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Intervertebral disc degeneration (IDD) remains a leading cause of adult disability. High mobility group box l (HMGB1) is a nuclear DNA-binding protein and acts as a central mediator of inflammation. The purpose of this study was to investigate the effect of HMGB1 in IDD. In our study, IDD intervertebral disc tissues were collected and nucleus pulposus cells (NPCs) were primarily cultured. The HMGB1 expression and the effect of HMGB1 on NPCs and extracellular matrix and autophagy were all evaluated. Results showed that HMGB1 was markedly overexpressed in IDD ( P <0.05), and upregulated expression of HMGB1 can inhibit NPC proliferation and promote NPC apoptosis ( P <0.05), promote extracellular matrix degradation, and activate cell autophagy ( P <0.05). Therefore, we concluded that HMGB1 was up-regulated in IDD and HMGB1-induced autophagy can promotes extracellular matrix degradation and thus lead to intervertebral disc degeneration. In brief, HMGB1 may serve as a novel diagnostic biomarker and therapeutic target for IDD., Competing Interests: None., (IJCEP Copyright © 2020.)

Objective: To observe the change in expression of Toll-like receptor 4 (TLR4) of splenic macrophage in patients with hypersplenism due to portal hypertension (PH), and investigate the role of TLR4 of splenic macrophage in hypersplenism., Methods: Splenectomy was performed on 20 patients with hypersplenism due to PH (hypersplenism group) and 6 patients with rupture of spleen by trauma (control group) and the specimens of spleen were collected. The splenic macrophages were isolated by adhibit wall method. The expression of TLR4 of splenic macrophage was detected by immunohistochemical method (SABC), and the result was analyzed by the image analysis system. The phagocytosis of splenic macrophage was measured by chicken red blood cell (CRBC) phagocytosis assay. The level of serum endotoxin was detected before the operation by limulus assay. The results of these 2 groups were compared, and correlation analysis was made among different results of the hypersplenism group., Results: The expression of TLR4 of splenic macrophage was 109 +/- 32 in the hypersplenism group, significantly higher than that of the control group (62 +/- 5, P < 0.01). The rate of phagocytosis and index of phagocytosis of splenic macrophage in the hypersplenism group were 12.6% +/- 3.0% and 0.146 +/- 0.035 respectively, both significantly higher than those of the control group (6.9% +/- 0.5% and 0.076 +/- 0.008 respectively, both P < 0.01) The level of endotoxin of the hypersplenism group was 0.28 EU/ml +/- 0.21 EU/ml, significantly higher than that of the control group (0.054 EU/ml +/- 0.014 EU/ml, P < 0.05). The rate of phagocytosis and the index of phagocytosis of splenic macrophage were notably positively correlated with the expression of TLR4 (r = 0.601, P < 0.01 and r = 0.553, P < 0.05), and the level of endotoxin (r = 0.724 P < 0.01 and r = 0.506, P < 0.05). The expression of TLR4 of splenic macrophage was positively correlated with the level of endotoxin (r = 0.525, P < 0.05)., Conclusion: The expression of TLR4 of splenic macrophage in patients with hypersplenism due to PH was increased significantly. It may be one of the important factors of hypersplenism due to PH that "endotoxemia-->increase of expression of TLR4 of splenic macrophage (activation of TLR of splenic macrophage)-->increased destruction of red blood cells by macrophage".