Search

Baixing Li,* Xiao Yang,* Pu Zhang, Jiadong Guo, Kewei Rong, Xin Wang, Xiankun Cao, Tangjun Zhou, Jie Zhao Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics, Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tangjun Zhou; Jie Zhao, Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics, Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, People’s Republic of China, Tel +8621-23271159, Fax +8621-63139920, Email zhoutangjun@outlook.com; profzhaojie@126.comPurpose: Low back pain (LBP) induced by intervertebral disc degeneration (IDD) brings progressively painful status and impairs the normal daily living. Engeletin is a plant-derived medicine with anti-inflammation and antioxidant functions. Therefore, we aim to confirm its protective effects against the intervertebral disc degeneration in vivo and in vitro.Methods: The cytotoxicity of engeletin was validated by CCK-8 tests. Using the TNF-α to simulate the inflammation status in vitro, the expression of inflammatory mediators and MMP families were determined by qPCR, Western blotting and confocal microscopy. Cell apoptosis was analyzed by flow cytometry and TUNEL assay. The expression of apoptosis-related proteins was tested by Western blotting. The activation of NF-κB and MAPK pathways was evaluated by Western blotting and confocal microscopy. In vivo, percutaneous needle puncture was used to establish the IDD model in rat, and engeletin was administrated via intradiscal injection. The therapeutic effects of engeletin were detected through imaging and histology analysis.Results: Cell viability tests demonstrated there was little cytotoxicity of engeletin toward NP cells. Pretreatment with engeletin effectively ameliorate the TNF-α-induced up-regulation of inflammatory mediators and MMP families, promoting the anabolism of ECM meanwhile. Cell apoptosis was also attenuated with the addition of engeletin. We found that the activation of MAPK and NF-κB signaling pathways and the nuclear translocation of phosphorylated p65 and p38 were inhibited prominently with the treatment of engeletin which may be the potential molecular mechanism for its anti-inflammation effects. Finally, the IDD induced by percutaneous needle puncture was partially alleviated with the injection of engeletin in vivo.Conclusion: As a natural compound with little cytotoxicity, engeletin possesses the outstanding anti-inflammation and anti-apoptosis effects in the process of IDD in vitro and in vivo, which may be a promising medicine for the prevention and treatment of IDD-related low back pain.Keywards: intervertebral disc degeneration, engeletin, nucleus pulposus, inflammation, apoptosis, NF-κB and MAPK signaling pathways

Apoptosis and extracellular matrix degradation of the nucleus pulposus are the main initiators of intervertebral disc degeneration (IVDD) and can be explained by endoplasmic reticulum (ER) stress. Thus, pharmacological therapy aimed at suppressing this pathway may be a promising approach for the management of intervertebral disc degeneration. In this study, we aimed to explore the protective effects of Sal003 against intervertebral disc degeneration and its underlying mechanisms. Thapsigargin (Tg)-stimulated rat nucleus pulposus cells and a needle puncture-induced intervertebral disc degeneration rat model were used to explore the protective effects of Sal003. Our results showed that Sal003 inhibited apoptosis and extracellular matrix degradation by suppressing the endoplasmic reticulum stress pathway. The therapeutic effects of Sal003 were also observed in the intervertebral disc degeneration rat model, as evidenced by improved degeneration along with decreased apoptosis and extracellular matrix degradation in intervertebral discs. Our results demonstrated Sal003 as a potential treatment for intervertebral disc degeneration.

Low back pain (LBP) caused by intervertebral disc degeneration (IVDD) is accredited to the release of inflammatory cytokines followed by biomechanical and structural deterioration. In our study, we used a plant-derived medicine, curcumenol, to treat IVDD. A cell viability test was carried out to evaluate the possibility of using curcumenol. RNA-seq was used to determine relative pathways involved with curcumenol addition. Using TNFα as a trigger of inflammation, the activation of the NF-κB signaling pathway and expression of the MMP family were determined by qPCR and western blotting. Nucleus pulposus (NP) cells and the rats’ primary NP cells were cultured. The catabolism status was evaluated by an ex vivo model. A lumbar instability mouse model was carried out to show the effects of curcumenol in vivo. In general, RNA-seq revealed that multiple signaling pathways changed with curcumenol addition, especially the TNFα/NF-κB pathway. So, the NP cells and primary NP cells were induced to suffer inflammation with the activated TNFα/NF-κB signaling pathway and increased expression of the MMP family, such as MMP3, MMP9, and MMP13, which would be mitigated by curcumenol. Owing to the protective effects of curcumenol, the height loss and osteophyte formation of the disc could be prevented in the lumbar instability mouse model in vivo.

Low back pain (LBP) caused by intervertebral disc degeneration (IVDD) is accredited to the release of inflammatory cytokines followed by biomechanical and structural deterioration. In our study, we used a plant-derived medicine, curcumenol, to treat IVDD. A cell viability test was carried out to evaluate the possibility of using curcumenol. RNA-seq was used to determine relative pathways involved with curcumenol addition. Using TNFα as a trigger of inflammation, the activation of the NF-κB signaling pathway and expression of the MMP family were determined by qPCR and western blotting. Nucleus pulposus (NP) cells and the rats' primary NP cells were cultured. The catabolism status was evaluated by an

The financial crisis results in a sluggish market, which makes enterprises more cautious with investment. In this paper, we first try to examine the maturity of the Chinese market; then elaborate on the different types of futures related to the enterprises’ products and select the quality futures; and then, use the covariance model to obtain the related coefficient and make a hedge analysis of investment portfolio, thus trying to maximize the gains under equal risks, or minimize the risks under equal gains, and reduce the risks by adjusting the investment portfolio structure of the invested commodity futures; and lastly, we make a comparison of the variance between investment portfolio optimized by relevant futures and investment portfolio that have not yet joined in futures, evaluate the reduction of risks and make adjustments of the investment portfolio, thus enabling the enterprises to achieve the goals of using futures portfolio to optimize the investment structure and to evade the financial risks. Research results show: (1) Affected by the financial crisis and the theory of consumers’ utility maximization, the present-day production enterprises are risk-tired investors; (2) the futures market in China cannot be called a mature market, so the short-term futures investment of individual products has a very high risk, and many are noise traders, so production enterprises should consider building the futures portfolio and make a long-term investment; (3) when selecting a futures portfolio, it can be either the positively relevant futures or the negatively relevant futures, and both can help reduce the financial risks; and (4) enterprises can make more profits if they adjust investment portfolio correctly.