RESUMO
Activins belong to the transforming growth factor (TGF)-ß superfamily and are involved in the regulation of homeostasis, proliferation, differentiation, and inflammation. In the present study, we examined the mechanism by which activin regulates the transcription of tumor necrosis factor-α (TNF-α)-stimulated cytokines, chemokines, toll-like receptors (TLRs), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in human umbilical vein endothelial cells (HUVECs), and the involvement of the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Cell viability was analyzed using MTS/PES solution, mRNA expression was measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and protein expression was measured by immunoblotting. TNF-α increased the mRNA expression of cytokines (IL-1ß and IL-6), chemokines (IL-8 and MCP-1), and TLR2, as well as the mRNA and protein expression of iNOS and COX-2. Activin decreased TNF-α-induced cytokine, chemokine, and TLR mRNA expression as well as TNF-α-induced iNOS and COX-2 mRNA and protein expression. In addition, activin suppressed the phosphorylation of NF-κB p65 in TNF-α-stimulated HUVECs and reduced TNF-α-induced phosphorylation of AKT, JNK, ERK, and p38 MAPK. Our results demonstrate that the anti-inflammatory effects of activin are mediated by inflammatory response genes through the inhibition of NF-κB and AKT/JNK/MAPK signaling.
Assuntos
NF-kappa B , Fator de Necrose Tumoral alfa , Ativinas , Quimiocinas , Ciclo-Oxigenase 2/genética , Citocinas , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with elevated mortality. Delay in diagnosis lead to worse outcomes. Guidelines developed at academic medical centers are difficult to replicate in the community. OBJECTIVES: Our primary objective was to ascertain consistency with the 2011 IPF guidelines. Our secondary objective was to conduct an interdisciplinary review to ascertain whether the evidence supported the original diagnosis of IPF or not. METHODS: We asked permission from pulmonologists to review records of patients diagnosed with IPF after 2011. We collected physician demographics and training data; patient demographics, clinical and diagnostic/management data. The clinical data and available images were reviewed by the interdisciplinary review panel. RESULTS: 26 practicing pulmonologists located in the Southeast of the United States consented to participate. Mean age was 48, 70% were male and all had current certification. We reviewed data from 96 patients. The mean age was 71.4 and most were male. Only 23% had the recommended screening for a connective tissue disease and 42.6% were screened for exercise-induced hypoxemia. Among patients with available images for review (n=66), only 50% had a high-resolution CT scan. 22% of patients underwent a surgical biopsy and in only 33% of the cases three lobes were sampled. No patient had documentation that a multidisciplinary discussion occurred. In 20% of the cases with available images, the evidence supported an alternative diagnosis. 56% of eligible candidates were ever started on anti-fibrotics. CONCLUSIONS: Our findings suggest that consistency with the IPF guidelines is low in non-academic settings.
RESUMO
BACKGROUND: Linked color imaging is based on the bioluminescent imaging technique, which enhances differences in mucosal color allowing for contrast-based detection of lesions. There have been reports which have investigated the usefulness of linked color imaging for assessing color values in endoscopy for early gastric cancer cases. However, these primarily focused on differentiated early gastric cancer. This study aimed to assess the efficacy of linked color imaging in analyzing the color differences between cancerous and noncancerous areas in undifferentiated-type early gastric cancer patients compared with conventional white light imaging. METHODS: Forty-six patients were prospectively enrolled with undifferentiated-type early gastric cancer from 3 academic hospitals. All lesions were observed first by white light imaging followed by linked color imaging. An additional biopsy was taken from the surrounding mucosa to check for intestinal metaplasia, and test for Helicobacter pylori was performed. Color difference was measured in accordance with the International Commission on Illumination details. RESULTS: The color difference value with linked color imaging was significantly higher, being more than twice that of white light imaging (26.82 ± 14.18 and 12.60 ± 6.42, P < .001), and this difference appeared to be similar in cases of accompanying Helicobacter pylori infection or intestinal metaplasia. In the subgroup analysis, color difference of poorly differentiated adenocarcinoma was notable in linked color imaging compared to white light imaging. Conversely, no statistically significant finding was present in signet ring cell carcinoma or mixed-type histology. CONCLUSION: Linked color imaging provides a significantly greater color difference between cancerous lesions and background noncancerous mucosa in undifferentiated-type early gastric cancer. Moreover, linked color imaging may differentiate between pathologic subgroups of undifferentiated-type early gastric cancer possibly due to characteristic cellular growth pattern.
Assuntos
Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Infecções por Helicobacter/diagnóstico , Endoscopia Gastrointestinal/métodos , Mucosa Gástrica/diagnóstico por imagem , Mucosa Gástrica/patologia , Metaplasia/diagnóstico por imagem , Metaplasia/patologia , Cor , Detecção Precoce de CâncerRESUMO
OBJECTIVES: The role of autophagy in the pathophysiology of otitis media with effusion (OME) remains unclear, particularly regarding the difference between pediatric and adult patients. The present study analyzed the expression levels of autophagy-associated mRNAs in effusion fluids obtained from pediatric and adult patients with OME. MATERIALS AND METHODS: Middle ear fluid samples were collected from 76 pediatric patients and 41 adult patients with OME, and the levels of mRNAs encoding autophagy-related genes were measured using real-time reverse transcription-polymerase chain reaction. The relationships between the levels of autophagy-associated mRNAs and the frequency of ventilation tube insertion, the characteristics of middle ear fluid, and the results of bacterial culture were analyzed. RESULTS: Autophagy-associated mRNAs were present in the effusion fluid of all patients. The level of Beclin-1 mRNA was significantly lower in pediatric than in adult patients, regardless of the frequency of surgery or fluid characteristics (p < 0.05). CONCLUSION: Autophagy-associated mRNAs were expressed in effusion fluids of both pediatric and adult patients with OME. However, the level of Beclin-1 mRNA was significantly lower in the effusion fluid of pediatric than adult patients.