Background: Hericium erinaceus is an edible mushroom; its various pharmacological effects which have been investigated. This study aimed to demonstrate whether efficacy of oral administration of H. erinaceus mycelium (HEM) and its isolated diterpenoid derivative, erinacine A, can act as an anti-neuroinflammatory agent to bring about neuroprotection using an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinson’s disease, which results in motor disturbances, in addition to elucidating the mechanisms involved. Methods: Mice were treated with and without HEM or erinacine A, after MPTP injection for brain injuries by the degeneration of dopaminergic nigrostriatal neurons. The efficacy of oral administration of HEM improved MPTP-induced loss of tyrosine hydroxylase positive neurons and brain impairment in the substantia nigra pars compacta as measured by brain histological examination. Results: Treatment with HEM reduced MPTP-induced dopaminergic cell loss, apoptotic cell death induced by oxidative stress, as well as the level of glutathione, nitrotyrosine and 4-hydroxy-2-nonenal (4-HNE). Furthermore, HEM reversed MPTP-associated motor deficits, as revealed by the analysis of rotarod assessment. Our results demonstrated that erinacine A decreases the impairment of MPP-induced neuronal cell cytotoxicity and apoptosis, which were accompanied by ER stress-sustained activation of the IRE1α/TRAF2, JNK1/2 and p38 MAPK pathways, the expression of C/EBP homologous protein (CHOP), IKB-β and NF-κB, as well as Fas and Bax. Conclusion: These physiological and brain histological changes provide HEM neuron-protective insights into the progression of Parkinson’s disease, and this protective effect seems to exist both in vivo and in vitro.

Homocysteine and pro-inflammatory mediators such as cyclooxygenase-2 (COX-2) have been linked to vascular dysfunction and risks of cardiovascular diseases. Fulvic acid (FA), a class of compounds of humic substances, possesses various pharmacological properties. However, the effect of FA on inflammatory responses of the monocytes remains unclear. We investigated the regulatory effect of FA on homocysteine-induced COX-2 expression in human monocytes. Peripheral blood monocytes and U937 cells were used for all experiments. Real-time PCR and ELISA assay were used to analyze the COX-2 mRNA expression and PGE2 secretion, respectively. Specific inhibitors were used to investigate the mechanism of homocysteine-mediating COX-2 mRNA expression and PGE2 secretion. Luciferase assay, transcription factor ELISA, and chromatin immunoprecipitation were used to determine the role of nuclear factor-κB in FA-mediated inhibition of homocysteine effect on monocytes. The results show that pretreating monocytes with FA inhibited the homocysteine-induced COX-2 expression in a dose-dependent manner. Stimulation of U937 monocytes with homocysteine induced rapid increases in the phosphorylation of ERK and JNK; the inhibitor for ERK and JNK attenuated the homocysteine-induced nuclear factor-κB activation and COX-2 expression. Transcription factor ELISA and chromatin immunoprecipitation assays showed that FA blocked the homocysteine-induced increases in the binding activity and in vivo promoter binding of nuclear factor-κB in monocytes. Our findings provide a molecular mechanism by which FA inhibits homocysteine-induced COX-2 expression in monocytes, and a basis for using FA in pharmaceutical therapy against inflammation.

Objectives: Objective structured clinical examinations (OSCEs) are common for formative assessment. We developed an Online Smart Communicative Education System and aimed to explore the factors that affect the perceptions of both teachers and students for teaching and learning.Methods and Analysis: A two-year cross-sectional cohort study was undertaken. The program includes three parts. Part I Pre-OSCE: an online flipped class in preparation for task-related knowledge and skills. Part II OSCE-day: 10 tasks in one track formative OSCE. Part III Post-OSCE: extended online feedback for participants with further questions after the exam and raters with more feedback after reviewing their performance online. Principal component analysis with varimax rotation was performed to analyze the perceptions of students and teachers to the Online System by means of questionnaires.Results: Seventy-six pharmacy students (male 32.9%) took the exam and 24 raters (male, 25%) participated in the scoring during the OSCEs. The mean G coefficient was 0.88. Seventy-six questionnaires from the students were obtained for the analysis. Results explained the cumulative variance of 73.9% for component (1) “Effects of extended online feedback”: 40% and (2) “Facilitation of learning”: 33.9%. Thirty-nine questionnaires from the raters who experienced the Online System were obtained for the analysis (male 23.1%). Results explained a cumulative variance of 77.3% for component (1) “Effects of extended online feedback”: 36.6%, (2) “Facilitation of scoring and feedback”: 24.5%, and (3) “Feasibility of online platform”: 16.2%, respectively.Conclusion: We demonstrated good reliability for digitizing the scoring system with educational support to facilitate teaching. “Effects of extended online feedback” was the major aspect in explaining the variance from the perceptions of students and raters by factor analysis. In comparison with traditional formative OSCEs, extended online feedback is a novel approach, which extends the process of learning and teaching among the learners and raters and overcomes the barriers of time limitation and distance.

The resistance of renal cell carcinoma (RCC) to sunitinib impedes the success of chemotherapy in cancer treatment. Although several sunitinib resistance mechanisms have been proposed, little is known concerning the impact of obesity and adipokines in RCC cells. The upregulation of sterol-regulatory element-binding protein-1 (SREBP-1) has been reported to modulate the progression of tumor cells. The present study investigated the effect of visfatin on sunitinib-induced cytotoxicity in RCC cells through SREBP-1 expression. We found that visfatin-induced Akt and p70S6K activation increased SREBP-1 expression in 786-O cells. The visfatin-induced SREBP-1 mRNA and protein levels were attenuated through the inactivation of Akt and p70S6K by pharmacological inhibitors. In addition, the SREBP-1 knockdown using siRNA enhanced the cytotoxic effects of sunitinib. Our results also revealed the roles of simvastatin in attenuating the effects of visfatin on 786-O cells by inhibiting the production of reactive oxygen species. In particular, simvastatin co-treatment increased the cell cytotoxicity of sunitinib in visfatin-treated 786-O cells, which were associated with down-regulation of SREBP-1 expression. Our results suggest an important role of SREBP-1 in visfatin-induced drug resistance of RCC cells to sunitinib. The cytotoxic mechanism of simvastatin on RCC cells may provide a new strategy to improve therapeutic outcomes for the RCC treatment.