Identification of biomarkers and candidate small-molecule drugs in lipopolysaccharide (LPS)-induced acute lung injury by bioinformatics analysis

Background/objective: Acute lung injury (ALI) is a critical clinical syndrome with high rates of incidence and mortality. However, its molecular mechanism remains unclear. The current work aimed to explore the molecular mechanisms of ALI by identifying different expression genes (DEGs) and candidate drugs using a combination of chip analysis and experimental validation. Methods: Three microarray datasets were downloaded from Gene Expression Omnibus (GEO) database to obtain DEGs. We conducted a Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway-enrichment analyses of overlapping DEGs among three databases. The expression level of key gene was verified by Western blotting analysis in LPS-treated ALI cell models. Finally, we predicted the candidate drugs targeting the key gene that might be effective for ALI treatment, and the role of candidate drug in treating ALI was verified by investigation. Results: A total 29 overlapping DEGs were up-regulated in LPS-induced ALI groups. They were enriched in inflammation and inflammation-related pathways. Serpin family A member 3 (SERPINA3) was defined as a key gene because it was associated with inflammation pathway and up-regulated in microarray datasets in LPS-induced ALI. In LPS-induced human bronchial epithelial cells transformed with Ad12-SV40-2B (BEAS-2B) cells, SERPINA3 was enhanced. Pyridoxal phosphate as an upstream drug of SERPINA3 could improve cell viability and reduce expression inflammatory factors in LPS-treated BEAS-2B cells. Conclusion: Our study suggested that pyridoxal phosphate could be a candidate drug targeting SERPINA3 gene in LPS-induced ALI. It has protective and anti-inflammatory effects in BEAS-2B cells, and may become a potential novel treatment for ALI (AU)

Vaspin attenuates steatosis-induced fibrosis via GRP78 receptor by targeting AMPK signaling pathway

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that is rapidly becoming a public health problem. An imbalance in lipid distribution to the hepatocytes and metabolism causes hepatocyte steatosis. Vaspin is a newly discovered adipokine that has been linked to a variety of metabolic disorders. The effects of vaspin on steatosis and fibrosis pathogenesis and related mechanisms are unclear. Thus, this study investigated the molecular mechanism of vaspin on hepatocyte steatosis and fibrosis. HepG2 cells were treated with 1.2 mM free fatty acid and the intracellular lipid values were measured by flow cytometry and Nile red assay. RT-qPCR was used to assess the effect of vaspin and blocking of the GRP78 receptor on the expression of lipogenesis, oxidation, uptake, and secretion of fatty acid (FA), as well as AMPK activity. In co-cultured HepG2 and LX-2 cell lines, the expression of main proteins of hepatocyte fibrosis was analyzed using Western blot analysis. In the HepG2 cell line, we discovered that vaspin increased oxidation, FA secretion and gene expression, and AMPK activity and decreased lipogenesis and FA uptake and gene expression. Western blot analysis in co-cultured HepG2 and LX-2 cell lines showed that α-SMA and TGF-β1 protein expression decreased. The data demonstrated that vaspin acts as a novel regulator of hepatocyte steatosis through the GRP78 receptor, effectively reducing hepatocyte fibrosis through AMPK activation and decreasing NF-κB gene expression. (AU)

Expression levels of SCCA and CYFRA 21-1 in serum of patients with laryngeal squamous cell carcinoma and their correlation with tumorigenesis and progression

Purpose To explore the concentration of squamous cell carcinoma antigen (SCCA), cytokeratin fragment antigen 21-1 (CYFRA21-1) in patients with laryngeal squamous cell carcinoma (LSCC) and its correlation with tumorigenesis and progression. Methods A total of 78 patients with LSCC admitted to our hospital from February 2010 to January 2016 were enrolled as the research group (RG), and another 41 healthy volunteers from the same period were selected as the control group (CG). The serum concentrations of SCCA and CYFRA21-1 in patients with LSCC were detected by ELISA, whose diagnostic value in LSCC were further analyzed by ROC curve. The prognosis and survival curves of patients with LSCC were observed according to the median value of serum SCCA and CYFRA21-1 concentrations. Results The concentration of CYFRA21-1 and SCCA in the RG was significantly higher than that in the CG (p < 0.050). The SCCA and CYFRA21-1 identified a significant difference in smoking, lymphatic metastasis, TNM staging, and differentiation degree (p < 0.050). The survival rate of the SCCA low-concentration group was significantly better than that of the high-concentration group, p < 0.050. The survival rate of the CYFRA21-1 low-concentration group was markedly better than that of the high-concentration group, p < 0.050. Conclusions SCCA and CYFRA21-1 are highly concentrated in LSCC patients, which have good diagnostic efficacy for LSCC. In addition, they play some certain role in the occurrence and development of LSCC, and are expected to be markers for early diagnosis and prognosis of this disease. (AU)

Una visión inmunológica del déficit de alfa 1 antitripsina / No disponible

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Relación entre el sistema fibrinolítico y las enfermedades neurológicas / Relationship between fibrinolytic system and neurological diseases

Introducción. El sistema fibrinolítico, o sistema del plasminógeno, se compone de una serie de moléculas que convierten el plasminógeno en su forma activa plasmina, la cual es capaz de participar en múltiples procesos fisiopatológicos. Objetivo. Realizar una revisión de la bibliografía y analizar la relación entre el sistema fibrinolítico y las enfermedades neurológicas y sus posibles implicaciones terapéuticas al respecto. Desarrollo. El sistema fibrinolítico se ha involucrado en muy diversas patologías. Aunque tradicionalmente se pensaba que su relación con las enfermedades neurológicas era escasa, en los últimos años se han establecido importantes nexos de unión. De esta forma, el sistema fibrinolítico parece estar involucrado no solamente en enfermedades cerebrovasculares, sino también en la epilepsia, enfermedades neurodegenerativas, como la enfermedad de Alzheimer, enfermedades de perfil inflamatorio, como la esclerosis múltiple, alteraciones del sistema dopaminérgico, trastornos del aprendizaje o enfermedades del sistema nervioso periférico. Diferentes genotipos de los componentes de este sistema se han mostrado como factores protectores o de riesgo para el desarrollo de estas enfermedades, y la información acumulada a este respecto está aumentando sustancialmente. Conclusiones. Un mayor conocimiento de las relaciones entre el sistema fibrinolítico con las enfermedades neurológicas podría aclarar ciertos puntos sobre su fisiopatología y también suponer futuras líneas de prevención y tratamiento (AU)

Introduction. The fibrinolytic system, also named plasminogen system is formed by a group of molecules that transforms plasminogen in its active form plasmine, which is able to participate in a number of pathophysiological processes. Aim. To carry out a review of the literature and an analysis of the relationship between fibrinolytic system and neurological diseases and its potential therapeutic implications.Development. The fibrinolytic system has been involved in many different pathologies. Although its role in neurological diseases has always been thought to be scarce, many relations have been recently established. This way, fibrinolytic system seems to be involved not only in cerebrovascular diseases but also in epilepsy, inflammatory diseases such as multiple sclerosis, alterations of the dopaminergic system, learning disorders and several lesions of the peripheral nervous system. Different genotypes of several components of this system have been related as risk or protector factors to the development of these neurological diseases and information to this respect is rapidly increasing. Conclusions. A better knowledge about the relations between the fibrinolytic system and neurological diseases could clarify several aspects about their pathophysiology and it could suppose future prevention and treatment lines (AU)

Terapia antiangiogénica / Antiangiogenic therapy

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