Intervertebral disc degeneration (IVDD) is a degenerative and chronic spinal disorder often associated with the older population. Oxidative stress is a major pathogenic factor of aging that results in the apoptosis of nucleus pulposus cells (NPCs) and extracellular matrix (ECM) degradation. Quercetin (QUE), a naturally occurring flavonoid with antioxidant and anti-inflammatory properties, has been studied in research on degenerative diseases. However, the potential effects and mechanisms of action of QUE on IVDD remain unclear. In this study, the effects of QUE on antiapoptosis and ECM metabolism were firstly investigated in TBHP-treated NPCs. Meanwhile, the autophagy inhibitor, 3-MA, and p38 MAPK inhibitor, SB203580, were used in subsequent TBHP-induced NPC experiments to determine whether QUE exerted its protective effects through autophagy and the p38 MAPK/mTOR signaling pathway. Finally, the therapeutic effects of QUE were confirmed in vivo using a rat tail needle puncture-induced model of IVDD. We found that QUE treatment significantly alleviated oxidative stress-decreased cell viability and intracellular ROS levels in NPCs treated with TBHP. Furthermore, treatment with QUE led to a decrease in apoptosis as measured by decreased Bax and increased Bcl-2 expression and PE/7-AAD flow cytometry analysis. QUE also promoted ECM stability as measured by increased collagen II and aggrecan and decreased MMP13 levels. Our results also showed that QUE promoted the expression of autophagy markers beclin-1, LC3-II/I, and decreased p62. Inhibition of autophagy by inhibitor 3-MA may partially reverse the protective effect of QUE on apoptosis and ECM degeneration, indicating that autophagy was involved in the protective effect of QUE in NPCs. Further study confirmed that QUE partially inhibited the p38 MAPK signaling pathway and inhibition of p38 MAPK by SB203580 activated autophagy, indicating that QUE protected NPCs against apoptosis and prevented ECM degeneration via the p38 MAPK-autophagy pathway. Finally, using a rat tail puncture-induced model of IVDD, we confirmed that QUE had a protective effect against IVDD. Our results suggest that QUE could prevent IVDD by modulating p38 MAPK-mediated autophagy and, therefore, is a potential therapeutic strategy in the treatment of IVDD.
Spinal cord injury (SCI) often occurs in young and middle-aged population. The present study aimed to clarify the function of Galectin-3 (Gal-3) in neuroinflammation of SCI. Sprague–Dawley (SD) rat models with SCI were established in vivo. PC12 cell model in vitro was induced by lipopolysaccharide (LPS). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Gene chip were used to analyze the expression levels of genes in the signaling pathway. Histological assessment, ELISA and Western blotting were conducted to evaluate the effects of Gal-3 upon the SCI model. In the in vivo SD rat model, Gal-3 expression level was up-regulated. The inhibition of Gal-3 attenuated the neuroinflammation in SCI model. The inhibition of Gal-3 could also mitigate the neuroinflammation and reactive oxygen species (ROS) in in vitro model. ROS reduced the effect of Gal-3 on oxidative stress in in vitro model. Down-regulating the content of TXNIP decreased the effect of Gal-3 on neuroinflammation in in vitro model. Suppressing the level of NLRP3 could weaken the effect of Gal-3 on neuroinflammation in in vitro model. Our data highlight that the Gal-3 plays a vital role in regulating the severity of neuroinflammation of SCI by enhancing the activation of ROS/TXNIP/NLRP3 signaling pathway. In addition, inflammasome/IL-1β production probably acts as the therapeutic target in SCI.
ObjectiveTo compare the efficacy and safety of the postoperative long‐term effect of the treatment of single‐level cervical spondylosis through anterior cervical discectomy and fusion (ACDF) and artificial cervical disc replacement (ACDR).MethodsThis is a retrospective contrastive study, which was conducted for the period of January 2007 and January 2009 at the Department of Spine Surgery of the First Affiliated Hospital of Xinjiang Medical University. A total of 113 patients were divided into two groups depending on the operation method: ACDF group (fusion group, n = 66) and ACDR group (replacement group, n = 47). The ACDR group comprised of 23 males and 24 females. The age of these patients ranged from 31–60 years, with an average age of 42.89 ± 6.30 years. The ACDF group comprised of 38 males and 28 females. The age of these patients ranged from 28–73 years old, with an average age of 49.38 ± 9.89 years old. The evaluation index included the visual analogue scale (VAS), neck disability index (NDI), range of motion, dysphagia, adjacent vertebral disease, and related complications (prosthesis displacement, heterotopic ossification, etc.).ResultsA total of 113 patients met the inclusion criteria, and these patients receive more than 96 months of follow‐up. The VAS and NDI of these two groups of patients significantly improved, when compared with those before the operation. In the last follow‐up visit, the range of motion in the ACDR group and ACDF group was 43.22 ± 3.58 and 32.54 ± 2.82, respectively, and both are significantly different comparing to the values measured before the operation (P < 0.05). The dysphagia incidence of the ACDR group was higher than that of the ACDF group at the 36th month, but was lower than that of the ACDF group in other points time. In the last follow‐up visit, six patients (12.77%) in the ACDR group and 18 patients (27.27%) in the ACDF suffered from adjacent segment degeneration (ASD). The general complication rate in the replacement group and fusion group was 38.31% and 37.88%, respectively, but the difference between the two groups was not statistically significant (P > 0.05).ConclusionOverall, the clinical efficacy and related complication rate of single‐level cervical spondylosis after an anterior cervical approach operation was superior in the ACDR group when compared to the ACDF group.
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