Association of spinopelvic index with proximal junctional failure developing in adult spinal deformity after surgical treatment: an observational study.

BACKGROUND: Those pelvic parameters of sacral slope (SS) and pelvic tilt (PT) correlated significantly to lumbar spine and hip joints respectively. We proposed the match between SS and PT, namely spinopelvic index (SPI), in order to investigate whether the SPI correlated to proximal junctional failure (PJF) in adult spinal deformity (ASD) after correction surgery. METHODS: Ninety-nine ASD patients who had undergone long-fusion (≥ 5 vertebras) surgeries were reviewed retrospectively in two medical institutions from January 2018 to December 2019. Those SPI were calculated with the equation: SPI = SS/PT, and analyzed using the receiver operating characteristic curve (ROC) analysis. All participants were subdivided into the observational and control group. Comparisons of demographics, surgical and radiographic data between the two groups were performed. A Kaplan-Meier curve and log-rank test was used to analyze the differences in PJF-free survival time, and the 95% confidence intervals (CI) were recorded respectively. RESULTS: Nineteen patients suffering from PJF had much smaller postoperative SPI (P = 0.015), but much larger TK postoperatively (P < 0.001). ROC analysis determined the best cutoff value of 0.82 for SPI (sensitivity = 88.5%, specificity = 57.9%; AUC = 0.719, 95%CI: 0.612-0.864; P = 0.003). There were 19 and 80 cases in the observational (SPI ≤ 0.82) and control group (SPI > 0.82) respectively. The incidence of PJF in the observational group was much higher (11/19 VS 8/80, P < 0.001); further logistic regression analysis showed that SPI ≤ 0.82 was associated with increased odds of PJF (odds ratio: 12.375; 95%CI: 3.851-39.771). PJF-free survival time in the observational group decreased significantly (P < 0.001, log-rank test), moreover, multivariate analysis demonstrated that a value of SPI ≤ 0.82 (HR 6.626, 95%CI: 1.981-12.165) was significantly associated with PJF. CONCLUSIONS: For ASD patients underwent long-fusion surgeries, the SPI should be over 0.82. The incidence of PJF may increase by 12-fold in such individuals with the immediate SPI ≤ 0.82 postoperatively.

Cell death regulation: A new way for natural products to treat osteoporosis.

Osteoporosis is a common metabolic bone disease that results from the imbalance of homeostasis within the bone. Intra-bone homeostasis is dependent on a precise dynamic balance between bone resorption by osteoclasts and bone formation by mesenchymal lineage osteoblasts, which comprises a series of complex and highly standardized steps. Programmed cell death (PCD) (e.g., apoptosis, autophagy, ferroptosis, pyroptosis, and necroptosis) is a cell death process that involves a cascade of gene expression events with tight structures. These events play a certain role in regulating bone metabolism by determining the fate of bone cells. Moreover, existing research has suggested that natural products derived from a wide variety of dietary components and medicinal plants modulate the PCDs based on different mechanisms, which show great potential for the prevention and treatment of osteoporosis, thus revealing the emergence of more acceptable complementary and alternative drugs with lower costs, fewer side effects and more long-term application. Accordingly, this review summarizes the common types of PCDs in the field of osteoporosis. Moreover, from the perspective of targeting PCDs, this review also discussed the roles of currently reported natural products in the treatment of osteoporosis and the involved mechanisms. Based on this, this review provides more insights into new molecular mechanisms of osteoporosis and provides a reference for developing more natural anti-osteoporosis drugs in the future.

Bushen Huoxue Formula Modulates Autophagic Flux and Inhibits Apoptosis to Protect Nucleus Pulposus Cells by Restoring the AMPK/SIRT1 Pathway.

Background: Low back pain (LBP) has the characteristics of chronic and persistence, which is a heavy social burden. Intervertebral disc degeneration (IVDD) is a major cause of LBP. The typical features of IVDD are extracellular matrix (ECM) degradation and nucleus pulposus cell (NP) apoptosis. Bushen Huoxue Formula (BSHXF) has good clinical effects on LBP. However, the mechanism of BSHXF affecting ECM and NP cells is still unclear. Aim of the Study. In this study, the impact of BSHXF on autophagy and apoptosis of NP cells was studied through the AMPK/SIRT1 pathway. Material and Methods. NP cells were extracted through the digestion of collagenase and trypsin, and the components of BSHXF were identified. Cell Counting Kit-8 was applied to detect the impact of BSHXF on NP cells. Mitochondrial function was detected using MitoTracker assay, ATP kit, and SOD kit. Autophagy and apoptosis were detected by RT-qPCR, western blotting, and flow cytometry. Results: BSHXF promoted NP cell survival in a concentration-dependent manner, and the elimination of rat serum did not increase cell proliferation; TNF-α accelerated ECM degradation, ROS accumulation, and NP cell apoptosis and decreased autophagic flux. BSHXF restored mitochondrial function and autophagic flux. In addition, AMPK/SIRT1 pathway activation was associated with IVDD. Conclusions: BSHXF regulates autophagy and enhances autophagic flux to suppress excessive ROS production and restore mitochondrial function in an AMPK/SIRT1-dependent manner. However, the protection of BSHXF on TNF-α-treated cells was eliminated by 3-MA. Furthermore, the protective impact of BSHXF on ECM degradation and apoptosis induced by TNF-α was restrained by an AMPK inhibitor. Therefore, maintaining the proper autophagy illustrates treatment strategy for IVDD.

Naringin protects human nucleus pulposus cells against TNF-α-induced inflammation, oxidative stress, and loss of cellular homeostasis by enhancing autophagic flux via AMPK/SIRT1 activation.

Activation of the proinflammatory-associated cytokine, tumor necrosis factor-α (TNF-α), in nucleus pulposus (NP) cells is essential for the pathogenesis of intervertebral disc degeneration (IDD). Restoring autophagic flux has been shown to effectively protect against IDD and is a potential target for treatment. The goal of this study was to explore particular autophagic signalings responsible for the protective effects of naringin, a known autophagy activator, on human NP cells. The results showed that significantly increased autophagic flux was observed in NP cells treated with naringin, with pronounced decreases in the inflammatory response and oxidative stress, which rescued the disturbed cellular homeostasis induced by TNF-α activation. Autophagic flux inhibition was detectable in NP cells cotreated with 3-methyladenine (3-MA, an autophagy inhibitor), partially offsetting naringin-induced beneficial effects. Naringin promoted the expressions of autophagy-associated markers via SIRT1 (silent information regulator-1) activation by AMPK (AMP-activated protein kinase) phosphorylation. Either AMPK inhibition by BML-275 or SIRT1 silencing partially counteracted naringin-induced autophagic flux enhancement. These findings indicate that naringin boosts autophagic flux through SIRT1 upregulation via AMPK activation, thus protecting NP cells against inflammatory response, oxidative stress, and impaired cellular homeostasis. Naringin can be a promising inducer of restoration autophagic flux restoration for IDD.