Celastrol inhibits oligodendrocyte and neuron ferroptosis to promote spinal cord injury recovery.

BACKGROUND: Spinal cord injury (SCI) is a traumatic injury to the central nervous system and can cause lipid peroxidation in the spinal cord. Ferroptosis, an iron-dependent programmed cell death, plays a key role in the pathophysiology progression of SCI. Celastrol, a widely used antioxidant drug, has potential therapeutic value for nervous system. PURPOSE: To investigate whether celastrol can be a reliable candidate for ferroptosis inhibitor and the molecular mechanism of celastrol in repairing SCI by inhibiting ferroptosis. METHODS: First, a rat SCI model was constructed, and the recovery of motor function was observed after treatment with celastrol. The regulatory effect of celastrol on ferroptosis pathway Nrf2-xCT-GPX4 was detected by Western blot and immunofluorescence. Finally, the ferroptosis model of neurons and oligodendrocytes was constructed in vitro to further verify the mechanism of inhibiting ferroptosis by celastrol. RESULTS: Our results demonstrated that celastrol promoted the recovery of spinal cord tissue and motor function in SCI rats. Further in vitro and in vivo studies showed that celastrol significantly inhibited ferroptosis in neurons and oligodendrocytes and reduced the accumulation of ROS. Finally, we found that celastrol could inhibit ferroptosis by up-regulating the Nrf2-xCT-GPX4 axis to repair SCI. CONCLUSION: Celastrol effectively inhibits ferroptosis after SCI by upregulating the Nrf2-xCT-GPX4 axis, reducing the production of lipid ROS, protecting the survival of neurons and oligodendrocytes, and improving the functional recovery.

The mechanisms of Chuanxiong Rhizoma in treating spinal cord injury based on network pharmacology and experimental verification.

BACKGROUND: Chuanxiong Rhizoma (CR) is a common traditional Chinese medicine (TCM) that has been widely used in the treatment of spinal cord injury (SCI). However, the underlying molecular mechanism of CR is still largely unknown. This study was designed to explore the bioactive components and the mechanism of CR in treating SCI based on a network pharmacology approach and experimental validation. METHODS: First, the active compounds and related target genes in CR were screened from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Subsequently, the corresponding target genes of SCI were collected by the Therapeutic Target Database (TTD) and GeneCards database. A protein-protein interaction (PPI) network was constructed using the STRING database. Furthermore, GO function and KEGG enrichment analysis of the targets were analyzed using DAVID tools. Subsequently, the AutoDock software for molecular docking was adopted to verify the above network pharmacology analysis results between the active components and key targets. Finally, an SCI rat model animal validation experiment was assessed to verify the reliability of the network pharmacology results. RESULTS: There were 7 active ingredients identified in CR and 246 SCI-related targets were collected. Then, 4 core nodes (ALB, AKT1, MAPK1, and EGFR) were discerned via construction of a PPI network of 111 common targets. The KEGG enrichment analysis results indicated that the Ras signaling pathway, estrogen signaling pathway, and vascular endothelial growth factor (VEGF) signaling pathway were enriched in the development of SCI. The results of molecular docking demonstrated that the effects of CR have a strong affinity with the 4 pivotal targets. Experimental validation in a rat model showed that CR could effectively improve the recovery of motor function and mechanical pain threshold after SCI. CONCLUSIONS: In summary, it revealed the mechanism of CR treatment for SCI involve active ingredients, targets and signaling pathways, providing a scientific basis for future investigations into the mechanism underlying CR treating for SCI.

Associated Factors for Osteoporosis and Fracture in Chinese Elderly.

BACKGROUND The factors associated with osteoporosis are poorly understood in the Chinese population. This study aimed to examine the factors associated with osteoporosis and with fractures in a Chinese elderly population. MATERIAL AND METHODS This was a cross-sectional study of elderly people living in Tianjin between 2012 and 2014. Bone mineral density was measured by dual X-ray absorptiometry. The subjects completed a questionnaire about lifestyle habits, personal and family medical history, calcium intake, and exercising. Data were gathered on occurrence of fracture at 5 years or August 2018, whichever occurred first. RESULTS There were 298 individuals with osteoporosis (18.5% male, median age 67 years) and 397 without (46.3% male, median age 62 years). Male sex (OR=0.051, 95% CI: 0.021-0.126), age (OR=1.049, 95% CI: 1.099-1.202), being divorced/widowed (OR=2.445, 95% CI: 1.219-4.904), digestive ulcer history (OR=3.805, 95% CI: 1.539-9.405), family history of hunchback (OR=2.659, 95% CI: 1.145-6.175), family history of osteoarthropathy (OR=4.222, 95% CI: 2.128-8.375), fracture history (OR=2.138, 95% CI: 1.307-3.496), drinking green tea (OR=0.352, 95% CI: 0.217-0.574), and exercising (OR=0.303, 95% CI: 0.193-0.475) were independently associated with osteoporosis. Digestive ulcer history (OR=3.183, 95% CI: 1.178-8.5992), exercising (OR=0.354, 95% CI: 0.139-0.903), and taking calcium supplements during follow-up (OR=0.262, 95% CI: 0.112-0.611) were independently associated with fractures in patients with osteoporosis. CONCLUSIONS Female sex, age, marital status, history of digestive ulcer and fracture, and family history of hunchback and osteoarthropathy are associated with osteoporosis among elderly subjects, while drinking green tea and exercising are inversely associated. Among the patients with osteoporosis, a history of digestive ulcer is associated with fractures, while exercising and taking calcium supplements are inversely associated.

Low­frequency pulsed electromagnetic field promotes functional recovery, reduces inflammation and oxidative stress, and enhances HSP70 expression following spinal cord injury.

Low­frequency pulsed electromagnetic fields (LPEMFs) have been reported to be protective for multiple diseases. However, whether the administration of LPEMFs inhibits inflammation and oxidative stress following spinal cord injury requires further investigation. In the current study, a contusion spinal cord injury model was used and LPEMFs administration was applied to investigate the molecular changes, including inflammation, oxidative stress and heat shock protein 70 (HSP70) levels. The results revealed that LPEMFs significantly promoted functional recovery following spinal cord injury, as demonstrated by an increased Basso, Beattie and Bresnahan score. The results demonstrated that LPEMFs decreased the expression of inflammatory factors, including tumor necrosis factor­α, interleukin­1ß and nuclear factor­κB. Additionally, LPEMFs exposure reduced the levels of inducible nitric oxide synthase and reactive oxygen species, and upregulated the expression of catalase and superoxide dismutase. Furthermore, treatment with LPEMFs significantly enhanced the expression of HSP70 in spinal cord­injured rats. Overall, the present study revealed that LPEMFs promote functional recovery following spinal cord injury, potentially by modulating inflammation, oxidative stress and HSP70.

Moxibustion Treatment for Knee Osteoarthritis: A Systematic Review and Meta-Analysis.

To determine whether the administration of moxibustion is an effective treatment for knee osteoarthritis (KOA).We conducted a search of relevant articles using Medline, EMBASE, the Web of Science, and the Cochrane Library published before October 2015. The Western Ontario and McMaster Universities' Osteoarthritis Index (WOMAC scale) and the short form 36 questionnaire (SF-36 scale) were assessed. Evidence grading was evaluated according to the Grading of Recommendations, Assessment, Development and Evaluation system.Four studies containing 746 participants fulfilled the inclusion criteria in the final analysis. In terms of quality of life (QOL), the meta-analysis of 2 randomized clinical trials (RCTs) showed significantly effects of moxibustion only in bodily pain (BP) compared with those in the control group (n = 348; weighted mean difference [WMD], 4.36; 95% confidence intervals [CIs], 2.27-6.44; P < 0.0001; heterogeneity: χ = 1.53, P = 0.22, I = 34%) in all of the subcategories of the SF-36 scale, with moderate quality. The meta-analysis of the 2 included trials showed that there was not a statistically significant difference in the pain or function subscale for the WOMAC scale when the 2 groups were compared (n = 322; WMD, 17.63; 95% CI, -23.15-58.41; P = 0.40; heterogeneity: χ = 19.42, P < 0.0001, I = 95%), with low or moderate quality separately.The administration of moxibustion can to some extent alleviate the symptoms of KOA. More rigorous, randomized controlled trials are required in the future.

Rivaroxaban for thromboprophylaxis after total hip or knee arthroplasty: a meta-analysis with trial sequential analysis of randomized controlled trials.

Venous thromboembolism (VTE) is the most widespread severe complication after total hip arthroplasty (THA) and total knee arthroplasty (TKA). We conducted this meta-analysis to further validate the benefits and harms of rivaroxaban use for thromboprophylaxis after THA or TKA. We thoroughly searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Trial sequential analysis (TSA) was applied to test the robustness of our findings and to obtain a more conservative estimation. Of 316 articles screened, nine studies were included. Compared with enoxaparin, rivaroxaban significantly reduced symptomatic VTE (P = 0.0001) and symptomatic deep vein thrombosis (DVT; P = 0.0001) but not symptomatic pulmonary embolism (P = 0.57). Furthermore, rivaroxaban was not associated with an increase in all-cause mortality, clinically relevant non-major bleeding and postoperative wound infection. However, the findings were accompanied by an increase in major bleeding (P = 0.02). The TSA demonstrated that the cumulative z-curve crossed the traditional boundary but not the trial sequential monitoring boundary and did not reach the required information size for major bleeding. Rivaroxaban was more beneficial than enoxaparin for preventing symptomatic DVT but increased the risk of major bleeding. According to the TSA results, more evidence is needed to verify the risk of major bleeding with rivaroxaban.

Transcutaneous Electrical Nerve Stimulation in Patients With Knee Osteoarthritis: Evidence From Randomized-controlled Trials.

OBJECTIVES: Transcutaneous electrical nerve stimulation (TENS) has been reported to relieve pain and improve function in patients with knee osteoarthritis. The purpose of this systematic review and meta-analysis was to evaluate the efficacy of TENS for the management of knee osteoarthritis. METHODS: We searched Embase, PubMed, CENTRAL, SIGLE, PEDro, and clinicaltrials.gov, up to June 2014 for literature related to TENS used for the treatment of knee osteoarthritis. Two authors independently screened the searched records based on the title and abstract. Information including the authors, study design, mean age, sex, study population, stimulation frequency (of TENS), outcome measures, and follow-up periods were extracted by the 2 authors. RESULTS: Eighteen trials were included in the qualitative systematic review, and 14 were included in the meta-analysis. TENS significantly decreased pain (standard mean difference, -0.79; 95% confidence interval [CI], -1.31 to -0.27; P<0.00001) compared with control groups. There was no significant difference in the Western Ontario and McMaster Universities Osteoarthritis Index (standard mean differences, -0.13; 95% CI, -0.35 to 0.1; P=0.09) or the rate of all-cause discontinuation (risk ratio, 0.77; 95% CI, 0.48 to 1.22; P=0.94) between the TENS and control groups. DISCUSSION: TENS might relieve pain due to knee osteoarthritis. Further randomized-controlled trials should focus on large-scale studies and a longer duration of follow-up.

Delayed drainage versus autotransfusion drainage and routine drainage after total knee arthroplasty: a comparative study.

BACKGROUND: The purpose of this research is to compare the clinical results of different drainage methods in total knee arthroplasty (TKA). METHODS: This retrospective comparative study included 55 patients who accepted primary unilateral TKA between October 2010 and November 2012. The patients were classified according to the drainage method used: 25 patients in the autotransfusion drainage group, 12 patients in the delayed drainage group, and 18 patients in the routine drainage group. Otherwise, the same operative procedures and postoperative care were applied to all patients. The variables recorded included total amount of postoperative drainage (including intraoperative blood loss); cases of allogenic blood transfusion; body temperatures on postoperative days 1, 3, and 7; and pre- and postoperative hemoglobin level. Some other elements such as postoperative swelling, range of motion, and wound healing were also compared. RESULTS: Patients who underwent autotransfusion were found to have an amount of drainage (799.2 ± 196.7 mL) significantly greater than that in the routine drainage group (666.1 ± 155.0 mL), which in turn was significantly greater than that in the delayed drainage group (381.7 ± 129.2 mL). The postoperative hemoglobin level in the delayed drainage group (91.5 ± 7.9 g/L) was similar to that in the autotransfusion group (92.0 ± 9.6 g/L), while that in the routine drainage group (81.3 ± 9.9 g/L) was significantly lower. The patients in the autotransfusion group were observed to have higher body temperatures than those in the other two groups. In the routine drainage group, eight cases accepted allogenic blood transfusion, and the percentage (44.4%) was significantly higher than that in the other two groups. There were no significant between-group differences in swelling, healing qualities, and range of motion. CONCLUSIONS: Delayed postoperative drainage may reduce blood loss and the chance of allogenic blood transfusion compared with routine drainage and may also reduce the chance of postoperative fever and extra costs compared with autotransfusion.

An Experimental Novel Study: Angelica sinensis Prevents Epidural Fibrosis in Laminectomy Rats via Downregulation of Hydroxyproline, IL-6, and TGF- ß 1.

With laminectomy being widely accepted as the treatment for lumbar disorders, epidural fibrosis (EF) is a common complication for both the patients and the surgeons alike. Currently, EF is thought to cause recurrent postoperative pain after laminectomy or after discectomy. Angelica sinensis is a traditional Chinese medicine which has shown anti-inflammatory, antifibrotic, and antiproliferative properties. The object of this study was to investigate the effects of Angelica sinensis on the prevention of post-laminectomy EF formation in a rat model. A controlled double-blinded study was conducted in sixty healthy adult Wistar rats that underwent laminectomy at the L1-L2 levels. They were divided randomly into 3 groups according to the treatment method, with 20 in each group: (1) Angelica sinensis treatment group, (2) saline treatment group, and (3) sham group (laminectomy without treatment). All rats were euthanized humanely 4 weeks after laminectomy. The hydroxyproline content, Rydell score, vimentin cells density, fibroblasts density, inflammatory cells density, and inflammatory factors expressions all suggested better results in Angelica sinensis group than the other two groups. Topical application of Angelica sinensis could inhibit fibroblasts proliferation and TGF- ß 1 and IL-6 expressions and prevent epidural scar adhesion in postlaminectomy rat model.