Non-alcoholic fatty liver disease (NAFLD) is a dominant cause of chronic liver disease, but the exact mechanism of progression from simple steatosis to nonalcoholic steatohepatitis (NASH) remains unknown. Here, we investigated the role of exosomes in NAFLD progression. Exosomes were isolated from a human hepatoma cell line treated with palmitic acid (PA) and their miRNA profiles examined by microarray. The human hepatic stellate cell (HSC) line (LX-2) was then treated with exosome isolated from hepatocytes. Compared with controls, PA-treated hepatocytes displayed significantly increased CD36 and exosome production. The microarray analysis showed there to be distinctive miRNA expression patterns between exosomes from vehicle- and PA-treated hepatocytes. When LX-2 cells were cultured with exosomes from PA-treated hepatocytes, the expression of genes related to the development of fibrosis were significantly amplified compared to those treated with exosomes from vehicle-treated hepatocytes. In conclusion, PA treatment enhanced the production of exosomes in these hepatocytes and changed their exosomal miRNA profile. Moreover, exosomes derived from PA-treated hepatocytes caused an increase in the expression levels of fibrotic genes in HSCs. Therefore, exosomes may have important roles in the crosstalk between hepatocytes and HSCs in the progression from simple steatosis to NASH.

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Background: The-Optimal-Lymph-Flow (TOLF) intervention aims to promote lymph flow through therapeutic lymphatic exercises to relieve lymphatic pain, swelling, lymphedema symptoms, and to decrease lymph fluid levels among breast cancer survivors. To enhance the efficacy of the TOLF intervention, an innovative, intelligent, Kinect-enhanced lymphatic exercise intervention (Kinect-TOLF) was developed to teach patients to perform the lymphatic exercises correctly. Objectives: This feasibility trial aimed to determine the feasibility, usability, and effects of the Kinect-TOLF on lymphatic pain, swelling, lymphedema symptoms, and lymph fluid levels. Methods: A single-arm feasibility trial with a pre- and post-test design was employed to recruit 30 breast cancer survivors with persistent lymphatic pain or swelling. Patients received a single training session to learn how to perform the lymphatic exercises using the Kinect-TOLF program. Descriptive statistics, Wilcoxon signed-rank tests, t-test, Spearman’s rank correlation coefficients, linear regressions, and Cohen’s d were performed for data analysis. Qualitative data were assessed for common themes. Results: The Kinect-TOLF was effective in training patients to perform the lymphatic exercises correctly with high user satisfaction. Significant reductions were found in scores of lymphatic pain ( MedΔ = −1.00, CI  = [−1.5, −0.1], P = .004), arm/hand swelling ( MedΔ = −1.00, CI = [−1.5, −0.5], P = .004), total swelling ( MedΔ = −1.5, CI = [−2.0, −1.0], P = .003), number of lymphedema symptoms ( MΔ = −3.8, CI = [−5.5, −2.1], P < .001), and lymphedema symptom severity ( MΔ = −5.3, CI = [−9.5, −1.1], P = .016). A significant reduction in lymph fluid levels was found in mean L-Dex scores ( MΔ = −2.68, CI = [−4.67, −0.69], P = .010). Greater decrease in mean L-Dex scores were found in patients with abnormal lymph fluid levels (L-Dex ≥ 7.1) ( MΔ = −5.19, CI = [−1.75, −8.63], P = .008). Patients’ qualitative feedback supported the results of the study. Conclusions: The Kinect-TOLF is safe, feasible, and effective in reducing lymphatic pain, swelling, lymphedema symptoms, and in decreasing lymph fluid levels. Future research should focus on a randomized clinical trial to confirm the unique or synergistic efficacy of the Kinect-TOLF in comparison with current lymphedema treatment and other forms of exercises or movement therapy. This study was registered in ClinicalTrials.gov with US ClinicalTrials.gov Identifier: NCT03999177.

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