RESUMO
Both anti-glomerular basement membrane (GBM) disease and the anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are common causes of pulmonary-renal syndrome. Organizing pneumonia (OP), a special pattern of interstitial lung disease, is extremely rare either in AAV or anti-GBM disease. We report an old woman presented with OP on a background of co-presentation with both ANCA and anti-GBM antibodies.
Assuntos
Doença Antimembrana Basal Glomerular , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Glomerulonefrite , Pneumonia em Organização , Pneumonia , Feminino , Humanos , Anticorpos Anticitoplasma de Neutrófilos , Autoanticorpos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicaçõesRESUMO
Hyperbranched polysaccharides (HBPSs) are the main components in cell wall and exopolysaccharide (EPS) of Pleurotus tuber-regium. To enhance the yield of these macromolecules, corn oil at 4% addition exhibited the best effect for production of mycelial biomass at 20.49 g/L and EPS at 0.59 g/L, which was 2.56 folds and 1.90 folds of the control, respectively. The treated hyphae were much thicker with smooth surface, while its cell wall content (43.81 ± 0.02%) was 1.96 times of the control (22.34 ± 0.01%). Moreover, a large number of lipid droplets could be visualized under the view of confocal laser scanning microscopy (CLSM). RNA-seq analysis revealed that corn oil could enter the cells and result in the up-regulation of genes on cell morphology and membrane permeability, as well as the down-regulation on expression level of polysaccharide hydrolase and genes involved in the MAPK pathway, all of which probably contribute to the increase of polysaccharides production.
Assuntos
Óleo de Milho , Pleurotus , Biomassa , Micélio/metabolismo , Pleurotus/metabolismo , Polissacarídeos/metabolismoRESUMO
Aggregated metastatic cancer cells, referred to as circulating tumor cell (CTC) clusters, are present in the blood of cancer patients and contribute to cancer metastasis. However, the origin of CTC clusters, especially intravascular aggregates, remains unknown. Here, we employ suspension culture methods to mimic CTC cluster formation in the circulation of breast cancer patients. CTC clusters generated using these methods exhibited an increased metastatic potential that was defined by the overexpression of heparanase (HPSE). Heparanase induced FAK- and ICAM-1-dependent cell adhesion, which promoted intravascular cell aggregation. Moreover, knockdown of heparanase or inhibition of its activity with JG6, a heparanase inhibitor, was sufficient to block the formation of cell clusters and suppress breast cancer metastasis. Our data reveal that heparanase-mediated cell adhesion is critical for metastasis mediated by intravascular CTC clusters. We also suggest that targeting the function of heparanase in cancer cell dissemination might limit metastatic progression.
Assuntos
Neoplasias da Mama/fisiopatologia , Agregação Celular/fisiologia , Glucuronidase/fisiologia , Metástase Neoplásica/fisiopatologia , Células Neoplásicas Circulantes/metabolismo , Animais , Adesão Celular/fisiologia , Linhagem Celular Tumoral , Feminino , Quinase 1 de Adesão Focal/metabolismo , Glucuronidase/genética , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Camundongos Endogâmicos BALB C , Paxilina/metabolismo , Regulação para Cima , Quinases da Família src/metabolismoRESUMO
Wu-tou Decoction (WTD) is a classic herbal formula in traditional Chinese medicine for the treatment of joint diseases, neuropathic pain (NP) and inflammatory pain. In this study we investigated whether WTD produced analgesic action in a mouse spinal nerve ligation (SNL) model and elucidated the underlying molecular mechanisms. Mice were subjected to SNL and orally treated with WTD (3.15, 6.30 or 12.60 g·kg-1·d-1) for 21 d. SNL induced mechanical hyperalgesia and heat hyperalgesia characterized by rapid and persistent pain hypersensitivity. In addition, the expression levels of IL-1ß, TNF-α, CCL2 and CXCL1 in the spinal cord dorsal horn were dramatically increased on the 10th d post-surgery. Oral administration of WTD dose-dependently suppressed both mechanical and heat hyperalgesia as well as the expression levels of inflammatory cytokines in the spinal cord dorsal horn on the 21st d post-surgery. Then whole-genome microarray analyses were conducted to detect the gene expression profiles of spinal cord dorsal horn in SNL mice with or without WTD treatment. After construction of the WTD-SNL-network and topological analysis, a list of candidate target genes of WTD acting on SNL-induced NP was identified and found to be functionally enriched in several glial cell activation-related pathways and neuroinflammatory pathways. Our data have clarified the gene expression patterns in the mouse spinal cord under the NP condition. We also demonstrate the analgesic action of WTD through suppression of glial cell activation and neuroinflammation, which suggest the potential of WTD as a promising candidate for the treatment of NP.
Assuntos
Analgésicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Perfilação da Expressão Gênica/métodos , Medicina Tradicional Chinesa/métodos , Neuralgia/tratamento farmacológico , Análise de Sequência com Séries de Oligonucleotídeos , Corno Dorsal da Medula Espinal/efeitos dos fármacos , Biologia de Sistemas/métodos , Administração Oral , Analgésicos/administração & dosagem , Animais , Comportamento Animal/efeitos dos fármacos , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/administração & dosagem , Regulação da Expressão Gênica , Redes Reguladoras de Genes/efeitos dos fármacos , Masculino , Camundongos Endogâmicos ICR , Neuralgia/genética , Neuralgia/metabolismo , Neuralgia/fisiopatologia , Limiar da Dor/efeitos dos fármacos , Células do Corno Posterior/efeitos dos fármacos , Células do Corno Posterior/metabolismo , Transdução de Sinais/efeitos dos fármacos , Corno Dorsal da Medula Espinal/metabolismo , Corno Dorsal da Medula Espinal/fisiopatologia , Fatores de Tempo , TranscriptomaRESUMO
The pleiotropic pro-inflammatory cytokine, macrophage migration inhibitory factor (MIF), represents an important link between chronic inflammation and tumorigenesis. Although accumulating evidence demonstrates that MIF overexpression is implicated in the development and progression of multiple cancers, including esophageal squamous cell carcinoma (ESCC), the molecular mechanisms underlying its tumor-promoting roles in ESCC remain unclear. In the present study, we observed that MIF is overexpressed in ESCC and correlated significantly with lymph node metastasis, advanced clinical stage, and poor survival of ESCC. MIF knockdown attenuated the proliferation, migration, and invasion of ESCC cells in vitro and in vivo. Moreover, blockage of MIF expression decreased the activation of the Akt, MEK/ERK, and NF-κB pathways and enhanced sensitivity to apoptosis. Meanwhile, repression of MIF expression resulted in activation of glycogen synthase kinase 3 beta (GSK3ß) and subsequent decrease of active ß-catenin, as well as its downstream targets including cyclin D1, matrix metalloproteinase (MMP)-7, c-myc, and c-Jun. Collectively, our results provided mechanistic insights into the tumor-promoting role of MIF in ESCC, and suggested that MIF represents a potential therapeutic target for treatment of ESCC.
Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Glicogênio Sintase Quinase 3 beta/fisiologia , Fatores Inibidores da Migração de Macrófagos/fisiologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Adulto , Idoso , Animais , Apoptose , Carcinoma de Células Escamosas/mortalidade , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Fatores Inibidores da Migração de Macrófagos/análise , Masculino , Camundongos , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de NeoplasiasRESUMO
BACKGROUND: The axon initial segment (AIS) is a specialized membrane region in the axon of neurons wherein numerous specific voltage-gated sodium channels (VGSCs) are clustered and action potentials are initiated. The AIS is currently considered as a new plastic hotspot. METHODS: We investigated the alterations in Nav1.6 (SCN8A) and its adapter protein ankyrin G in the AIS of the hippocampal cornu ammonis 3 (CA3) pyramidal cells of rat after status epilepticus induced by lithium-pilocarpine (PISE). RESULTS: Nav1.6 and ankyrin G were colocalized in the AIS of hippocampal CA3 pyramidal neurons. Compared with the control group, the protein and mRNA expression of Nav1.6 increased within 24 h and 60 days after PISE. By contrast, ankyrin G protein expression decreased slightly within 24 h but increased within 60 days, whereas ankyrin G mRNA increased within 24 h and 60 days after PISE. However, the protein and mRNA expression levels of Nav1.6 and ankyrin G within 7 days after PISE did not differ significantly with those of the control. CONCLUSIONS: Nav1.6 and ankyrin G may participate in the plastic changes in the AIS of hippocampus CA3 neurons after PISE and play potential roles in epileptogenesis by regulating neuronal excitability.
Assuntos
Axônios/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Compostos de Lítio/toxicidade , Plasticidade Neuronal/efeitos dos fármacos , Pilocarpina/toxicidade , Estado Epiléptico/fisiopatologia , Potenciais de Ação/fisiologia , Animais , Hipocampo/fisiopatologia , Masculino , Ratos , Ratos Sprague-Dawley , Estado Epiléptico/induzido quimicamenteRESUMO
The treatment of Alzheimer's disease (AD) has been hampered by a lack of sensitive and specific non-invasive diagnostic methods. Quantum dots (QD) are nano-crystals with unique photo-physical properties that bypass some of the limitations of conventional dyes and imaging tools. This study is aimed to evaluate the fluorescence properties of a QD probe conjugated with an anti-Aß antibody (QD-Aß-Ab). Healthy mice and mice bearing mutated human APP695swe and APP717 V-F transgenes received intracerebroventricular injection of the probe for subsequent imaging. Immunohistochemistry revealed that Aß1-42 was distributed in the hippocampus CA1 area in the APP transgenic mice. Fluorescence microscopy demonstrated that fluorescence was mainly observed in the hippocampus area, the cerebral cortex, sagittal septum and striatum of APP transgenic mice. In vivo imaging of mice receiving the QD-Aß-Ab probe showed that healthy mice exhibited a narrow range of fluorescence and lower fluorescence intensity compared with APP transgenic mice. The mean fluorescence intensity of brain tissues of healthy C57BL mice was 12.3784 ± 3.9826, which was significantly lower than that of 10- and 16-month-old APP transgenic mice (45.03 ± 2.66 and 46.69 ± 3.22, respectively; P < 0.05). In this study we present the first direct evidence that QD-Aß-Ab conjugate probes can track in vivo state of Aß accumulation in mice and the findings suggest that such probes may be of potential use for early molecular diagnostic imaging of AD.
Assuntos
Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/imunologia , Anticorpos/metabolismo , Imagem Molecular/métodos , Pontos Quânticos/metabolismo , Doença de Alzheimer/patologia , Animais , Região CA1 Hipocampal/metabolismo , Região CA1 Hipocampal/patologia , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microscopia de Fluorescência , Pontos Quânticos/toxicidadeRESUMO
BACKGROUND: The expression pattern and function of miRNAs in the rat model of temporal lobe epilepsy have not been well defined. Profiling miRNA expression in the rat model of temporal lobe epilepsy and investigating the function of specific miRNAs in epilepsy offers the prospect of a deeper understanding of the mechanisms of epilepsy. METHODS: The lithium-pilocarpine-induced status epilepticus model and the temporal lobe epilepsy model were established in Sprague-Dawley rats. Samples were analysed to detect deregulated miRNAs in the hippocampal temporal lobe, and several of these deregulated miRNAs were confirmed by qPCR. The expression of the pro-apoptotic miR-34a was detected at 1 day, 7 days and 2 weeks post-status epilepticus and at 2 months after temporal lobe epilepsy. The antagomir of miR-34a was then utilised. The expression of miR-34a after targeting and the expression change of activated caspase-3 protein were examined. The effects of altering the expression of miR-34a and activated caspase-3 protein on neuronal survival and neuronal death or apoptosis post-status epilepticus were assessed. RESULTS: The miRNA microarray detected 9 up-regulated miRNAs (miR-146a, -211, -203, -210, -152, -31, -23a, -34a, -27a) and 15 down-regulated miRNAs (miR-138*, -301a, -136, -153, -19a, -135b, -325-5p, -380, -190, -542-3p, -33, -144, -542-5p, -543, -296*). Some of the deregulated miRNAs (miR-146a, miR-210, miR-27a, miR-135b and miR-33) were confirmed using qPCR. Furthermore, an increase in expression of the pro-apoptotic miR-34a was demonstrated in the post-status epilepticus rat hippocampus. miR-34a was significantly up-regulated at 1 day, 7 days and 2 weeks post-status epilepticus and at 2 months after temporal lobe epilepsy. Experiments with the miR-34a antagomir revealed that targeting miR-34a led to an inhibition of activated caspase-3 protein expression, which may contribute to increased neuronal survival and reduced neuronal death or apoptosis. CONCLUSIONS: Our study showed the expression profile of miRNAs in the hippocampus in a rat model of temporal lobe epilepsy and an increase in the expression of the pro-apoptotic miR-34a in post-status epilepticus rats. The results show that miR-34a is up-regulated during seizure-induced neuronal death or apoptosis, and targeting miR-34a is neuroprotective and is associated with an inhibition of an increase in activated caspase-3 protein.