Identification of a natural PLA2 inhibitor from the marine fungus Aspergillus sp. c1 for MAFLD treatment that suppressed lipotoxicity by inhibiting the IRE-1α/XBP-1s axis and JNK signaling

Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

Discussion of Clinical Nursing and Communication Skills for Perioperative Patients with Liver, Gallbladder, Spleen, and Pancreas Illness in Solution Focused Approach / 中国医学伦理学

Objective:To conduct clinical psychological intervention for the perioperative patients through solu-tion focused approach, excavate potential and improve the adaptation ability. Methods: On the basis of establis-hing a good nurse-patient relationship, the application of the solution focused approach was conducted in the peri-operative patients ( description of the problem, the construction of specific aims, and discussion on the exception, giving feedback, and evaluation of progress) . Results:After the intervention of solution focused approach, the pa-tients′negative emotion such as nervousness, anxiety, fear and depression decreased significantly (P <0. 05). Conclusion:Psychological intervention could effectively eliminate the negative mood of patients, improve the doc-tor-patient relationship, dissolve the contradiction between doctors and patients, reduce the incidence of medical disputes, and thereby enhance mutual understanding, trust and respect between doctors and patients, which makes the doctor-patient relationship more harmonious.