 36.1 mol%. Combined data from phenotypic, chemotaxonomic, phylogenetic and DNA-DNA relatedness studies demonstrated that strain S5-23-3T is a representative of a novel species of the genus Winogradskyella, for which the name Winogradskyellasediminis sp. nov. (type strain S5-23-3T=LMG 28075T=DSM 28134T) is proposed.
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Flavobacteriaceae/clasificación , Sedimentos Geológicos/microbiología , Filogenia , Agua de Mar/microbiología , Técnicas de Tipificación Bacteriana , Composición de Base , China , ADN Bacteriano/genética , Ácidos Grasos/química , Flavobacteriaceae/genética , Flavobacteriaceae/aislamiento & purificación , Hibridación de Ácido Nucleico , Fosfolípidos/química , Pigmentación , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMEN
A Gram-stain-negative, rod-shaped bacterial strain, designated S9-10T, was isolated from a sediment sample from the Yellow Sea near China. Phylogenetic analysis of 16S rRNA gene sequences revealed that strain S9-10T was a member of the family Flavobacteriaceaeand formed a distinct lineage. The genomic DNA G+C content of strain S9-10T was 34.2 mol%. The major respiratory quinone was MK-6. The predominant cellular fatty acids were iso-C15 : 0 (21.1 %), iso-C15 : 1G (16.3 %) and iso-C17 : 0 3-OH (12.0 %). The polar lipid profile contained phosphatidylethanolamine, aminophospholipid, aminoglycolipid, two unidentified aminolipids and five unidentified polar lipids. On the basis of phenotypic, genotypic, chemotaxonomic and phylogenetic analyses, strain S9-10T represents a novel species of a novel genus of the family Flavobacteriaceae, for which the name Oceanihabitans sediminis gen. nov., sp. nov. is proposed. The type strain of Oceanihabitans sediminis is S9-10T (=DSM 28133T =LMG 28074T).
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Flavobacteriaceae/clasificación , Filogenia , Agua de Mar/microbiología , Técnicas de Tipificación Bacteriana , Composición de Base , China , ADN Bacteriano/genética , Ácidos Grasos/química , Flavobacteriaceae/genética , Flavobacteriaceae/aislamiento & purificación , Fosfolípidos/química , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMEN
A Gram-stain-negative, rod-shaped, strictly aerobic, motile bacterial strain, designated TP162T, was isolated from a seamount near the Yap Trench in the tropical western Pacific. Phylogenetic analysis based on 16S rRNA gene sequence showed that strain TP162T was related to the genus Pseudoalteromonas and had highest 16S rRNA gene sequence similarities with the type strains Pseudoalteromonas shioyasakiensis SE3T (98.2 %), Pseudoalteromonas lipolytica LMEB 39T (97.7 %), Pseudoalteromonas arabiensis k53T (97.4 %) and Pseudoalteromonas aliena KMM 3562T (97.2 %). The predominant cellular fatty acids were summed feature 3 (composed of iso-C15 : 0 2-OH and/or C16 : 1ω7c), C17 : 1ω8c and C16 : 0. The quinone system for strain TP162T comprised predominantly ubiquinone-8, and the polar lipid profile contained phosphatidylethanolamine, phosphatidylglycerol, one unidentified phospholipid and four unidentified lipids. The genomic DNA G+C content of strain TP162T was 46.7 mol%. Strain TP162T shared 28 % DNA-DNA relatedness with P.shioyasakiensis JCM 18891T, 21 % with P. lipolytica JCM 15903T, 35 % with P.arabiensis JCM 17292T and 18 % with P.aliena LMG 22059T. Combined data from phenotypic, chemotaxonomic, phylogenetic and DNA-DNA relatedness studies demonstrated that strain TP162T is a representative of a novel species of the genus Pseudoalteromonas, for which we propose the name Pseudoalteromonas profundi sp. nov. (type strain TP162T=KACC 18554T=CGMCC 1.15394T).
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Filogenia , Pseudoalteromonas/clasificación , Agua de Mar/microbiología , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Océano Pacífico , Fosfolípidos/química , Pseudoalteromonas/genética , Pseudoalteromonas/aislamiento & purificación , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Ubiquinona/químicaRESUMEN
Heavy traffic jams are difficult to predict due to the complexity of traffic dynamics. Understanding the network dynamics of traffic bottlenecks can help avoid critical large traffic jams and improve overall traffic conditions. Here, we develop a method to forecast heavy congestions based on their early propagation stage. Our framework follows the network propagation and dissipation of the traffic jams originated from a bottleneck emergence, growth, and its recovery and disappearance. Based on large-scale urban traffic-speed data, we find that dissipation duration of jams follows approximately power-law distributions, and typically, traffic jams dissolve nearly twice slower than their growth. Importantly, we find that the growth speed, even at the first 15 minutes of a jam, is highly correlated with the maximal size of the jam. Our methodology can be applied in urban traffic control systems to forecast heavy traffic bottlenecks and prevent them before they propagate to large network congestions.
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Background: PFI-3 is a small-molecule inhibitor that targets the bromodomains (BRDs) of Brahma-related gene 1 (BRG1). This monomeric compound, which has high selectivity and potent cellular effects, has recently been developed. Although PFI-3 has been reported as a potential therapeutic agent targeting thrombomodulin, its role in the regulation of vascular function remains unknown. Therefore, we aimed to investigate the impact of PFI-3 on arterial vessel tone. Methods: A microvascular tension measurement device (DMT) was utilized to identify alterations in vascular tension within the mesenteric artery. To detect variations in cytosolic [Ca2+]i, a Fluo-3/AM fluorescent probe and fluorescence microscope were employed. Additionally, whole-cell patch clamp techniques were utilized to evaluate the activity of L-type voltage-dependent calcium channels (VDCCs) in cultured arterial smooth muscle cells (A10 cells). Results: PFI-3 exerted a dose-dependent relaxation effect on rat mesenteric arteries with both intact and denuded endothelium after phenylephrine (PE)- and high-K+-induced constriction. PFI-3-induced vasorelaxation was not affected by the presence of L-NAME/ODQ or K+ channel blockers (Gli/TEA). PFI-3 abolished Ca2+-induced contraction on endothelium-denuded mesenteric arteries preincubated by PE in Ca2+-free solution. Incubation with TG had no impact on PFI-3-induced vasorelaxation pre-contracted by PE. PFI-3 reduced Ca2+-induced contraction on endothelium-denuded mesenteric arteries pre-incubated by KCl (60 mM) in Ca2+-free solution. PFI-3 declined extracellular calcium influx in A10 cells detected by Fluo-3/AM fluorescent probe and fluorescence microscope. Furthermore, we observed that PFI-3 decreased the current densities of L-type VDCC by whole-cell patch clamp techniques. Conclusions: PFI-3 blunted PE and high K+-induced vasoconstriction independent of endothelium on rat mesenteric artery. The vasodilatory effect of PFI-3 may be attributed to its inhibition of VDCCs and receptor-operated calcium channels (ROCCs) on vascular smooth muscle cells (VSMCs).
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Calcio , Colorantes Fluorescentes , Animales , Ratas , Calcio/metabolismo , Canales de Calcio Tipo L/farmacología , Colorantes Fluorescentes/farmacología , Arterias MesentéricasRESUMEN
BACKGROUND: Recently, nonalcoholic fatty liver disease (NAFLD) has been renamed metabolic-associated fatty liver disease (MAFLD). Based on the definition for MAFLD, a group of non-obese and metabolically healthy individuals with fatty liver are excluded from the newly proposed nomenclature. AIM: To analyze the histologic features in the MAFLD and non-MAFLD subgroups of NAFLD. METHODS: Eighty-three patients with biopsy-proven NAFLD were separated into MAFLD and non-MAFLD groups. The diagnosis of MAFLD was established as hepatic steatosis along with obesity/diabetes or evidence of metabolic dysfunction. The histologic features were compared according to different metabolic disorders and liver enzyme levels. RESULTS: MAFLD individuals had a higher NAFLD activity score (P = 0.002) and higher severity of hepatic steatosis (42.6% Grade 1, 42.6% Grade 2, and 14.8% Grade 3 in MAFLD; 81.8% Grade 1, 13.6% Grade 2, and 4.5% Grade 3 in non-MAFLD; P = 0.007) than the non-MAFLD group. Lobular and portal inflammation, hepatic ballooning, fibrosis grade, and the presence of nonalcoholic steatohepatitis (NASH) and significant fibrosis were comparable between the two groups. The higher the liver enzyme levels, the more severe the grades of hepatic steatosis (75.0% Grade 1 and 25.0% Grade 2 in normal liver function; 56.6% Grade 1, 39.6% Grade 2, and 3.8% Grade 3 in increased liver enzyme levels; 27.8% Grade 1, 27.8% Grade 2, and 44.4% Grade 3 in liver injury; P < 0.001). Patients with liver injury (alanine aminotransferase > 3 × upper limit of normal) presented a higher severity of hepatocellular ballooning (P = 0.021). Moreover, the grade of steatosis correlated significantly with hepatocellular ballooning degree (r = 0.338, P = 0.002) and the presence of NASH (r = 0.466, P < 0.001). CONCLUSION: Metabolic dysfunction is associated with hepatic steatosis but no other histologic features in NAFLD. Further research is needed to assess the dynamic histologic characteristics in NAFLD based on the presence or absence of metabolic disorders.
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The objective of this study was to evaluate the fertilization capability of White Bengal Tiger frozen-thawed completely immotile spermatozoa after interspecific intracytoplasmic sperm injection (ICSI) with bovine oocytes. The fertilization status of presumptive zygotes was assessed 18 h after ICSI by immunofluorescence staining and confocal microscopy. The fertilization rate was 34.8% (8/23), as confirmed by the extrusion of two polar bodies, or male and female pronuclei formation. For unfertilized oocytes (65.2%, 15/23), one activated oocyte had an activated spermatozoon but most were unactivated oocytes with unactivated spermatozoa (1/15, 6.7% vs 10/15, 66.7%, respectively, p < 0.05). These results showed that White Bengal Tiger frozen-thawed completely immotile spermatozoa retained the capacity to fertilize bovine oocytes after interspecific ICSI. This is the first report of in vitro produced zygotes using tiger immotile sperm with bovine oocytes by interspecific ICSI technique, which provides an efficient and feasible method for preservation and utilization of endangered feline animals.
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Fabrication of metal nanoparticle (NP)-based strain sensors with both a broad working range and linearity range is still a significant challenge. Typically, homogeneous conductive percolation networks are indispensable for linear sensing performance, whereas inhomogeneous microstructures may inevitably arise under large strain due to the formation of defects in rigid NPs. In this study, a sandwich-structured strain sensor with an extraordinarily large stretchability (800%) yet self-healing property is fabricated by three-dimensional printing using a liquid metal-like Ag NP ink. The strain sensor shows an initial conductivity of 248 S cm-1, a good linearity in two strain ranges, and a long-term stability after undergoing 5000 cycles under a strain level of 100%. Such highly comprehensive sensing performance is attributed to the unique structure of the Ag NP ink, in which Ag NPs coalesce together after room-temperature sintering triggered by chlorides, and then, the sintered Ag aggregates tend to form continuous conductive networks through hydrogen bonds between polyacrylic acid and carboxymethylcellulose. Further, the free flow of Ag aggregates is the root cause that leads to the change of relative resistance as demonstrated by finite element simulation. This Ag NP-based strain sensor shows high potential for application in monitoring human knuckle motion.
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BACKGROUND: Primary bone lymphoma (PBL) is an uncommon extranodal disease that represents approximately 1%-3% of lymphomas. Anaplastic lymphoma kinase (ALK) positive anaplastic large-cell lymphoma (ALCL) is an extremely rare type of PBL. The aim of this report is describe the symptoms, diagnosis, and treatment of primary bone ALK-positive ALCL. CASE SUMMARY: A 66-year-old man presented to our hospital with neck and shoulder pain and intermittent fever that lasted for 1 mo. After extensive evaluation, positron emission tomography-computed tomography (CT) examination showed multiple osteolytic bone lesions without other sites lesions. CT-guided biopsy of the T10 vertebral body was performed, and the pathology results showed that neoplastic cells were positive for ALK-1, CD30, and CD3. A diagnosis of primary bone ALK positive ALCL was ultimately made. The patient was in partial response after four cycle soft cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy, and we planned to repeat the biopsy and radiological examination after completion of the fifth cycle of therapy. CONCLUSION: Primary bone ALK positive ALCL is a rare disease and physicians should keep in mind that ALCL can present with isolated osseous involvement without nodal involvement, and lymphoma should be considered in the differential diagnosis of primary bone lesions.
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ABSTRACT: Early determination of coronavirus disease 2019 (COVID-19) pneumonia from numerous suspected cases is critical for the early isolation and treatment of patients.The purpose of the study was to develop and validate a rapid screening model to predict early COVID-19 pneumonia from suspected cases using a random forest algorithm in China.A total of 914 initially suspected COVID-19 pneumonia in multiple centers were prospectively included. The computer-assisted embedding method was used to screen the variables. The random forest algorithm was adopted to build a rapid screening model based on the training set. The screening model was evaluated by the confusion matrix and receiver operating characteristic (ROC) analysis in the validation.The rapid screening model was set up based on 4 epidemiological features, 3 clinical manifestations, decreased white blood cell count and lymphocytes, and imaging changes on chest X-ray or computed tomography. The area under the ROC curve was 0.956, and the model had a sensitivity of 83.82% and a specificity of 89.57%. The confusion matrix revealed that the prospective screening model had an accuracy of 87.0% for predicting early COVID-19 pneumonia.Here, we developed and validated a rapid screening model that could predict early COVID-19 pneumonia with high sensitivity and specificity. The use of this model to screen for COVID-19 pneumonia have epidemiological and clinical significance.
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Algoritmos , Prueba de COVID-19/métodos , COVID-19/diagnóstico , Tamizaje Masivo/métodos , SARS-CoV-2/aislamiento & purificación , Adulto , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Curva ROC , Sensibilidad y EspecificidadRESUMEN
Novel coronavirus pneumonia (NCP) has been widely spread in China and several other countries. Early finding of this pneumonia from huge numbers of suspects gives clinicians a big challenge. The aim of the study was to develop a rapid screening model for early predicting NCP in a Zhejiang population, as well as its utility in other areas. A total of 880 participants who were initially suspected of NCP from January 17 to February 19 were included. Potential predictors were selected via stepwise logistic regression analysis. The model was established based on epidemiological features, clinical manifestations, white blood cell count, and pulmonary imaging changes, with the area under receiver operating characteristic (AUROC) curve of 0.920. At a cut-off value of 1.0, the model could determine NCP with a sensitivity of 85% and a specificity of 82.3%. We further developed a simplified model by combining the geographical regions and rounding the coefficients, with the AUROC of 0.909, as well as a model without epidemiological factors with the AUROC of 0.859. The study demonstrated that the screening model was a helpful and cost-effective tool for early predicting NCP and had great clinical significance given the high activity of NCP.
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COVID-19/diagnóstico , COVID-19/epidemiología , Tamizaje Masivo , Modelos Biológicos , Neumonía/diagnóstico , SARS-CoV-2/fisiología , Adulto , China/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROCRESUMEN
ES (embryonic stem)-derived cells have been investigated in many animal models of severe injury and degenerative disease. However, few studies have examined the ability of ES-derived cells to improve functional outcome following partially damaged breast and also the modification of mammary tissue to produce costly proteins. This study investigates the feasibility of implanting mES-dK (mouse ES-derived keratinocytes-like) cells stably transfected with a mammary gland special expression vector for the PBD-1 (porcine beta-defensin 1) in developing mammary glands. Our aim was to assess the ability of cell grafting to improve functional outcome following partial damage of the breast, also on the breast modification mammary tissue in mice for the production of PBD-1 protein secreted in the milk. Our results showed that the ratios of the surviving cells labelled with the myoepithelial or luminal cell markers, EMA (epithelial membrane antigen) and CALLA, were 41.7 +/- 15.2% and 28.4 +/- 9.6%, respectively, which revealed that transplanted mES-dK cells survived, integrated in vivo and differentiated into myoepithelial or luminal cells. In addition, Western blot analysis showed that 37.5% (3 out of 8) female transplanted mice had PBD-1 expression in their milk and reached 0.4998, 0.5229 and 0.5195 microg/ml, respectively.
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Células Madre Embrionarias/citología , Expresión Génica , Queratinocitos/metabolismo , Queratinocitos/trasplante , Glándulas Mamarias Animales/metabolismo , Leche/metabolismo , beta-Defensinas/genética , beta-Defensinas/metabolismo , Animales , Reactores Biológicos , Western Blotting , Diferenciación Celular , Linaje de la Célula , Células Cultivadas , Femenino , Vectores Genéticos , Queratinocitos/citología , Lactancia , Ratones , Ratones Transgénicos , Mucina-1/análisis , Neprilisina/análisis , Reacción en Cadena de la Polimerasa , Proteínas Recombinantes/metabolismo , Porcinos/genética , TransfecciónRESUMEN
BACKGROUND: Augmenter of liver regeneration (ALR) is an important polypeptide in the process of liver regeneration. This study aimed to determine the expression level of ALR in different liver diseases and its significance. METHODS: We prepared murine polyclonal antibody against ALR protein from Balb/C mice and purified the IgG fraction, which specifically combined to ALR protein as shown by Western blotting. Serum ALR levels in patients with hepatocellular carcinoma (HCC), hepatic failure (HF), chronic hepatitis B, and healthy persons were compared by ELISA. ALR mRNA expression levels in liver tissues in some of these patients were also compared by real-time RT-PCR. Immunohistochemical analysis was carried out on HF and HCC liver tissues. RESULTS: Different serum ALR levels foreshowed completely different prognoses in 18 HF patients. Higher ALR levels were noted in 6 improved patients (1613.5+/-369.6 pmol/ml) than in 12 deteriorating patients (462.3+/-235.8 pmol/ml). Similar levels were found in 20 HCC patients (917.9+/-332.7 pmol/ml), 24 chronic hepatitis B patients (969.2+/-332.5 pmol/ml) and 10 healthy persons (806.9+/-240.8 pmol/ml). ALR mRNA levels in HCC liver tissues [10E6.24 (1.74X10(6)) copies/µl] were much higher than in those of HF patients receiving orthotopic liver transplantation [10E3.45 (2.82X10(3)) copies/µl] or in healthy liver tissues [10E4.31 (2.04X10(4)) copies/µl]. In immunohistochemical analysis, positive immunostaining in HCC liver tissue was more intense than that in HF liver tissue. CONCLUSION: Serum ALR level is helpful in estimating the survival time of patients with HF, and ALR may play an important role in hepatocarcinogenesis.
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Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/metabolismo , Fallo Hepático/diagnóstico , Fallo Hepático/metabolismo , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/metabolismo , Proteínas/metabolismo , ARN Mensajero/metabolismo , Western Blotting , Carcinoma Hepatocelular/genética , Enfermedad Crónica , Ensayo de Inmunoadsorción Enzimática , Hepatitis B/metabolismo , Humanos , Neoplasias Hepáticas/genética , Regeneración Hepática , Pronóstico , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
OBJECTIVE: To investigate the expression and role of augmenter of liver regeneration (ALR) in hepatic failure. METHODS: ALR polyclonal antibody was prepared and purified. Serum ALR in patients with hepatic failure, chronic hepatitis B and healthy persons were quantified by ELISA, ALR mRNA in hepatic tissues were quantified by real-time PCR. RESULTS: Different serum ALR levels foreshowed different outcomes for hepatic failure patients: The liver function was restored in 6 patients with higher ALR level [(1613.5+/-369.6) pmol/ml], and the liver function was deteriorated in 12 patients with lower ALR level [(462.3+/-235.8) pmol/ml]. ALR level in patients with chronic hepatitis B [(969.2+/-332.5) pmol/ml] was similar to that in healthy persons [(806.9+/-240.8) pmol/ml]. ALR mRNA level in hepatic failure patients receiving OLT (103.45 copies/microl) was lower than that in chronic hepatitis B patients (104.37 copies/microl) and healthy persons (104.31 copies/microl), ALR mRNA level in chronic hepatitis B and healthy persons was similar. CONCLUSION: These findings suggest serum ALR level reflected ALR mRNA level in liver and is helpful in estimating the survival time of patients with hepatic failure.
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Hepatitis B Crónica/metabolismo , Fallo Hepático Agudo/metabolismo , Hígado/metabolismo , Proteínas/metabolismo , Animales , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Femenino , Expresión Génica , Hepatitis B Crónica/sangre , Hepatitis B Crónica/patología , Hepatocitos/metabolismo , Humanos , Hígado/patología , Fallo Hepático Agudo/sangre , Fallo Hepático Agudo/patología , Regeneración Hepática , Ratones , Ratones Endogámicos BALB C , Reacción en Cadena de la Polimerasa/métodos , Pronóstico , Proteínas/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismoRESUMEN
Chronic hepatitis B (CHB) is a major global health burden. Liver fibrosis, an insidious process, is the main histopathological change in CHB that might lead to the end-stage liver disease if left untreated. The intermediate liver fibrosis (S2) is the optimal time to start antiviral therapy. The aim of the present study was to examine the proteomic changes in patients with CHB at different fibrotic stages, with a view to identify future serum biomarkers for S2. Ninety CHB patients were grouped into mild (S0-1), intermediate (S2), and severe liver fibrosis (S3-4) (61 men and 29 women; age 25-63 years). Isobaric tagging for relative and absolute quantitation was applied to screen proteins differentially expressed among the patient groups. Another 46 patients with CHB (age 25-59 years; 31 men and 15 women), and 16 healthy controls (age 26-61 years; 11 men and 5 women) were enrolled in a validation group. Enzyme-linked immunosorbent assay was used to verify the diagnostic value of the candidate biomarkers. We found 139 proteins that were differentially expressed between various fibrotic stage-paired comparisons. Five protein candidates were selected as potential biomarkers of S2 for further verification. Notably, ficolin-2 (FCN2) and carboxypeptidase B2 (CPB2) showed differential expression between patients and healthy controls. In conclusion, serum proteomic changes reported here offer new molecular leads for future research on biomarker candidates to identify liver fibrotic stages in CHB. In particular, FCN2 and CPB2 warrant further research on their possible mechanistic involvement in CHB pathogenesis.
Asunto(s)
Biomarcadores/sangre , Hepatitis B Crónica/sangre , Cirrosis Hepática/sangre , Proteómica/métodos , Adulto , Carboxipeptidasa B2/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Lectinas/sangre , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , FicolinasRESUMEN
Atherosclerosis (AS) is a chronic inflammatory disease characterized by accumulating deposition of lipids in the arterial intima. Notably, macrophages participate centrally in the pathogenesis of this deadly disease. In this study, we established AS mouse models in order to investigate the effect of microRNA-133b (miR-133b) on vulnerable plaque formation and vascular remodeling in AS and explore the potential functional mechanisms. The expression of miR-133b was altered or the Notch-signaling pathway was blocked in the AS mouse models in order to evaluate the proliferation, migration, and apoptosis of macrophages. It was observed that miR-133b was upregulated in AS, which might target MAML1 to regulate the Notch-signaling pathway. AS mice with downregulated miR-133b or inhibited Notch-signaling pathway presented with a reduced AS plaque area, a decreased positive rate of macrophages, and an increased positive rate of vascular smooth muscle cells. Moreover, Notch-signaling pathway blockade or miR-133b downregulation inhibited the macrophage viability and migration and accelerated the apoptosis. This study provides evidence that downregulated miR-133b expression may inhibit the immune responses of macrophages and attenuate the vulnerable plaque formation and vascular remodeling in AS mice through the MAML1-mediated Notch-signaling pathway, highlighting miR-133b as a novel therapeutic target for AS.