Polyphenols as Potential Antioxidants for the Treatment of Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IDD) is a common musculoskeletal system disease, which is one of the most important causes of low back pain. Despite the high prevalence of IDD, current treatments are limited to relieving symptoms, and there are no effective therapeutic agents that can block or reverse the progression of IDD. Oxidative stress, the result of an imbalance between the production of reactive oxygen species (ROS) and clearance by the antioxidant defense system, plays an important role in the progression of IDD. Polyphenols are antioxidant compounds that can inhibit ROS production, which can scavenge free radicals, reduce hydrogen peroxide production, and inhibit lipid oxidation in nucleus pulposus (NP) cells and IDD animal models. In this review, we discussed the antioxidant effects of polyphenols and their regulatory role in different molecular pathways associated with the pathogenesis of IDD, as well as the limitations and future prospects of polyphenols as a potential treatment of IDD.

Tanshinone IIA is superior to paricalcitol in ameliorating tubulointerstitial fibrosis through regulation of VDR/Wnt/ß-catenin pathway in rats with diabetic nephropathy.

Glomerulosclerosis and tubulointerstitial fibrosis (TIF) are closely involved in the development of diabetic nephropathy (DN). Moreover, the development of TIF is closely related to epithelial-to-mesenchymal transition (EMT). Tanshinone IIA (Tan) has various pharmacological effects, especially the anti-fibrotic effect. And it is mainly used in the clinical treatment of cardiovascular diseases. Currently, the protective effect of Tan on DN and its possible mechanism have not been clearly elucidated. Our previous studies illustrated that Tan could improve the EMT of HK-2 cells induced by high glucose by regulating the vitamin D receptor (VDR)/Wnt/ß-catenin pathway. Here, we collected demographic information and laboratory results from the National Health and Nutrition Examination Survey (NHANES) database in order to investigate the relationship between VD and DN. Then, we established a DN model and treated DN rats with Tan and paricalcitol (Par) for 6 weeks. We subsequently compared the changes in general condition, renal function, pathological changes, and TIF-related protein expression levels of control rats, DN rats induced by STZ, DN rats with Tan at 5.4 mg/kg, DN rats with Tan at 10.8 mg/kg, and DN rats with Par at 0.054 µg/kg, to explore the effect and mechanism of Tan and Par on DN rats. The results showed that VD had a protective effect against DN in diabetic patients. And we found that Tan had a protective effect on renal fibrosis in DN rats, which was superior to Par in improving the symptoms of "three more and one less," reducing fasting blood glucose level, improving renal index, BUN/SCr, and UACR, reducing histopathological damage of kidney, and improving the expression of fibrosis-related proteins in kidney tissue by regulating VDR/Wnt/ß-catenin pathway. Tan was superior to Par in ameliorating tubulointerstitial fibrosis by regulating VDR/Wnt/ß-catenin pathway in rats with diabetic nephropathy.

[Accumulation Characteristics, Sources, and Health Risks of Soil Lead of Urban Parks in Beijing].

Urban parks have multiple functions such as social culture, economy, and environmental services during urban development. The rapid development of cities and economy may lead to the accumulation of heavy metals in the soil of urban parks, which may threaten human health. A total of 140 soil samples were collected in 32 typical parks in Beijing. The accumulation characteristics of Pb in the soil of urban parks were analyzed using the single-factor pollution and geo-accumulation indices. The sources of Pb pollution in soils were quantitatively analyzed using the stable isotope of Pb, and the health risk was assessed using the probabilistic risk assessment method based on Monte Carlo simulation. The results showed that the geometric mean of Pb in soils of urban parks in Beijing was 38.63 mg·kg-1, which was 1.48 times the background value. However, it did not exceed the risk screening value(GB 36600-2018). The accumulation of soil Pb in urban parks increased with the increase in the proximity between the park and the central urban area and the increase in the establishment time. The soil Pb pollution index of 2 ring, 2-4 ring, and 4-6 ring parks were 0.16, 0.10, and 0.09, which did not reach the pollution level, and the geo-accumulation indices were 0.80, 0.07, and -0.31, respectively. Except for the no-moderate pollution level in ring 2 and ring 2 to ring 4, the other rings did not reach the pollution level. The sources of Pb pollution in urban parks were coal combustion, road dust, and paint, with the contributions of 45.4%, 19.6%, and 13.9%, respectively. The 95% quantiles of hazard index(HI) of soil Pb in the park for different age groups were 1.11E-01, 8.57E-02, 6.39E-02, 1.64E-02, 1.36E-02, 1.26E-02, 1.64E-02, and 1.78E-02, respectively, which indicated that there was no potential non-carcinogenic risk(HI<1). Exposure duration was the most sensitive to non-carcinogenic risks in people aged 0-18 years, and soil Pb concentration was the most sensitive to non-carcinogenic risks in people aged 18-80 years. The increase in body weight often reduced the non-carcinogenic risks. These results can provide theoretical basis for soil environmental risk control in urban parks.

Scientific Bibliometric and Visual Analysis of Studies on Autophagy in Intervertebral Disc Degeneration Based on Web of Science.

OBJECTIVE: To analyze the current research trends and potential mechanisms related to the role of autophagy in intervertebral disc degeneration (IVDD) and to provide new ideas for future research in this field. METHODS: All articles on IVDD and autophagy were retrieved and extracted from the Web of Science (WoS) core collection database. The results were evaluated and visualized using the bibliometric Web site, CiteSpace, and VOSviewer software, including annual articles published, countries, institutions, authors, journals, research areas, funding agencies, citations, and keywords. RESULTS: From January 1, 2011, to December 31, 2022, 323 reviews and original articles were included, and the overall trend in the number of articles was increasing rapidly. China and the United States were the countries with the most scientific research achievements. The 323 articles received a total number of citations of 6949, with an H index of 43 and an average citation of 21.51. The top publication country, institution, author, journal, research area, and funding agency were China, Huazhong University of Science and Technology, Cao Yang of Tongji Medical College, Oxidative Medicine and Cellular Longevity, cell biology, and National Natural Science Foundation of China, respectively. Most of the keywords were associated with the mechanisms and regulatory networks of autophagy. In addition, with increasing evidence showing the key role of autophagy in IVDD, therapy, signaling pathway, and mitophagy are emerging as new research hot spots that should be paid more attention. CONCLUSIONS: This study provided a scientific perspective on autophagy in IVDD and elucidated the current research status and hot spots in this field. The mechanism of autophagy and the application of regulating autophagy in the treatment of IVDD deserve further research.

Evaluation of chickpea protein isolate as a partial replacement for phosphate in pork meat batters: Techno-functional properties and molecular characteristic modifications.

The effects of chickpea protein isolate (CPI, 0.5-2 %, w/w) on the techno-functional properties of 50 % reduced-phosphate pork meat batters (RPMBs) were explored. The results showed that 1.5-2 % CPI significantly decreased the cooking loss but significantly increased the emulsion stability, hardness, gumminess, chewiness and yellowness (b*) of RPMBs (P < 0.05). CPI altered molecular characteristics of RPMBs, as demonstrated by the increased storage modulus (G'), the conversion of free water into immobilized water, the reduced intensities of the aliphatic residue Raman bands, the decreased α-helical structure and the formation of well-organized gel networks with evenly distributed small fat globules. Principal component analysis and Pearson's correlation analysis indicated that CPI-induced changes in RPMB techno-functional properties were closely related to molecular characteristics. Hierarchical cluster analysis suggested that RPMBs supplemented with 1.5-2 % CPI were highly similar in techno-functional properties to the high-phosphate group. Therefore, CPI may potentially be used to develop reduced-phosphate meat products.

Which Criterion for Wound Drain Removal is Better Following Posterior 1-Level or 2-Level Lumbar Fusion With Instrumentation: Time Driven or Output Driven?

STUDY DESIGN: Case-control study. OBJECTIVES: To compare the outcomes of 2 different criteria (time driven and output driven) for wound drain removal and identify which one is better. METHODS: 743 patients who underwent posterior lumbar fusion with instrumentation involving 1 or 2 motion segments were enrolled in this study. Based on the different criteria for drain removal, the patients were divided into 2 groups. The drains were discontinued by time driven (postoperative day 2) in group I and output driven (<50 ml per day) in group II. Demographic characteristics, perioperative parameters and clinical outcomes were compared between the 2 groups. RESULTS: The demographic characteristics in both groups were comparable. The postoperative drain output, total blood loss, postoperative timing of ambulation, and postoperative duration of hospital stay in group I were lower than those in group II (P < 0.001). There was a higher proportion of patients requiring postoperative blood transfusion in group II, but not to a level of statistical significance (P = 0.054). There was no statistical significant difference in the incidence of surgical site infection (SSI) or symptomatic spinal epidural hematoma (SEH) between the 2 groups (P > 0.05). CONCLUSIONS: This study reveals that there are more benefits of wound drain removal by time driven than that by output driven for patients undergoing posterior 1-level or 2-level lumbar fusion with instrumentation, including less postoperative drain output, less total blood loss, earlier postoperative timing of ambulation and less postoperative duration of hospital stay without increasing the incidence of postoperative SSI or symptomatic SEH.

[Pollution Characteristics and Source Apportionment of Atmospheric Volatile Organic Compounds in Summer in Yuncheng City].

Based on the online monitoring data of VOCs, O3, and NO2 in Yuncheng City from June to August 2020, the pollution characteristics of VOCs in Yuncheng City in summer were analyzed. At the same time, the main emission sources were determined using a PMF model, and the chemical reactivity of VOCs was evaluated using the maximum incremental reactivity (MIR) method and fractional aerosol coefficients (FAC). The results showed that the urban area of Yuncheng was seriously polluted by VOCs and NO2 in the early morning and evening during summer, the peak value of VOCs daily variation occurred at 08:00 and 20:00, respectively, and was mainly affected by the morning and evening peaks in traffic. The ρ(VOCs) from June to August was 50.52 µg·m-3, and the species with the highest proportion were alkanes (39.39%) and oxygenated volatile organic compounds (OVOCs, 34.63%). Five VOCs emission sources were determined by the PMF model, of which the largest contribution was from motor vehicle exhaust emission sources (33.10%), followed by industrial emission sources (29.46%), natural gas and coal combustion sources (17.31%), solvent use sources (11.94%), and plant emission sources (8.19%). Controlling motor vehicle exhaust emission sources is the key to alleviate VOCs pollution in summer in Yuncheng City. The average ozone formation potential (OFP) of VOCs was 162.88 µg·m-3, in which OVOCs had the highest contribution rate (45.37%); acetaldehyde, propionaldehyde, ethylene, isoprene, and toluene were the key active components; and industrial emission sources were the emission sources with the highest contribution rate. The average value of secondary organic aerosol formation potential (SOAp) of VOCs was 0.40 µg·m-3, in which the contribution rate of aromatic hydrocarbons was the highest (88.00%), and the solvent use source was the emission source with the highest contribution rate.

The Mini-Open Wiltse Approach with Pedicle Screw Fixation Versus Percutaneous Pedicle Screw Fixation for Treatment of Neurologically Intact Thoracolumbar Fractures: A Systematic Review and Meta-Analysis.

OBJECTIVE: The purpose of the present study was to compare the clinical outcomes and complications between the mini-open Wiltse approach with pedicle screw fixation (MWPSF) and percutaneous pedicle screw fixation (PPSF) in treating neurologically intact thoracolumbar fractures. METHODS: We comprehensively searched PubMed, Web of Science, Embase, and the Cochrane Library and performed a systematic review and meta-analysis of all randomized controlled trials and retrospective comparative studies assessing these important indexes of the 2 methods using Review Manager, version 5.4. The clinical outcomes are presented as the risk difference for dichotomous outcomes and the mean difference for continuous outcomes with the 95% confidence intervals. Heterogeneity was assessed using the χ2 test and I2 statistics. The study was registered with PROSPERO (CRD 42021290078). RESULTS: Two randomized controlled trials and six retrospective cohort studies were included in the present analysis. The percutaneous approach was associated with less intraoperative blood loss compared with the mini-open Wiltse approach. No significant differences were found in the total length of the incisions, hospitalization time, postoperative visual analog scale scores, postoperative Oswestry disability index, postoperative Cobb angle, postoperative Cobb angle correction, postoperative Cobb angle correction loss, accuracy rate of pedicle screw placement, and postoperative complications between MWPSF and PPSF. However, the incidence of facet joint violation was significantly higher in the PPSF group. In addition, MWPSF was associated with a shorter operative time, shorter intraoperative fluoroscopy time, lower hospitalization costs, better postoperative vertebral body angle and percentage of vertebral body height compared with PPSF. CONCLUSIONS: Both MWPSF and PPSF are safe and effective treatments of neurologically intact thoracolumbar fractures. Nevertheless, our results have indicated that MWPSF might be the better choice, because it has a shorter learning curve and decreased facet joint violation, operative time, hospitalization costs, and radiation exposure. In addition, MWPSF was associated with better improvement of the postoperative vertebral body angle and percentage of vertebral body height.

Parkin-mediated mitophagy protects against TNF-α-induced stress in bone marrow mesenchymal stem cells.

Bone marrow mesenchymal stem cells (BMSCs) have been investigated as cellular therapeutics for intervertebral disc degeneration. However, transplanted BMSCs are prone to be damaged. TNF-α is reported to extensively promote degeneration process. Nevertheless, the relationship between BMSCs senescence and TNF-α-induced stress has not been elucidated. Previous studies showed that mitophagy is a crucial factor in maintaining cellular homeostasis. Hence, we sought to clarify the role and mechanism of mitophagy in TNF-α-induced biological changes of BMSCs. Here, we found that TNF-α caused transient senescent damage in the early stage. Meanwhile, Parkin-mediated mitophagy was initiated and weakened the damage through maintaining mitochondria homeostasis. After inhibiting mitophagy by knockdown of Parkin, TNF-α irreversibly caused cellular senescence. These results suggested that Parkin-mediated mitophagy played protective role in BMSCs in response to TNF-α, which could be a crucial therapeutic target in the future.

[Spatiotemporal Distribution and Seasonal Characteristics of Regional Transport of PM2.5 in Yuncheng City].

The spatiotemporal distribution characteristics of PM2.5 pollution in Yuncheng City were analyzed based on the ambient air quality monitoring data from March 2019 to February 2020, and the hybrid single-particle Lagrangian integrated trajectory (HYSPLIT) and cluster analysis were used to discuss the contamination transportation pathway and the distribution of potential pollution sources affecting PM2.5 in Yuncheng City in different seasons. The results showed that the PM2.5 concentration in Yuncheng was the highest in winter (111.24 µg·m-3) and the lowest in summer (30.02 µg·m-3). PM2.5/PM10 was greater than 0.6 in autumn and winter, indicating that the particulate matter pollution in Yuncheng City in autumn and winter was mainly fine particulate matter; spatially, the annual mean value of PM2.5 presented distribution characteristics that were high in the northern and central regions and low in the eastern and western regions. The high-value areas of PM2.5 were significantly and strongly correlated with SO2, NO2, and CO, indicating that local emissions contributed to the high values. The highest values in spring and winter were located in Hejin City (58.50 µg·m-3) and Jishan County (142.33 µg·m-3), and the highest values in summer and autumn were located in Pinglu County (36.92 µg·m-3) and the Salt Lake area (62.94 µg·m-3), respectively. Transportation analysis showed that spring and winter were mainly affected by air masses transporting northwestward, accounting for 58.69% and 55.77%. In summer, air masses were mainly eastward and southward, and in autumn, pollution was from short-distance transport air masses from southwestern Henan. The largest ratio was 32.89%; the potential source area was the smallest in spring and summer; it then began to grow in autumn, and it was the widest in the winter and had the highest contribution. The main source area in spring and summer was located in western and central Henan, and in autumn and winter, source areas were concentrated at the junction of Shaanxi, Shanxi, and Henan and west of Shaanxi.

Complications and outcomes of open posterior lumbar spinal fusion surgery in obese patients: a meta-analysis.

OBJECTIVE: The aim of this study was to determine whether obesity affects the operation, complications and outcomes after open posterior lumbar spinal fusion surgery for the treatment of low back pain and leg pain. METHODS: A meta-analysis of studies that compared the outcome of posterior lumbar spinal fusion in obese and non-obese patients. A total of 16 studies were included. RESULTS: There was no difference in pain and functional outcomes. Posterior lumbar spinal fusion in obese patients resulted in a statistically significant increase in intra-operative blood loss (weighted mean difference 40.93, 95% confidence interval (CI) 15.97-65.90, n = 243, and p=.001), longer duration of surgery (weighted mean difference -1.64, 95% CI -4.12 to 0.84, n = 1460, and p=.19), more complications (odds ratio: 1.59, 95% CI 1.24-2.05, n = 339, and p<.001) and extend length of stay (weighted mean difference 0.31, 95% CI 0.07-0.55, n = 1408, and p=.01). CONCLUSIONS: Obese patients experience more blood loss, longer duration of surgery, more complications and extended length of stay, but their back and leg pain and functional outcomes are similar to non-obese patients. Based on these results, obesity is not a contraindication to open posterior lumbar spinal fusion surgery.

Mitophagy is a protective response against oxidative damage in bone marrow mesenchymal stem cells.

AIMS: Bone marrow mesenchymal stem cells (BMSCs) show great potential in clinical applications such as in intervertebral disc degeneration. Nevertheless, environmental stress during the BMSC transplant or in the injured tissues is a catastrophic factor that causes cell toxicity and poor survival of BMSCs. Mitophagy plays a vital role in maintaining cellular homeostasis and defending against oxidative stress because this process could control mitochondrial quality and quantity by eliminating dysfunctional or damaged mitochondria that can cause cell death. However, the accurate mechanisms of mitophagy in protecting BMSCs against the harshness of oxidative stress remain largely unknown. MAIN METHODS: BMSCs were treated with H2O2 for various time periods. Mitophagy response was evaluated through the expression levels of LC3-II, p62 and mitophagosomal formation by using Western blot and fluorescence analysis. Cell apoptosis was examined by flow cytometry and TUNEL assay. The interactions of mitophagy and apoptosis and the possible signalling pathways were investigated through the co-treatment of mitophagy inhibitor or mitophagy activator with H2O2. KEY FINDINGS: Oxidative stress rapidly facilitated mitophagy through JNK at an early stage but decreased mitophagy and increased apoptosis at a late stage. Furthermore, mitophagy inhibition significantly enhanced the apoptosis in the cells treated by H2O2. SIGNIFICANCE: Induced mitophagy may play pivotal roles in protecting cells against oxidative stress in BMSCs.

Molecular Regulation Mechanisms and Interactions Between Reactive Oxygen Species and Mitophagy.

The generation of reactive oxygen species (ROS) in response to oxidative stress has important effects on cell development, normal function, and survival. It may cause oxidative damage to intracellular macromolecular substances and mitochondria through several signaling pathways. However, the damaged mitochondria promote further ROS generation, creating a vicious cycle that can cause cellular injury. In addition, excessive ROS produced by damaged mitochondria can trigger mitophagy, a process that can scavenge impaired mitochondria and reduce ROS level to maintain stable mitochondrial function in cells. Therefore, mitophagy heaps maintain cellular homeostasis under oxidative stress. In this article, we review recent advances in cellular damage caused by excessive ROS, the mechanism of mitophagy, and the close relationship between ROS and mitophagy. This review provides a new perspective on therapeutic strategies for related diseases.

Comparison of percutaneous endoscopic lumbar discectomy versus microendoscopic discectomy for the treatment of lumbar disc herniation: a meta-analysis.

PURPOSE: We conducted a systematic review and meta-analysis to compare the clinical outcomes of percutaneous endoscopic lumbar discectomy (PELD) and microendoscopic discectomy (MED) for the treatment of lumbar disc herniation (LDH), and to clarify whether PELD is more superior to MED. METHODS: We performed a comprehensive search in the databases of MEDLINE, EMBASE, PubMed, Web of Science, Cochrane database, CNKI, and Wanfang Data to acquire all relevant studies up to July 2018. The searched literatures were then screened according to the strict inclusion and exclusion criteria. The critical data were extracted and analyzed utilizing Review Manager software. The pooled effects were calculated by mean difference (MD) or odds ratio (OR) with 95% confidence intervals (CI) on the basis of data attributes. RESULTS: A total of 18 studies (2161 patients, 1093 in the PELD group and 1068 in the MED group) were included in this systematic review and meta-analysis. At last follow-up, the results revealed that no significant difference was found between PELD group and MED group with respect to ODI (MD - 0.30; 95% CI - 1.02 to 0.42; P = 0.41), VAS-leg pain (MD - 0.18; 95% CI - 0.45 to 0.09; P = 0.19), VAS-unspecified (MD - 0.00; 95% CI - 0.05 to 0.04; P = 0.94), excellent & good rate (OR, 1.04; 95% CI 0.68 to 1.59; P = 0.86), total complication rate (OR, 0.96; 95% CI 0.65 to 1.43; P = 0.85), dural tear rate (OR, 0.39; 95% CI 0.10 to 1.55; P = 0.18), and residue or recurrence rate (OR, 2.22; 95% CI 1.02 to 4.83; P = 0.05). When compared to MED group, the PELD group showed significantly better results with regard to shorter length of incision (MD - 1.18; 95% CI - 1.39 to - 0.97; P < 0.00001), less blood loss (MD - 45.17; 95% CI - 64.74 to - 25.60; P < 0.00001), shorter post-operative in-bed time (MD - 59.11; 95% CI - 71.19 to - 47.04; P < 0.00001), shorter post-operative hospital stay (MD - 3.07; 95% CI - 4.81 to - 1.33; P < 0.00001), shorter total hospital stay (MD - 2.29; 95% CI - 3.03 to - 1.55; P < 0.00001), and lower VAS-back pain at last follow-up (MD - 0.77; 95% CI - 1.31 to - 0.24; P = 0.005), but with significantly worse results such as more fluoroscopy (MD 7.63; 95% CI 5.25 to 10.01; P < 0.00001) and higher re-operation rate (OR, 2.67; 95% CI 1.07 to 6.67; P = 0.04). Although no significant difference was found between the two groups in terms of duration of operation (MD 6.27; 95% CI - 2.44 to 14.98; P = 0.16) and total hospital cost (MD - 0.69; 95% CI - 12.60 to 11.23; P = 0.91), further subgroup analysis revealed that the duration of operation was significantly longer in the PELD group compared with the MED group in "Years before 2016" (MD 24.97; 95% CI 7.07 to 42.87; P = 0.006) and "Year 2016 to 2017" (MD 6.57; 95% CI 0.58 to 12.55; P = 0.03) subgroups but not in the subgroup "Year 2018" (MD - 5.66; 95% CI - 18.84 to 7.53; P = 0.40), and that the total hospital cost was significantly more in the PELD group compared with the MED group in the subgroup "Southeast of China" (MD 6.67; 95% CI 3.23 to 10.28; P = 0.0002) but not in the subgroup "Midwest of China" (MD - 8.09; 95% CI - 17.99 to 1.80; P = 0.11). CONCLUSIONS: For the treatment of LDH, both of PELD and MED can reach excellent results and no superiority was found between the two minimally invasive procedures with regard to duration of operation, ODI, VAS-leg pain, VAS-unspecified, excellent & good rate, total complication rate, dural tear rate, and residue or recurrence rate. While PELD can achieve better outcomes with respect to the length of incision, blood loss, post-operative in-bed time, post-operative hospital stay, total hospital stay, and VAS-back pain at last follow-up, however, MED showed certain advantages of less fluoroscopic times and lower re-operation rate. More practice and development are needed to make up for the deficiencies of PELD. Besides, the economic factor should also be considered according to different regions before making the treatment strategies. Well-defined randomized controlled trials with large samples are needed to further confirm these results.

Preclinical development of a microRNA-based therapy for intervertebral disc degeneration.

Understanding the molecular mechanisms regulating the maintenance and destruction of intervertebral disc may lead to the development of new therapies for intervertebral disc degeneration (IDD). Here we present evidence from miRNA microarray analyses of clinical data sets along with in vitro and in vivo experiments that miR-141 is a key regulator of IDD. Gain- and loss-of-function studies show that miR-141 drives IDD by inducing nucleus pulposus (NP) apoptosis. Furthermore, miR-141 KO in mice attenuated spontaneous and surgically induced IDD. Mechanistically, miR-141 promotes IDD development by targeting and depleting SIRT1, a negative regulator of NF-κB pathway. Therapeutically, upregulation or downregulation of miR-141 by nanoparticle delivery in IDD model aggravated or alleviated experimental IDD, respectively. Our findings reveal a novel mechanism by which miR-141, in part, promotes IDD progression by interacting with SIRT1/NF-κB pathway. Blockade of miR-141 in vivo may serve as a potential therapeutic approach in the treatment of IDD.

Lumbar disc herniation treated by microendoscopic discectomy : Prognostic predictors of long-term postoperative outcome.

PURPOSE: Microendoscopic discectomy (MED) is becoming an established and effective minimally invasive surgical method for the treatment of lumbar disc herniation (LDH); however, the absence of prognostic factors for long-term outcomes after MED results in a lack of specific criteria for appropriate patient selection. Therefore, we evaluated the long-term outcomes and associated predictors in patients who underwent MED for LDH. MATERIAL AND METHODS: Baseline and follow-up data for 664 LDH patients who suffered from sciatica and underwent primary MED were reviewed retrospectively. Variables at baseline that were analyzed as potential prognostic factors included sociodemographic characteristics, clinical findings, and imaging features. Follow-up data including improvements in the Visual Analog Scale (VAS) score and Oswestry Disability Index (ODI), postoperative low back pain (LBP), reoperation, and excellent/good results according to the modified MacNab criteria were set as outcome variables for univariate and further multivariate logistic regression analyses. RESULTS: The mean follow-up period was 63.8 ± 20.0 months (range 24-96 months). On average, sufficient improvements in both the VAS score (72.8%) and ODI (63.4%) were observed. In addition, a low postoperative LBP rate (23.9%), low reoperation rate (7.1%), and high rate of excellent/good clinical outcomes (89.9%) were achieved. A multivariate analysis indicated that older age, shorter disease duration, higher preoperative VAS score, lower preoperative ODI, shorter surgical time, lower severity of disc and adjacent disc degeneration, and lower severity of lumbar multifidus atrophy contributed to superior clinical outcomes. CONCLUSION: Excellent long-term outcomes after primary MED were achieved and specific sociodemographic, clinical, and imaging variables were identified as prognostic factors that can be used to guide patient selection and clinical decision making.

Resveratrol attenuated TNF-α-induced MMP-3 expression in human nucleus pulposus cells by activating autophagy via AMPK/SIRT1 signaling pathway.

Resveratrol (RSV) is known to play a role of anti-TNF-α in a number of cell types. However, whether RSV modulates the effects of TNF-α on human nucleus pulposus (NP) cells is unknown. The purpose of this study is to investigate whether RSV regulates TNF-α-induced matrix metalloproteinase-3 (MMP-3) expression. Via quantitative real-time polymerase chain reaction (qRT-PCR) analysis, we found that MMP-3 expression induced by TNF-α was inhibited by RSV treatment. Depending on Western blot and qRT-PCR assay, we found that RSV induced autophagy in human NP cells, whereas inhibition of autophagy remarkably abolished the restraining role of RSV in the TNF-α-mediated up-regulation of MMP-3. Furthermore, RSV increased SIRT1 expression and SIRT1 knockdown significantly suppressed RSV-induced autophagy in NP cells. RSV also activated AMP-activated protein kinase (AMPK), while inhibition of AMPK notably abolished RSV-induced SIRT1 expression. Our data showed that RSV attenuated TNF-α-induced MMP-3 expression in human NP cells by activating autophagy via AMPK/SIRT1 signaling pathway. This new finding suggested that RSV might act as a novel preventive and therapeutic role in intervertebral disc degeneration.

The presence of stem cells in potential stem cell niches of the intervertebral disc region: an in vitro study on rats.

PURPOSE: The potential of stem cell niches (SCNs) in the intervertebral disc (IVD) region, which may be of great significance in the regeneration process, was recently proposed. To the best of our knowledge, no previous in vitro study has examined the characteristics of stem cells derived from the potential SCN of IVD (ISN). Therefore, increasing knowledge on ISN-derived stem cells (ISN-SCs) may provide a greater understanding of IVD degeneration and regeneration processes. We aimed to demonstrate the existence of ISN-SCs and to compare their characteristics with bone marrow mesenchymal stem cells (BMSCs) in vitro. METHODS: Sprague-Dawley rats (male, 10-week-old) were used in this study. ISN tissues were separated by ophthalmic surgical instruments under a dissecting microscope according to the anatomical areas. BMSCs and cells isolated from the ISN tissues were cultured and expanded in vitro. Passage 4 populations were used for further analysis with respect to colony-forming ability, cellular immunophenotype, cell cycle, stem cell-related gene expression, and proliferation and multipotential differentiation capacities. RESULTS: In general, both of ISN-SCs and mesenchymal stromal cells (MSCs) met the minimal criteria for the definition of multipotent mesenchymal stromal cells, including adherence to plastic, specific surface antigen expression, and multipotent differentiation potential. Especially, ISN-SCs even showed greater potential of osteogenesis and chondrogenesis. The ISN-SCs also expressed stem cell-related genes that were comparable to those of BMSCs, and had colony-forming and self-renewal abilities. CONCLUSIONS: To the best of our knowledge, this is the first in vitro study aimed towards determining the existence and characteristics of ISN-SCs, which belong to the MSC family and with greater osteogenic and chondrogenic abilities than BMSCs according to our data. This finding may be of great significance for additional studies that investigate the migration of ISN-SCs into the IVD, and may provide a new perspective on different biological approaches for IVD self-regeneration.

Stem Cell Approaches to Intervertebral Disc Regeneration: Obstacles from the Disc Microenvironment.

Intervertebral disc (IVD) degeneration results in segmental instability and irritates neural compressive symptoms, such as low back pain and motor deficiency. The transplanting of stem cell into degenerative discs has attracted increasing clinical attention, as a new and proven approach to alleviating disc degeneration and to relieving discogenic pains. Aside from supplementation with stem cells, the IVD itself already contains a pool of stem and progenitor cells. Since the resident disc stem cells are incapable of reversing the pathologic changes that occur during aging and disc degeneration, it has been debated as to whether transplanted stem cells are capable of providing an efficient and durable therapeutic effect, even though there have been positive outcomes in both animal models and in clinical trials. This review aims to decipher the interactions between the stem cell and the disc microenvironment. Within their new niches in the IVD, the exogenous stem cell shows metabolic adaptation to the low-glucose supply, hypoxia, and compressive loadings, but demonstrates little tolerance to the disc-like acidity and hypertonicity. Similarly, the survival of endogenous stem cells is threatened as well by the harsh disc microenvironment, which may exhaust the stem cell resources and restrict the self-repair capacity of a degenerating IVD. To eliminate the intrinsic obstacles within the stressful disc niches, stem cells should be delivered with an injectable scaffold that provides both survival and mechanical support. Quick healing or concretion of the injection injuries, which minimizes stem cell leakage and disturbance to disc homeostasis, is of equal importance toward achieving efficient stem cell-based disc regeneration.

Tumor necrosis factor alpha promotes the proliferation of human nucleus pulposus cells via nuclear factor-κB, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase.

Although tumor necrosis factor alpha (TNF-α) is known to play a critical role in intervertebral disc (IVD) degeneration, the effect of TNF-α on nucleus pulposus (NP) cells has not yet been elucidated. The aim of this study was to explore the effect of TNF-α on proliferation of human NP cells. NP cells were treated with different concentrations of TNF-α. Cell proliferation was determined by cell counting kit-8 (CCK-8) analysis and Ki67 immunofluorescence staining, and expression of cyclin B1 was studied by quantitative real-time RT-PCR. Cell cycle was measured by flow cytometry and cell apoptosis was analyzed using an Annexin V-fluorescein isothiocyanate (FITC) & propidium iodide (PI) apoptosis detection kit. To identify the mechanism by which TNF-α induced proliferation of NP cells, selective inhibitors of major signaling pathways were used and Western blotting was carried out. Treatment with TNF-α increased cell viability (as determined by CCK-8 analysis) and expression of cyclin B1 and the number of Ki67-positive and S-phase NP cells, indicating enhancement of proliferation. Consistent with this, NP cell apoptosis was suppressed by TNF-α treatment. Moreover, inhibition of NF-κB, c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) blocked TNF-α-stimulated proliferation of NP cells. In conclusion, the current findings suggest that the effect of TNF-α on IVD degeneration involves promotion of the proliferation of human NP cells via the NF-κB, JNK, and p38 MAPK pathways.