Osteoporosis is a serious public health problem that results in fragility fractures, especially in postmenopausal women. Because the current therapeutic strategy for osteoporosis has various side effects, a safer and more effective treatment is worth exploring. It is important to examine natural plant extracts during new drug design due to low toxicity. Mogrol is an aglycon of mogroside, which is the active component of Siraitia grosvenorii (Swingle) and exhibits anti-inflammatory, anticancer and neuroprotective effects. Here, we demonstrated that mogrol dose-dependently inhibited osteoclast formation and function. To confirm the mechanism, RNA sequencing (RNA-seq), real-time PCR (RT–PCR), immunofluorescence and Western blotting were performed. The RNA-seq data revealed that mogrol had an effect on genes involved in osteoclastogenesis. Furthermore, RT–PCR indicated that mogrol suppressed osteoclastogenesis-related gene expression, including CTSK, ACP5, MMP9 and DC-STAMP, in RANKL-induced bone marrow macrophages Western blotting demonstrated that mogrol suppressed osteoclast formation by blocking TNF receptor-associated factor 6 (TRAF6)-dependent activation of the mitogen-activated protein kinase nuclear factor-B (NF-κB) signaling pathway, which decreased two vital downstream transcription factors, the nuclear factor of activated T cells calcineurin-dependent 1 (NFATc1) and c-Fos proteins expression. Furthermore, mogrol dramatically reduced bone mass loss in postmenopausal mice. In conclusion, these data showed that mogrol may be a promising procedure for osteoporosis prevention or therapy.
Purpose To investigate induction of cell death in Osteosarcoma (OS) using the anti-tuberculosis drug, rifampicin, loaded into exosomes. Patients and Methods BMSC-exosomes were isolated by ultracentrifugation and loaded ultrasonically with rifampicin. Nanoparticle exosome-rifampicin (EXO-RIF) was added to the OS cell-lines, 143B and MG63, in vitro, to observe the growth inhibitory effect. In vivo experiments were conducted by injecting fluorescently labeled EXO-RIF through the tail vein of 143B cell xenograft nude mice and tracking distribution. Therapeutic and toxic side-effects were analyzed systemically. Results Sonication resulted in encapsulation of rifampicin into exosomes. Exosome treatment accelerated the entry of rifampicin into OS cells and enhanced the actions of rifampicin in inhibiting OS proliferation, migration and invasion. Cell cycle arrest at the G2/M phase was observed. Dynamin-related protein 1 (Drp1) was activated by EXO-RIF and caused mitochondrial lysis and apoptosis. Exosome treatment targeted rifampicin to the site of OS, causing OS apoptosis and improving mouse survival in vivo. Conclusion The potent Drp1 agonist, rifampicin, induced OS apoptosis and exosome loading, improving OS targeting and mouse survival rates. EXO-RIF is a promising strategy for the treatment of diverse malignancies.
Rationale: We report a case of Schmorl node induced multiple radiculopathy. Patient concerns: A 70-year-old female patient complained of lower back pain in the left leg accompanied by numbness and weakness. Diagnosis: Radiographs showed obvious osteoporosis in the lumbar vertebrae. Computed tomography demonstrated a hole in the upper posterior half of the L2 vertebral body. Magnetic resonance imaging of the lumbar spine revealed a herniated disc involving a protrusion at the posterior wall of the L2 vertebral body, which was present in the left lateral and dorsal epidural spaces. There was significant lumbar stenosis at the L2 vertebral body secondary to dural sac compression due to the mass. Intervention: Left-sided hemilaminectomy was performed at L2 with screw fixation at L1–3. Intraoperatively, the severely ruptured disc compression in the dural sac and nerve root was removed. Outcomes: The patient's leg pain was immediately resolved, and her back pain was reduced. The patient recovered normal motor function at 20 days after surgery. Lessons: A Schmorl node can progress and break through the lumbar vertebral body, resulting in nerve compression. A large proximal herniated mass can cause distal multiple radiculopathy. Therefore, this special case of Schmorl node with multiple radiculopathy should be treated by removing the proximal herniated nucleus pulposus from the vertebral body.
Introduction: Intradural schwannomas can occur at any level of the spine. According to the literature, approximately 8% of intradural schwannomas occur in the atlantoaxial spine, and these tumors are usually located in the posterolateral or lateral spinal cord. In contrast, tumors in the ventral midline of the spinal cord are relatively rare. Patient concerns: A 47-year-old female presented with progressively worsening neck pain and paresthesias in both upper and lower limbs for the past 5 years. Diagnosis: Based on Magnetic Resonance Imaging and histopathological findings, she was diagnosed with ventral midline primary schwannoma of the cervical spinal cord. Interventions: The patient was treated with surgical resection. Outcomes: Follow-up visit at 2 years after the surgery showed that the patient is neurologically intact and free of disease. Conlusion: In summary, for the tumors in the ventral midline of the atlantoaxial spinal cord, the preferred treatment is complete surgical resection by the posterior approach compared to the anterior approach, which often improves clinical symptoms or achieves a healing effect.
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