The regulation of M1/M2 polarization in liver macrophages is closely associated with the progression of nonalcoholic steatohepatitis (NASH); however, the mechanism involved in this process remains unclear. Here, we describe the orphan nuclear receptor retinoic-acid-related orphan receptor α (RORα) as a key regulator of M1/M2 polarization in hepatic residential Kupffer cells (KCs) and infiltrated monocyte-derived macrophages. RORα enhanced M2 polarization in KCs by inducing the kruppel-like factor 4. M2 polarization was defective in KCs and bone-marrow-derived macrophages of the myeloid-specific RORα null mice, and these mice were susceptible to HFD-induced NASH. We found that IL-10 played an important role in connecting the function of M2 KCs to lipid accumulation and apoptosis in hepatocytes. Importantly, M2 polarization was controlled by a RORα activator, JC1-40, which improved symptoms of NASH. Our results suggest that the M2-promoting effects of RORα in liver macrophages may provide better therapeutic strategies against NASH.

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ObjectiveTo evaluate the characteristics of cricopharyngeal dysfunction (CPD), the frequency, and correlation with a brain lesion in patients with first-ever ischemic stroke, and to provide basic data for developing a therapeutic protocol for dysphagia management.MethodsWe retrospectively reviewed the medical records of a series of subjects post-stroke who underwent a videofluoroscopic swallowing study (VFSS) from January 2009 to December 2015. VFSS images were recorded on videotape and analyzed. CPD was defined as the retention of more than 25% of residue in the pyriform sinus after swallowing. The location of the brain lesion was assessed using magnetic resonance imaging.ResultsAmong the 262 dysphagic patients with first-ever ischemic stroke, 15 (5.7%) showed CPD on the VFSS. Patients with an infratentorial lesion had a significantly higher proportion of CPD than those with a supratentorial lesion (p=0.003), and lateral medullary infarction was identified as the single independent predictor of CPD (multivariable analysis: odds ratio=19.417; confidence interval, 5.560–67.804; p<0.0001). Compared to patients without CPD, those with CPD had a significantly prolonged pharyngeal transit time, lower laryngeal elevation, and a higher pharyngeal constriction ratio and functional dysphagia scale score.ConclusionOverall, the results support the notion that an impaired upper esopharyngeal opening is likely related to the specific locations of brain lesions. The association of CPD with lateral medullary infarction can be explained based on the regulation of the pharyngolaryngeal motor system by the motor neurons present in the dorsal nucleus ambiguus. Overall, the results reveal the relation between CPD and the problems in the pharyngeal phase as well as the severity of dysphagia.

This study aimed to investigate the effectiveness of the mobile game-based neuromuscular electrical stimulation (MG-NMES) with assessing usability issues, such as attention and curiosity, and intrinsically interesting issues, which is necessary for successful poststroke rehabilitation. With the conventional NMES (C-NMES) system, the subjects underwent active repetitive cyclic NMES training. For assessment of usability issues, 20 hemiplegic stroke subjects were randomly divided into two groups. The subjects in the MG-NMES group (n = 9) and C-NMES group (n = 11) underwent 20 minutes of training each day for 5 days. We assessed the subjects' attention, curiosity, and intrinsically interesting issues; and using questionnaires they answered questions regarding their expectations of the training outcome after each training session. We found that the subjects in the MG-NMES group maintained their attention and interest for the 5 days, and their curiosity and expectation of a positive training outcome gradually increased as the training proceeded. In contrast, the C-NMES group reported no change in their attention or curiosity, but it was lower than the subjects in the MG-NMES group. In addition, their interest gradually decreased, which may have reduced their expectations of a positive outcome as the sessions progressed. There were no side effects during the training sessions in either group. The MG-NMES training paradigm developed is a new, readily available, and highly motivating MG-NMES training system. Based on the usability test, the reported advantages of the system were improved attention and flow experience during NMES training.

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