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.
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.
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.
Abstract. In recent years accumulating evidence has indicated that tocotrienol exhibits an oxidation resistance function, decreased cholesterol function, inhibits cancer function and has unique physiological functions, including anti-inflammatory, anti-apoptotic and anti-oxidative properties. The present study investigated the effect of tocotrienols on spinal cord injury (SCI) by evaluating oxidative stress, inflammation and inducible nitric oxide synthase (iNOS) in rats. A rat model of SCI was induced by operation. SCI rats were treated with 120 mg/kg/day tocotrienol once a day for eight consecutive weeks. Functional recovery following SCI was measured by using the Basso Beattie Bresnahan (BBB) locomotor rating scale. Then the volume of spinal cord contusions was measured following induction of SCI in the rats. In SCI rats, serum malondialdehyde, superoxide dismutase, catalase, glutathione peroxidase, nuclear factor-κB p65 unit, tumor necrosis factor-α, interleukin (IL)-1β and IL-6 levels were analyzed using respective commercial immunoassay kits. Firstly, iNOS, transforming growth factor (TGF)-β, collagen type IV and fibronectin protein expression levels, in addition to iNOS activity and plasma nitric oxide (NO) production in SCI rats was analyzed using western blot analysis, commercial kits and Griess reagent, respectively. Tocotrienol treatment elevated BBB scores and contused volume in the SCI rats. Tocotrienol protected against SCI with reduced oxidative stress and inflammation, and inhibited iNOS protein expression iNOS activity and plasma NO production in rats. In addition, treatment with tocotrienols suppressed TGF-β, collagen type IV and fibronectin protein expression levels in SCI rats. These results suggest that tocotrienols protect SCI, and suppress oxidative stress, inflammation and iNOS in this model of SCI through TGF-β, collagen type IV and fibronectin signaling pathways.
Brucellar spondylodiscitis, the most prevalent and significant osteoarticular presentation of human Brucellosis, is difficult to diagnose and usually yields irreversible neurologic deficits and spinal deformities. However, no animal models of Brucellar spondylodiscitis exist, allowing for preclinical investigations. The present study investigated whether intraosseous injection of attenuated Brucella melitensis vaccine into rabbits' lumbar vertebrae imitates the radiographic and histopathological characteristics of human Brucellar spondylodiscitis. Radiographic and histopathological analyses at 8 weeks postoperatively revealed radiographic changes within vertebral bodies and intervertebral discs, abscesses formation within the paravertebral soft tissue, and typical prominent inflammation response without caseous necrosis, which were largely comparable to human Brucellar spondylodiscitis. Such a medium-sized, surgically feasible rabbit model provides a promising in vivo setting for further preclinical investigation of Brucellar spondylodiscitis.
Background:The findings regarding association of endoplasmic reticulum aminopeptidase 1 (ERAP1) gene polymorphisms and ankylosing spondylitis (AS) susceptibility are inconsistent. Our aim is to appraise and merge the existing evidence on the relationship of rs27044 and rs30187 polymorphisms in ERAP1 gene and susceptibility to AS.Methods: Electronic databases of PubMed, Web of Science, EMBASE, Cochrane Library, Wanfang, and CNKI were retrieved for relevant publications. The search was conducted from inception to 10 June, 2019. Studies on the association of rs27044 and rs30187 polymorphisms and risk of AS were included. Quality evaluation was carried out using Newcastle-Ottawa Scale (NOS). Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to appraise the associations under allelic and genotypic models. Results:In total, 26 case-control studies with 31 cohorts containing 17 223 AS patients and 36 915 controls were eligible for this meta-analysis. According to NOS, each study received ≥ 5 scores. The pooled data indicated that rs27044 and rs30187 polymorphisms were significantly associated with AS susceptibility in the overall population: rs27044, G versus C, OR = 1.24, 95% CI 1.16-1.33, P<.001; rs30187, T versus C, OR = 1.24, 95% CI 1.17-1.33, P<.001. When stratified by ethnicity, rs27044 appeared to be significantly correlated with AS in both Asians and Caucasians. For rs30187, despite positive association being observed under the allelic model in both Asians and Caucasians, the findings of genotypic comparisons supported the association only existed in Caucasians but not Asians. Conclusion:This study suggests that rs27044 and rs30187 polymorphisms are significantly associated with increased risk of AS, especially in Caucasians. K E Y W O R D Sankylosing spondylitis, ERAP1, meta-analysis, polymorphism | INTRODUC TI ONAnkylosing spondylitis (AS) is a chronic inflammatory condition which typically affects the axial skeleton and sacroiliac joints.Clinical features of AS include fatigue, spinal stiffness, limitation in activities, and serious back pain. 1 The prevalence of AS is estimated to be 0.74-3.19 per 1000 across different populations. 2 AS mainly strikes individuals at the age of late teens to early twenties and
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