Emodin ameliorates matrix degradation and apoptosis in nucleus pulposus cells and attenuates intervertebral disc degeneration through LRP1 in vitro and in vivo.

Low back pain (LBP) is the leading cause of disability worldwide, with a strong correlation to intervertebral disc degeneration (IDD). Inflammation-induced extracellular matrix (ECM) degradation plays a major role in IDD's progression. Emodin, known for its anti-inflammatory effects and ability to inhibit ECM degradation in osteoarthritis, but its role in IDD is unclear. Our study aimed to explore emodin's role and mechanisms on IDD both in vivo and in vitro. We discovered that emodin positively regulated anabolic markers (COL2A1, aggrecan) and negatively impacted catabolic markers (MMP3, MMP13) in nucleus pulposus cells, while also inhibiting cell apoptosis under inflammation environment. We revealed that emodin inhibits inflammation-induced NF-ĸB activation by suppressing the degradation of LRP1 via the proteasome pathway. Additionally, LRP1 was validated as essential to emodin's regulation of ECM metabolism and apoptosis, both in vitro and in vivo. Ultimately, we demonstrated that emodin effectively alleviates IDD in a rat model. Our findings uncover the novel pathway of emodin inhibiting ECM degradation and apoptosis through the inhibition of NF-κB via LRP1, thus alleviating IDD. This study not only broadens our understanding of emodin's role and mechanism in IDD treatment but also guides future therapeutic interventions.

Correlation between posterior paraspinal muscle atrophy and lumbar intervertebral disc degeneration in patients with chronic low back pain.

BACKGROUND: Although enormous studies have been devoted to solving the problem of intervertebral disc degeneration/herniation, little attention is paid to the effect of paraspinal muscles on it. We aimed to investigate the correlation between paraspinal muscle atrophy and lumbar disc degeneration to recognize paraspinal muscle atrophy and its importance to the spine. PATIENTS AND METHODS: A total of 107 patients were enrolled in the study (65 females, 42 males; age 50.87 ± 15.391 years old). Cross-sectional area, functional cross-sectional area, and fatty infiltration of the posterior paraspinal muscles were measured at the level of L4/5, and the degree of facet joint degeneration was evaluated at the levels of L3/4, L4/5, and L5/S1 by MRI. After controlling the confounding factors by multiple linear regression, the correlations among paraspinal muscle atrophy, disc degeneration, and facet joint degeneration were analyzed. Meanwhile, Pearson/Spearson rank analysis was used to analyze the correlation between clinical symptoms (VAS and ODI) and paraspinal muscle atrophy. RESULTS: There was a strong correlation between paraspinal muscle atrophy and disc degeneration after controlling the confounding factors (p < 0.05, R > 0.5). There was a weak correlation between paraspinal muscle atrophy and facet joint degeneration (p < 0.05, R < 0.5). There was a significant correlation between facet joint degeneration and intervertebral disc degeneration (p < 0.05, R > 0.7). The fatty infiltration of paraspinal muscle was weakly correlated with ODI (p < 0.05, R < 0.3), but VAS was not. CONCLUSIONS: The degree of paraspinal muscle atrophy increased with lumbar disc degeneration and facet joint degeneration and fatty infiltration of multifidus was more susceptible to weight.

Comprehensive analysis of angiogenesis pattern and related immune landscape for individual treatment in osteosarcoma.

Postoperative recurrence and metastasis are the main reasons for the poor prognosis of osteosarcoma (OS). Currently, an ideal predictor for not only prognosis but also drug sensitivity and immunotherapy responses in OS patients is urgently needed. Angiogenesis plays a crucial role in tumour progression, which suggests its immense potential for predicting prognosis and responses to immunotherapy for OS. Angiogenesis patterns in OS were explored in depth in this study to construct a prognostic model called ANGscore and clarify the underlying mechanism involved in the immune microenvironment. The efficacy and robustness of the model were validated in multiple datasets, including bulk RNA-seq datasets (TARGET-OS, GSE21257), a single-cell RNA-seq dataset (GSE152048) and immunotherapy-related datasets (GSE91061, GSE173839). OS patients with a high ANGscore had a worse prognosis, accompanied by the immune desert phenotype. Pseudotime and cellular communication analyses in scRNA-seq data revealed that as the ANGscore increased, the malignant degree of cells increased, and IFN-γ signalling was involved in tumour progression and regulation of the tumour immune microenvironment. Furthermore, the ANGscore was associated with immune cell infiltration and the response rate to immunotherapy. OS patients with high ANGscore might be resistant to uprosertib, and be sensitive to VE821, AZD6738 and BMS.345541. In conclusion, we established a novel ANGscore system by comprehensively analysing the expression pattern of angiogenesis genes, which can accurately differentiate the prognosis and immune characteristics of OS populations. Additionally, the ANGscore can be used for patient stratification during immunotherapy, and guide individualized treatment strategies.

Biomechanical effects of cement discoplasty on the lumbar spinal unit.

Background: Percutaneous cement discoplasty (PCD) is used to treat patients with low back and leg pain due to the intervertebral disc vacuum phenomena. Whether PCD can restore lumbar spinal stability remains unknown. Objective: The purpose of our in vitro study was to evaluate the biomechanical changes brought about by PCD. Methods: Eight fresh pig lumbar spines were tested in the following order: intact, after nucleotomy, and after discoplasty. Flexion/extension, lateral bending, and axial rotation were induced by pure moments. The range of motion and neutral zone were recorded. A CT scan was performed to assess the injection volume of the bone cement and to observe whether the bone cement was fractured. After removing the facet joint, a compression failure test was conducted to observe the fracture of bone cement. Results: Compared with nucleotomy, range of motion (ROM) after discoplasty was reduced only in lateral flexion (P < 0.05). The results of the neutral zone showed that the neutral zones in flexion-extension and lateral bending were significantly reduced after discoplasty (P < 0.05). The neutral zone was more sensitive to changes in lumbar stability than ROM. Bone cement slides were observed during the biomechanical test. The CT scan and compression failure test showed that bone cement fracture was more likely to occur at the puncture channel in the annulus fibrosus region. Conclusion: In all, the biomechanical study indicates that discoplasty helps enhance the stability of the lumbar spine in flexion-extension and lateral bending, which explains how PCD works for low back pain. Fractures and sliding of bone cement were observed after discoplasty, and this was more likely to occur at the puncture channel in the annulus fibrosus region. This suggests that bone cement displacement after PCD may cause nerve compression.

AOSRV: Development and preliminary performance assessment of a new robotic system for autonomous percutaneous vertebroplasty.

BACKGROUND: Percutaneous vertebroplasty (PVP) is one of the most effective treatments for patients with vertebral fracture that need surgical treatment, and surgical robotics are promising tools to provide surgeons with improved precision, surgical efficiency and reduce radiation exposure. However, there are currently few robotics that are developed to help assist with PVP. METHODS: A new spinal surgical robotic system 'AOSRV' for autonomous vertebral puncture and bone cement injection was designed and customised in this study. To investigate its practical abilities and the advantages, we performed single-segment/double-segment PVP simulation surgeries on pig spinal specimens manually and using AOSRV. RESULTS: By contrast with the freehand group (FG) in single-segment (SS)/double-segment (DS) surgery, the robotic group (RG) was superior in the operation time (RGSS = 21.14 ± 4.11 min, FGSS = 33.17 ± 6.83 min; RGDS = 42.39 ± 7.31 min, FGDS = 62.86 ± 20.39 min), puncture adjustments (RGSS = 2.30 ± 1.77, FGSS = 14.86 ± 5.46; RGDS = 3.91 ± 1.76, FGDS = 20.00 ± 7.76), intraoperative fluoroscopies (RGSS = 4.10 ± 1.52, FGSS = 20.57 ± 5.44; RGDS = 7.82 ± 1.40, FGDS = 25.91 ± 7.23) and bone cement leakage rate (RGSS = 30%, FGSS = 71.4%; RGDS = 38.6%, FGDS = 83.3%). CONCLUSIONS: AOSRV was successfully developed and had a promising preliminary performance. An innovative attempt was made for the blank space of the autonomous vertebroplasty surgical robotics, and it may shed a light on more promising applications in the future.

Androgen Maintains Intestinal Homeostasis by Inhibiting BMP Signaling via Intestinal Stromal Cells.

Research shows a higher incidence of colorectal cancer in men. However, the molecular mechanisms for this gender disparity remain unknown. We report the roles of androgen in proliferation and differentiation of intestinal stem cells via targeting of the androgen receptor (AR) on intestinal stromal cells by negatively regulating BMP signaling. Orchidectomy (ORX) or the AR antagonist promotes expansion of intestinal epithelium but suppresses intestinal stem cell (ISC) proliferation. Conversely, the AR agonist inhibits ISC differentiation but augments proliferation in ovariectomized mice. Mechanistically, activation of the AR increases expression of BMP antagonists but lowers expression of BMP4 and Wnt antagonists in primary stromal cells, which promotes intestinal organoid growth. Interestingly, the BMP pathway inhibitor LDN-193189 reverses the ORX-induced effects. Our results highlight that stromal cells constitute the intestinal stem cell niche and provide a possible explanation for higher incidence rates of colorectal cancer in men.

[The relationship between abnormal apoptosis and Fas expression of thymocytes from patients with myasthenia gravis].

AIM: To explore the roles of abnormalities of thymocytic abnormal apoptosis and its Fas expression in patients with myasthenia gravis (MG) in generation of autoimmune response. METHODS: The thymocytes were isolated and thymus extractive was prepared from fresh thymic tissue excised from MG patients. The proliferation of thymocyes was evaluated by MTT colorimetry. The apoptosis of thymocytes were examined by DNA electrophoresis. Expression of Fas was analyzed by a FACScan flow cytometry. Transcription and mutation of Fas gene were detected by RT-PCR and single-stranded conformation polymorphism ( SSCP) analysis. RESULTS: Thymus extractive could inhibit proliferation of normal thymocytes, while had no influence on the thymocytic proliferation of MG patients. The proliferation of thymocytes of both normal persons and MG patients could be inhibited by thymus extractive in the presence of dexamethasone. The inhibition rates were 58. 33% and 54. 26% respectively. The cocultured thymocytes with dexamethasone showed characteristic apoptosis pattern and the DNA electrophoresis exhibited 'ladder' appearance. The abnormal bands in Fas mRNA of partial MG patients' thymocytes were found by RT-PCR-SSCP analysis. CONCLUSION: Abnormalities of apoptosis and Fas gene expression of MG patients' thymocytes, and Fas gene mutation may be related to the pathogenesis and progression of MG.