Factors Associated With Pain Catastrophizing in Patients With Chronic Neuropathic Pain: A Cross-Sectional Study.

BACKGROUND: Pain catastrophizing is a significant factor in the recovery of patients with chronic pain. This topic has not received the warranted attention in clinical practice, while the outcomes of pain interventions have been suboptimal. This study explores the current situation of pain catastrophizing in patients with chronic neuropathic pain, its influencing factors, and further analyzes the complex relationship between these factors. METHODS: A cross-sectional study design was used to select preoperative patients hospitalized in the pain and spine surgery departments of two tertiary hospitals in Shandong Province, China, between February and August 2022. The Pain Catastrophizing Scale, Toronto Alexithymia Scale, Connor-Davidson Resilience Scale-Short, Somatization Sub-Scale of Symptom Checklist 90, and a sociodemographic questionnaire were used to evaluate participants' pain catastrophizing, alexithymia, psychological resilience, somatization, and relevant sociodemographic variables, respectively. Descriptive statistics, correlation, univariate, and multivariate analyses were employed throughout this process. RESULTS: Pain catastrophizing in patients with chronic neuropathic pain was affected by pain severity, disease type, alexithymia, psychological resilience, and somatization (p < .05). The mediating effect values of psychological resilience and somatization between alexithymia and pain catastrophizing were both 0.05, with 95% confidence intervals of (0.02, 0.09) and (0.02, 0.07), respectively. CONCLUSIONS: Pain severity, disease type, alexithymia, psychological resilience, and somatization all had a significant effect on pain catastrophizing. Healthcare workers must provide timely and accurate assessments of patients' pain levels to help prevent the onset of pain catastrophizing. Adopting measures to improve alexithymia and somatization symptoms, and focusing on enhancing patients' psychological resilience can also help reduce the level of pain catastrophizing. Cognitive behavioral therapy may be an effective treatment method for pain catastrophizing.

Causal relationships between delirium and Parkinson's disease: a bidirectional two-sample Mendelian randomization study.

BACKGROUND: Previous observational studies have suggested a notably elevated prevalence of delirium in individuals diagnosed with Parkinson's disease (PD), thereby implying a potential increased susceptibility to delirium among PD patients. However, it is imperative to acknowledge that observational studies inherently possess limitations, rendering it arduous to establish a definitive causal or reverse causal association between delirium and PD. METHODS: To explore the relationship between delirium and PD, a bidirectional two-sample Mendelian randomization (MR) was conducted using summary statistics obtained from genome-wide association studies. The main analysis was performed using the inverse-variance weighted (IVW) method, with further analyses conducted using MR Egger, weighted median, and weighted mode to ensure accuracy of findings. Additionally, Cochran's Q statistics and MR Egger intercept were utilized to assess heterogeneity and horizontal pleiotropy, respectively. RESULTS: According to the results obtained from the IVW model, no compelling evidence was found to support a potential causal association between delirium and PD (IVW: odds ratio [OR]: 0.996, 95% confidence interval CI 0.949-1.043, P = 0.845). Additionally, in the reverse direction, based on the results obtained from the IVW model, no significant evidence was found to support a causal association between PD and delirium (IVW: OR: 1.078, 95%CI 0.960-1.204, P = 0.225). A sensitivity analysis verified the reliability of the results. CONCLUSION: According to the MR findings, a bidirectional causal relationship between delirium and PD is not observed. It is crucial to conduct further research in clinical practice to investigate the association between delirium and the risk of PD.

Preparation of superhydrophobic sponge and its application in oil-water separation and treatment of polymer-containing wastewater.

At present, the application prospect of superhydrophobic materials in oil-water separation, an-tibacterial and other aspects have attracted more and more attention. However, preparing a simple and low-cost superhydrophobic material remains a challenge. Using acetone as solvent, candle soot, silver/silica nanoparticles and polydimethylsiloxane were uniformly mixed to form a mixed solution, and the superhydrophobic sponge was successfully prepared by spraying method. The results show that the superhydrophobic sponge has high water contact Angle (162°) and excellent oil-water separation efficiency, which can realize effective treatment of polymerized wastewater. In addition, the superhydrophobic sponge showed better antibacterial properties on the surface of Escherichia coli and Staphylococcus aureus. In this work, a simple way to prepare superhydro-phobic oil-water separation material is proposed. The preparation process is green, the material is easy to obtain, and it is expected to be widely used in practical production.

Can you notice my attention? A novel information vision enhancement method in MR remote collaborative assembly.

In mixed reality (MR) remote collaborative assembly, remote experts can guide local users to complete the assembly of physical tasks by sharing user cues (eye gazes, gestures, etc.) and spatial visual cues (such as AR annotations, virtual replicas). At present, remote experts need to carry out complex operations to transfer information to local users, but the fusion of virtual and real information makes the display of information in the MR collaborative interaction interface appear messy and redundant, and local users sometimes find it difficult to pay attention to the focus of information transferred by experts. Our research aims to simplify the operation of remote experts in MR remote collaborative assembly and to enhance the expression of visual cues that reflect experts' attention, so as to promote the expression and communication of collaborative intention that user has and improve assembly efficiency. We developed a system (EaVAS) through a method that is based on the assembly semantic association model and the expert operation visual enhancement mechanism that integrates gesture, eye gaze, and spatial visual cues. EaVAS can give experts great freedom of operation in MR remote collaborative assembly, so that experts can strengthen the visual expression of the information they want to convey to local users. EaVAS was tested for the first time in an engine physical assembly task. The experimental results show that the EaVAS has better time performance, cognitive performance, and user experience than that of the traditional MR remote collaborative assembly method (3DGAM). Our research results have certain guiding significance for the research of user cognition in MR remote collaborative assembly, which expands the application of MR technology in collaborative assembly tasks.

Embelin protects against apoptosis and inflammation by regulating PI3K/Akt signaling in IL-1ß-stimulated human nucleus pulposus cells.

Embelin is a natural benzoquinone compound that displays a beneficial effect in various inflammatory-related diseases. However, the effect of embelin on degeneration of intervertebral disc (IDD), a chronic inflammatory disorder, has not been reported. This study was attempted to explore the therapeutic action of embelin on IDD in vitro. Network pharmacology analysis was performed for evaluating the link between embelin and IDD. The human nucleus pulposus cells (NPCs) were stimulated with IL-1ß to induce inflammation. Cell viability of NPCs was assessed by CCK-8 assay. Western blotting was conducted to detect the expression levels of PI3K, p-PI3K, Akt, p-Akt, cleaved caspase-3, caspase-3, Bax, Bcl-2, p65 and p-p65. Apoptotic deaths of NPCs were examined by TUNEL assay. The production of COX-2, IL-6, IL-8, and TNF-α was examined by ELISA. It can be seen that 16 overlapping genes were selected from 109 possible targets of embelin and 342 possible targets of IDD. KEGG pathway enrichment analysis showed that the PI3K/Akt signaling pathway was a close link between embelin and IDD. We found that embelin dose-dependently improved the cell viability in IL-1ß-stimulated NPCs. Embelin elevated the relative levels of p-PI3K/PI3K and p-Akt/Akt in IL-1ß-stimulated NPCs. IL-1ß induced a significant increase in apoptotic deaths of NPCs, which was attenuated by embelin treatment. IL-1ß-induced alternations in expression levels of apoptotic-related proteins including cleaved caspase-3, Bax and Bcl-2 were prevented by embelin treatment. Pretreatment with LY294002 (an inhibitor of PI3K) reversed the inhibitory effect of embelin on IL-1ß-induced apoptosis in NPCs. Embelin treatment caused inhibitory effects on the IL-1ß-stimulated production of COX-2, IL-6, IL-8, and TNF-α, which were abolished by LY294002 treatment. Furthermore, embelin treatment prevented IL-1ß-induced phosphorylation of p65 in NPCs, while LY294002 elevated the embelin-caused decrease in p-p65/p65 level. Overall, embelin protected human NPCs against IL-1ß-stimulated apoptosis and inflammation by regulating the PI3K/Akt signaling pathway. These findings provided new ideas for the clinical usage of embelin in the prevention and treatment of IDD.

Baicalin suppresses interleukin-1ß-induced apoptosis, inflammatory response, oxidative stress, and extracellular matrix degradation in human nucleus pulposus cells.

OBJECTIVE: To explore the effect of baicalin on human nucleus pulposus cells (NPCs) in response to interleukin (IL)-1ß stimulation. METHODS: Viability of NPCs was measured by cell counting kit-8 (CCK-8) assay. TUNEL staining assay and flow cytometry were performed to detect apoptotic cell death of NPCs. Western blot analysis was conducted to detect the expression levels of proteins. Enzyme-linked immunosorbent assay (ELISA) was applied for the determination of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), and IL-6. Oxidative stress indicators including reactive oxygen species (ROS) production, malondialdehyde (MDA) level, and superoxide dismutase (SOD) activity were measured. RESULTS: Baicalin attenuated IL-1ß-caused cell viability reduction and apoptosis in NPCs. IL-1ß-induced increase in Bax expression and decrease in Bcl-2 expression were attenuated by baicalin treatment. IL-1ß-induced production of iNOS, COX-2, IL-6, and TNF-α in NPCs was inhibited by baicalin treatment. Baicalin treatment reversed IL-1ß-induced increase in ROS production and MDA level, as well as decrease in SOD activity. Furthermore, baicalin treatment elevated the expression levels of Col II and Aggrecan and downregulated the expression levels of MMP3, MMP13, and ADAMTS5 in IL-1ß-induced NPCs. A total of 402 related targets of baicalin and 134 related targets of intervertebral disk degeneration were found, and nine intersection targets were screened out. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that mitogen-activated protein kinase (MAPK) pathway was found to be involved in the effects of baicalin. CONCLUSIONS: Baicalin exhibited protective effects on IL-1ß-caused cell viability reduction, apoptosis, oxidative stress, inflammation, and extracellular matrix degradation in NPCs. In addition, we found c-Jun N-terminal kinase (JNK) and p38 MAPK pathways as targets of baicalin through bioinformatic analysis.

Emodin protects against apoptosis and inflammation by regulating reactive oxygen species-mediated NF-κB signaling in interleukin-1ß-stimulated human nucleus pulposus cells.

Intervertebral disc degeneration (IDD) is a complex degradative disorder associated with inflammation. Emodin, an anthraquinone derivative, possesses strong anti-inflammatory activity. This study focused on the in vitro therapeutic action of emodin in a cellular model of IDD. Human nucleus pulposus cells (NPCs) were stimulated with interleukin-1ß (IL-1ß) to induce inflammation. Cell Counting Kit-8 and terminal deoxynucleotidyl transferase dUTP nick end labeling staining assays were performed to evaluate the viability and apoptosis of NPCs, respectively. Caspase-3 activity was measured to indirectly assess cell apoptosis. Western blot analysis was performed to detect protein expression levels. Reverse transcription-polymerase chain reaction was performed for the detection of relative mRNA levels of tumor necrosis factor-α (TNF-α) and IL-6. Enzyme-linked immunosorbent assay was performed to analyze TNF-α and IL-6 secretion. Our results showed that emodin treatment mitigated IL-1ß-induced reduction of cell viability in NPCs. Moreover, the increase in reactive oxygen species (ROS) production, apoptotic rate, and caspase-3 activity in IL-1ß-stimulated NPCs was reduced by emodin treatment. Treatment with emodin also abolished IL-1ß-induced inflammation in NPCs, as indicated by reduced secretion of IL-6 and TNF-α. Besides, the increase in expression levels of phosphorylated p65 and nuclear p65 in IL-1ß-stimulated NPCs was suppressed by emodin treatment. Furthermore, inhibition of nuclear factor kappa B (NF-κB) activation with pyrrolidine dithiocarbamate aggravated the protective effects of emodin. These results suggested that emodin protected NPCs against IL-1ß-induced apoptosis and inflammation via inhibiting ROS-mediated activation of NF-κB.

Cyanidin attenuates the apoptosis of rat nucleus pulposus cells and the degeneration of intervertebral disc via the JAK2/STAT3 signal pathway in vitro and in vivo.

CONTEXT: Cyanidin has been shown to have therapeutic potential in osteoarthritis. However, it is unclear whether cyanidin prevents the progression of intervertebral disc degeneration (IVDD). OBJECTIVE: This study evaluates the effects of cyanidin on IVDD in vitro and in vivo. MATERIALS AND METHODS: Nucleus pulposus cells (NPCs) isolated from lumbar IVD of 4-week-old male Sprague-Dawley (SD) rats were exposed to 20 ng/mL IL-1ß, and then treated with different doses (0-120 µM) of cyanidin for 24 h. SD rats were classified into three groups (n = 8) and treated as follows: control (normal saline), IVDD (vehicle), IVDD + cyanidin (50 mg/kg). Cyanidin was administered intraperitoneally for 8 weeks. RESULTS: The IC50 of cyanidin for NPCs was 94.78 µM, and cyanidin had no toxicity at concentrations up to 500 mg/kg in SD rats. Cyanidin inhibited the apoptosis of NPCs induced by IL-1ß (12.73 ± 0.61% vs. 18.54 ± 0.60%), promoted collagen II (0.82-fold) and aggrecan (0.81-fold) expression, while reducing MMP-13 (1.02-fold) and ADAMTS-5 (1.40-fold) expression. Cyanidin increased the formation of autophagosomes in IL-1ß-induced NPCs, and promoted LC3II/LC3I (0.83-fold) and beclin-1 (0.85-fold) expression, which could be reversed by chloroquine. Cyanidin inhibited the phosphorylation of JAK2 (0.47-fold) and STAT3 (0.53-fold) in IL-1ß-induced NPCs. The effects of cyanidin could be enhanced by AG490. Furthermore, cyanidin mitigated disc degeneration in IVDD rats in vivo. DISCUSSION AND CONCLUSIONS: Cyanidin improved the function of NPCs in IVDD by regulating the JAK2/STAT3 pathway, which may provide a novel alternative strategy for IVDD. The mechanism of cyanidin improving IVDD still needs further work for in-depth investigation.

Cyanidin-3-glucoside protects against high glucose-induced injury in human nucleus pulposus cells by regulating the Nrf2/HO-1 signaling.

Cyanidin-3-glucoside (C3G) is a well-known natural anthocyanin with antioxidant and anti-inflammatory properties. In this study, we explored the role and action mechanism of C3G in high glucose (HG)-induced damage of human nucleus pulposus cells (HNPCs). Cell viability was assessed by CCK-8 assay. TUNEL assay was performed for detecting apoptotic rate. Western blot was performed to determine the expression levels of cl-caspase-3, caspase-3, Bax, Bim, collagen II, aggrecan, MMP-3, MMP-13, and ADAMTS5. Reactive oxygen species (ROS) generation was analyzed using DCFH-DA staining. The Nrf2 was knocked down or overexpressed in HNPCs through transfection with si-Nrf2 or pcDNA3.0-Nrf2. C3G treatment (12.5, 25, and 50 µM) improved cell viability of HNPCs under HG condition. HG-induced cell apoptosis of HNPCs was attenuated by C3G with decreased apoptotic rate and relative levels of cl-caspase-3/caspase-3, Bax, and Bim. C3G treatment caused significant increase in expression levels of collagen II and aggrecan and decrease in the relative levels of MMP-3, MMP-13, and ADAMTS5. After treatment with C3G, ROS generation in HNPCs was markedly reduced. Treatment with N-acetylcysteine (NAC) reversed HG-induced cell apoptosis and extracellular matrix (ECM) degradation. C3G treatment induced the expression of Nrf2 and HO-1 in HG-induced HNPCs. Moreover, knockdown of Nrf2 reversed the inhibitory effect of C3G on ROS production. Summarily, C3G exerted a protective effect on ROS-mediated cellular damage in HNPCs under HG condition, which was attributed to the induction of the Nrf2/HO-1 signaling pathway.

Higenamine mitigates interleukin-1ß-induced human nucleus pulposus cell apoptosis by ROS-mediated PI3K/Akt signaling.

Intervertebral disc degeneration (IDD) is a natural problem linked to the inflammation. Higenamine exerts multiple pharmacological properties in inflammation-related disorders. Our study aimed to explore the function of higenamine on interleukin (IL)-1ß-caused apoptosis of human nucleus pulposus cells (HNPCs). Cell apoptosis was investigated by TUNEL and flow cytometry. Apoptosis-related biomarkers were determined by qRT-PCR or Western blotting. The protein in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling was measured by Western blotting. We found that higenamine showed little effect on cell apoptosis, but mitigated IL-1ß-caused apoptosis in a dose-dependent pattern. Higenamine attenuated IL-1ß-induced decrease of Bcl-2 and increase of Bax and cleaved caspase-3. Higenamine did not affect the reactive oxygen species (ROS) level and the PI3K/Akt signaling, but attenuated IL-1ß-induced ROS production and inhibition of the PI3K/Akt signaling. IL-1ß repressed the activation of the PI3K/Akt pathway, but ROS inhibition using N-acetylcysteine (NAC) rescued this pathway. The PI3K/Akt signaling suppression using LY294002 reversed the inhibitive effect of higenamine on IL-1ß-caused apoptosis, and this effect was weakened by ROS inhibition. In conclusion, higenamine attenuates IL-1ß-caused apoptosis of HNPCs via ROS-mediated PI3K/Akt pathway.

Liraglutide Protects Nucleus Pulposus Cells Against High-Glucose Induced Apoptosis by Activating PI3K/Akt/ mTOR/Caspase-3 and PI3K/Akt/GSK3ß/Caspase-3 Signaling Pathways.

Background and Objective: Diabetes mellitus (DM) is reportedly a significant risk factor for intervertebral disc degeneration (IDD). Incretin system and particularly glucagon-like peptide 1 (GLP-1) because of its glucose-lowering effects has become an important target in therapeutic strategies of type 2 diabetes (T2D). Liraglutide is a GLP-1 receptor (GLP-1R) agonist with glucoregulatory and insulinotropic functions as well as regulatory functions on cell proliferation, differentiation, and apoptosis. However, little is known on the roles and signaling pathways of apoptosis protecting effects of liraglutide in IDD. This study aimed to investigate the potential protective effects of liraglutide against high glucose-induced apoptosis of nucleus pulposus cells (NPCs) and the possible involved signaling pathways. Methods: The human NPCs were incubated with 100 nM liraglutide alone or in combination with LY294002 (PI3K inhibitor), rapamycin (mTOR inhibitor), and SB216763 (GSK3ß inhibitor) in a high glucose culture for 48 h. The four groups were assessed further for apoptosis and genes expressions. The apoptotic effect was evaluated by flow cytometry and further confirmed by cell death detection enzyme-linked immunoassay plus (ELISAPLUS). The gene and protein expression levels were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting techniques. The results were comparatively assessed between the four groups. Results: The results confirmed the presence of GLP-1R in the NPCs indicating that liraglutide inhibited the high glucose-induced apoptosis, which was blocked by silencing GLP-1R with siRNA. Moreover, liraglutide stimulated the phosphorylation of Akt, mTOR and GSK3ß. Treatment with LY294002 significantly increased the apoptosis of NPCs and reduced the levels of their downstream substrates (p-AKT, p-mTOR, and p-GSK3ß). Further assessments revealed that activation of mTOR and GSK3ß was almost completely inhibited by rapamycin and SB216763, respectively, which significantly increased the caspase-3 levels. Conclusion: Liraglutide could protect NPCs against high glucose-induced apoptosis by activating the PI3K/AKT/mTOR/caspase-3 and PI3K/AKT/GSK3ß/caspase-3 signaling pathways.

Percutaneous endoscopic lumbar discectomy compared with other surgeries for lumbar disc herniation: A meta-analysis.

OBJECTIVE: This meta-analysis was performed to investigate whether percutaneous endoscopic lumbar discectomy (PELD) had a superior effect than other surgeries in the treatment of patients with lumbar disc herniation (LDH). METHOD: We searched PubMed, Embase, and Web of Science through February 2018 to identify eligible studies that compared the effects and complications between PELD and other surgical interventions in LDH. The outcomes included success rate, recurrence rate, complication rate, operation time, hospital stay, blood loss, visual analog scale (VAS) score for back pain and leg pain, 12-item Short Form Health Survey (SF12) physical component score, mental component score, Japanese Orthopaedic Association Score, Oswestry Disability Index. A random-effects or fixed-effects model was used to pool the estimate, according to the heterogeneity among the included studies. RESULTS: Fourteen studies (involving 2,528 patients) were included in this meta-analysis. Compared with other surgeries, PELD had favorable clinical outcomes for LDH, including shorter operation time (weight mean difference, WMD=-18.14 minutes, 95%CI: -25.24, -11.05; P < .001) and hospital stay (WMD = -2.59 days, 95%CI: -3.87, -1.31; P < .001), less blood loss (WMD = -30.14 ml, 95%CI: -43.16, -17.13; P < .001), and improved SF12- mental component score (WMD = 2.28, 95%CI: 0.50, 4.06; P = .012)) and SF12- physical component score (WMD = 1.04, 95%CI: 0.37, 1.71; P = .02). However, it also was associated with a significantly higher rate of recurrent disc herniation (relative risk [RR] = 1.65, 95%CI: 1.08, 2.52; P = .021). There were no significant differences between the PELD group and other surgical group in terms of success rate (RR = 1.01, 95%CI: 0.97, 1.04; P = .733), complication rate (RR = 0.86, 95%CI: 0.63, 1.18; P = .361), Japanese Orthopaedic Association Score score (WMD = 0.19, 95%CI: -1.90, 2.27; P = .861), visual analog scale score for back pain (WMD = -0.17, 95%CI: -0.55, 0.21; P = .384) and leg pain (WMD = 0.00, 95%CI: -0.10, 0.10; P = .991), and Oswestry Disability Index score (WMD = -0.29, 95%CI: -1.00, 0.43; P = .434). CONCLUSION: PELD was associated with better effects and similar complications with other surgeries in LDH. However, it also resulted in a higher recurrence rate. Considering the potential limitations in the present study, further large-scale, well-performed randomized trials are needed to verify our findings.

Resveratrol Combined with 17ß-Estradiol Prevents IL-1ß Induced Apoptosis in Human Nucleus Pulposus Via The PI3K/AKT/Mtor and PI3K/AKT/GSK-3ß Pathway.

BACKGROUNDS: Nucleus pulposus (NP) apoptosis is mainly charged for the pathological process of Intervertebral disc degeneration (IVDD). Our previous study revealed that Resveratrol (RSV) combined with 17ß-estradiol (E2) was more effective in cutting down IL-1ß induced NP cell apoptosis via PI3K/AKT pathway. The present study further evaluated the effect of RSV and E2 in the anti-apoptosis process of IVDD. METHODS: Human nucleus pulposus (NP) cells culture system and IL-1ß inducing apoptosis model were constructed in this research. RSV and E2 were used to inhibit apoptosis. FACS (Fluorescence-activated cell sorting) and CCK-8 (Cell Counting Kit-8) assays were respectively used to determine apoptotic incidence and cell viability of NP cells. Quantitative RT-PCR was used to determine expression of target genes in mRNA level, and western blot analysis was performed to detect the changes of related protein expression. RESULTS: RSV combined with E2 attenuated IL-1ß-induced cell apoptosis and recovered cell viability. Blockers for mTOR and GSK-3ß abated the effect of RSV and E2. RSV combined with E2 obviously increased activated P-mTOR and P-GSK-3ß, which contributes to the downregulation of caspase-3. Activated P-NF-kappa B was not involved in the anti-apoptosis process of RSV and E2. CONCLUSION: Combination of Resveratrol and 17ß-estradiol efficiently resisted IL-1ß induced apoptosis of NP cell, mainly through PI3K/AKT/mTOR/caspase-3 and PI3K/AKT/GSK-3ß pathway.

Upregulation of Sirt1 by tyrosol suppresses apoptosis and inflammation and modulates extracellular matrix remodeling in interleukin-1ß-stimulated human nucleus pulposus cells through activation of PI3K/Akt pathway.

Intervertebral disc degeneration (IDD) is the major pathogenesis of lower back pain. Tyrosol is a polyphenolic compound that exhibits anti-oxidant, anti-apoptotic, and anti-inflammatory effects. Herein, we explored the effects and mechanisms of tyrosol on IDD progression in interleukin (IL)-1ß-stimulated human nucleus pulposus cells (HNPCs). Cell viability and apoptosis were detected by CCK-8 and flow cytometry analysis, respectively. The production of tumor necrosis factor-α (TNF-α), IL-6, nitric oxide (NO), and prostaglandin E2 (PGE2) was examined to evaluate inflammation. The mRNA expression of matrix metalloproteinases (MMPs) (MMP-3/9/13), collagen type II, SRY-related high mobility group box 9 (SOX-9), and aggrecan was measured by qRT-PCR. Protein levels of silent information regulator 2 homolog 1 (Sirt1), phosphorylated protein kinase B (p-Akt), Akt, collagen type II, SOX-9, and aggrecan were determined by western blot. Results showed that tyrosol attenuated IL-1ß-induced viability reduction, apoptosis, and caspase-3/7 activity in HNPCs. The increase in the production of TNF-α, IL-6, NO, and PGE2 in IL-1ß-treated HNPCs was abolished by tyrosol treatment. Tyrosol treatment reversed IL-1ß-induced upregulation of MMP-3, MMP-9, and MMP-13, and downregulation of collagen II, SOX-9, and aggrecan in HNPCs. Additionally, tyrosol treatment activated the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in IL-1ß-stimulated HNPCs. Sirt1 was upregulated by tyrosol, and Sirt1 silencing inhibited Akt phosphorylation in HNPCs. Sirt1 knockdown attenuated the effects of tyrosol on IL-1ß-induced apoptosis, inflammation, and ECM remodeling in HNPCs. In summary, upregulation of Sirt1 by tyrosol suppressed apoptosis and inflammation and regulated ECM remodeling in IL-1ß-stimulated HNPCs through activation of PI3K/Akt pathway.

Resveratrol protects against apoptosis induced by interleukin-1ß in nucleus pulposus cells via activating mTOR/caspase-3 and GSK-3ß/caspase-3 pathways.

OBJECTIVE: The purpose of the present study was to investigate the specific downstream signaling pathway mediated by PI3K/Akt in resveratrol (RES) anti-apoptosis of nucleus pulposus cells (NPCs). MATERIALS AND METHODS: Human NPCs were cultured and divided into six groups. Interleukin (IL)-1ß was used to induce apoptosis and RES to inhibit apoptosis. Fluorescence-activated cell sorting (FACS) analysis was used to test apoptotic incidence of NPCs, cell counting kit-8 (CCK-8) assay was performed to detect cell viability, The expression level of caspase-3 mRNA was detected by RT-qPCR, and protein levels were determined by Western blot. RESULTS: Flow cytometry analysis showed that IL-1ß increased the apoptosis rate of NPCs in each group, and RES significantly decreased the apoptosis rate, while rapamycin (RAPA) and SB216763 inhibited the effect of RES and increased the apoptosis rate again. Similarly, CCK-8 showed that IL-1ß decreased activity of NPCs in each group, while RES increased cell activity, RAPA and SB216763 inhibited the effect of RES and decreased cell activity. RT-qPCR results showed IL-1ß significantly increased the level of caspase-3 expression, but it was significantly decreased by using RES, RAPA and SB216763 respectively attenuated effects of RES. Western blot results showed that activated caspase-3 was inhibited by RES effect, and was up-regulated again after the addition of RAPA and SB216763. In addition, p-mTOR and p-GSK-3ß were up-regulated by RES and down-regulated by RAPA and SB216763. CONCLUSION: RES can inhibit apoptosis induced by IL-1ß in human NPCs. PI3K/Akt/mTOR/caspase-3 and PI3K/Akt/GSK-3ß/caspase-3 pathways are potential mechanisms underlying this process.

Higenamine inhibits IL-1ß-induced inflammation in human nucleus pulposus cells.

Intervertebral disc degeneration (IDD) is a natural progression of the aging process associated with inflammation. Higenamine, a plant-based alkaloid, has been identified to possess various pharmacological properties, including anti-inflammatory activity. In the present study, we aimed to evaluate the role of higenamine in interleukin (IL)-1ß-induced inflammation in human nucleus pulposus cells (NPCs). The results showed that higenamine improved cell viability in IL-1ß-induced NPCs. The IL-1ß-dependent up-regulation of inflammatory molecules including inducible nitric oxide synthase (iNOS), nitric oxide (NO), prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), and IL-6 was attenuated by higenamine in NPCs. The increased productions of matrix metalloproteinases (MMP-3 and MMP-13), as well as a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS-4 and ADAMTS-5) were significantly mitigated by higenamine treatment. Furthermore, we also found that higenamine suppressed the IL-1ß-induced activation of NF-κB signaling pathway in NPCs. In conclusion, the present study proved that higenamine exhibited anti-inflammatory activity against IL-1ß-induced inflammation in NPCs via inhibiting NF-κB signaling pathway. These results suggested that higenamine might be a therapeutic agent for the treatment of IDD.

Kyphoplasty for chronic painful osteoporotic vertebral compression fractures via unipedicular versus bipedicular approachment: a comparative study in early stage.

BACKGROUND: Osteoporotic compression fractures (OVCFs) commonly occur in aged people, and as much as one-third of these fractures progress to chronic pain. Kyphoplasty (KP) is proved to be efficacious for pain relief and vertebral height restoration in chronic OVCFs, but there is still no data available about the clinical and radiographical outcomes compared by unipedicular and bipedicular KP in treating chronic painful OVCFs. PURPOSE: To assess the clinical and radiographical outcomes in treating chronic painful OVCFs compared by unipedicular and bipedicular KP. METHODS: Fifty-eight patients with a total of sixty-six chronic painful OVCFs were enroled in our study. They were randomly allocated into two groups: group I (n=33) was treated with unipedicular KP and group II (n=25) with bipedicular KP. The operation times for each group were recorded and compared. Preoperative and postoperative of visual analogue scores (VAS) and oswestry disability index (ODI) scores were compared 2 weeks after surgery within each group and between groups. The radiographic outcomes were evaluated by the restoration rate (RR) in the most compressed point of the vertebral bodies. RESULTS: Significant improvement on the VAS, ODI scores and RR was noted in each group (p<0.001), and there is no significant difference existing in clinical outcomes between the two groups. The mean operation time for each vertebra in group I was significantly shorter than in group II (p<0.001). But the RR in group II was higher than in group I (p=0.041). CONCLUSION: Both unipedicular kyphoplasty and bipedicular kyphoplasty can achieve satisfactory clinical and radiographic outcomes in treating the chronic painful OVCFs and the operation time is shorter in unipedicular kyphoplasty. However, the bipedicular kyphoplasty is more efficacious in height restoration.