Translational research : the journal of laboratory and clinical medicine
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In the present study, we sought to identify long noncoding RNA (lncRNA) expression profiles in nonalcoholic steatohepatitis (NASH) patients with histologic evidence of lobular inflammation and advanced fibrosis. We profiled lncRNA expression using RNA-sequencing of wedge liver biopsies from 24 nonalcoholic fatty liver disease (NAFLD) patients with normal liver histology, 53 NAFLD patients with lobular inflammation, and 65 NAFLD patients with advanced fibrosis. Transcript profiling identified 4432 and 4057 differentially expressed lncRNAs in comparisons of normal tissue with lobular inflammation and fibrosis samples, respectively. ⋯ The expression of MALAT1 and CXCL5 was upregulated in activated hepatic stellate (LX-2) cells compared to cells in the quiescent state, and MALAT1 expression was regulated by hyperglycemia and insulin in HepG2 cells, but only by insulin in LX-2 cells. Dysregulated lncRNA expression is associated with inflammation and fibrosis in NASH. Functionally relevant differences in MALAT1 expression may contribute to the development of fibrosis in NASH through mechanisms involving inflammatory chemokines.
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Pulmonary fibrosis is a relatively rare but devastating disease characterized by the excessive deposition of extracellular matrix. The increased matrix results in reduced lung compliance and increased work of breathing, while the obliteration of alveolar-capillary structures can result in hypoxemia and pulmonary hypertension, which manifests clinically as worsening shortness of breath, respiratory failure, and death. Unbiased genome-wide association studies combined with animal models suggest that damage to the alveolar epithelium is the initiating factor in pulmonary fibrosis. ⋯ We and others have found that mitochondrial and NAD(P)H oxidase-generated reactive oxygen species (ROS) play a signaling role to enhance TGF-β signaling and promote fibrosis. The purpose of this article is to review how ROS signaling leads to the activation of TGF-β. We suggest that an improved understanding of these pathways might explain the failure of nonselective antioxidants to improve outcomes in patients with pulmonary fibrosis and might identify novel targets for therapy.
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Cancer is a major cause of death worldwide, and its incidence and mortality continuously increase in China. Nowadays, cancer heavily influences our health and constitutes enormous burden on society and families. Although there are many tools for cancer treatment, but the overall therapeutic effect is poor. ⋯ Previous studies have reviewed PRRs as promising immunotherapy targets for colorectal cancer and pancreatic cancer. However, until now, a comprehensive review on the role of RLRs in the development and treatment of various cancers is still lacking. In this article, we reviewed the latest studies on the roles as well as the mechanisms of RIG-I and MDA5 in the development of various cancers and therapeutic potentials of targeting RIG-I and MDA5 for cancer treatment.
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Endoplasmic reticulum (ER) stress, a disturbance of the ER function, contributes to cardiac injury. ER and mitochondria are closely connected organelles within cells. ER stress contributes to mitochondrial dysfunction, which is a key factor to increase cardiac injury. ⋯ The cytosolic C/EBP homologous protein (CHOP) content was markedly increased in THAP-treated hearts compared to control, particularly in the nucleus. Metformin prevented the THAP-induced mitochondrial dysfunction and reduced CHOP content in cytosol and nucleus. Thus, metformin reduces cardiac injury during ER stress through the protection of cardiac mitochondria and attenuation of CHOP expression.