In this study, we aimed to study the role of growth factor receptor-bound protein 2 (Grb2) in palmitic acid-induced steatosis and other "fatty liver" symptoms in vitro. HepG2 cells, with or without stably suppressed Grb2 expression, were incubated with palmitic acid for 24 h to induce typical clinical "fatty liver" features, including steatosis, impaired glucose metabolism, oxidative stress, and apoptosis. MTT and Oil Red O assays were applied to test cell viability and fat deposition, respectively. Glucose uptake assay was used to evaluate the glucose utilization of cells. Quantitative polymerase chain reaction and Western blot were used to measure expressional changes of key markers of insulin signaling, lipid/glucose metabolism, oxidative stress, and apoptosis. After 24-h palmitic acid induction, increased fat accumulation, reduced glucose uptake, impaired insulin signaling, enhanced oxidative stress, and increased apoptosis were observed in HepG2 cells. Suppression of Grb2 in HepG2 significantly reduced fat accumulation, improved glucose metabolism, ameliorated oxidative stress, and restored the activity of insulin receptor substrate-1/Akt and MEK/ERK pathways. In addition, Grb2 deficiency attenuated hepatic apoptosis shown by reduced activation of caspase-3 and fluorescent staining. Modulation of Bcl-2 and Bak1 also contributed to reduced apoptosis. In conclusion, suppression of Grb2 expression in HepG2 cells improved hepatic steatosis, glucose metabolism, oxidative stress, and apoptosis induced by palmitic acid incubation partly though modulating the insulin signaling pathway.
There is a need to provide a more effective user interface to facilitate non-domain experts' health information seeking in authoritative online databases such as MEDLINE. We developed a new topic cluster based information navigation system called SimMed. Instead of offering a list of documents, SimMed presents users with a list of ranked clusters. Topically similar documents are grouped together to provide users with a better overview of the search results and to support exploration of similar literature within a cluster. We conducted an empirical user study to compare SimMed to a traditional document list based search interface. A total of 42 study participants were recruited to use both interfaces for health information exploration search tasks. The results showed that SimMed is more effective in terms of users' perceived topic knowledge changes and their engagement in user-system interactions. We also developed a new metric to assess users' efforts to find relevant citations. On average, users need significantly fewer clicks to find relevant information in SimMed than in the baseline system. Comments from study participants indicated that SimMed is more helpful in finding similar citations, providing related medical terms, and presenting better organized search results, particularly when the initial search is unsatisfactory. Findings from the study shed light on future health and biomedical information retrieval system and interface designs.
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