As the principal reason for low back pain, intervertebral disc degeneration (IDD) affects the health of people around the world regardless of race or region. Degenerative discs display a series of characteristic pathological changes, including cell apoptosis, senescence, remodeling of extracellular matrix, oxidative stress and inflammatory local microenvironment. As a serine/threonine-protein kinase in eukaryocytes, AMP-activated protein kinase (AMPK) is involved in various cellular processes through the modulation of cell metabolism and energy balance. Recent studies have shown the abnormal activity of AMPK in degenerative disc cells. Besides, AMPK regulates multiple crucial biological behaviors in IDD. In this review, we summarize the pathophysiologic changes of IDD and activation process of AMPK. We also attempt to generalize the role of AMPK in the pathogenesis of IDD. Moreover, therapies targeting AMPK in alleviating IDD are analyzed, for better insight into the potential of AMPK as a therapeutic target.
Methylprednisolone (MP) is the drug of choice for treating spinal cord injury (SCI), but the aggressive dosage regimen used often results in adverse side effects. Therefore, MP should be combined with other drugs to lower the required dose. Melatonin is effective in alleviating nerve damage and inhibiting axonal degeneration. The combination of melatonin and half-dose methylprednisolone (HMP) for spinal cord injury treatment has never been reported. In this study, we established a rat model of T9 spinal cord injury by the Allen’s method and assessed the synergistic therapeutic effects of melatonin and HMP by factorial design. Our results demonstrated that melatonin could synergize with HMP to ameliorate acute SCI through PI3K-AKT1 pathway. Combining melatonin with HMP significantly reduced the standard-dose of methylprednisolone and limited its adverse reactions, representing a promising option for treating acute SCI.
Patients with spinal muscular atrophy (SMA) are susceptible to the respiratory infections and might be at a heightened risk of poor clinical outcomes upon contracting coronavirus disease 2019 (COVID-19). In the face of the COVID-19 pandemic, the potential associations of SMA with the susceptibility to and prognostication of COVID-19 need to be clarified. We documented an SMA case who contracted COVID-19 but only developed mild-to-moderate clinical and radiological manifestations of pneumonia, which were relieved by a combined antiviral and supportive treatment. We then reviewed a cohort of patients with SMA who had been living in the Hubei province since November 2019, among which the only 1 out of 56 was diagnosed with COVID-19 (1.79%, 1/56). Bioinformatic analysis was carried out to delineate the potential genetic crosstalk between SMN1 (mutation of which leads to SMA) and COVID-19/lung injury-associated pathways. Protein-protein interaction analysis by STRING suggested that loss-of-function of SMN1 might modulate COVID-19 pathogenesis through CFTR, CXCL8, TNF and ACE. Expression quantitative trait loci analysis also revealed a link between SMN1 and ACE2, despite low-confidence protein-protein interactions as suggested by STRING. This bioinformatic analysis could give hint on why SMA might not necessarily lead to poor outcomes in patients with COVID-19.
Background: Both patients with Chiari-I malformation (CIM) with syringomyelia and those with idiopathic syringomyelia (ISm) have a syrinx and can have scoliosis as well. However, there is no literature regarding differences between CIM and ISm in terms of radiographic outcomes and surgical complications after posterior fusion, to our knowledge. The aim of the present study was to compare radiographic features, clinical outcomes, and surgical complications after posterior spinal fusion between patients with CIM-associated scoliosis and those with ISm-associated scoliosis. Methods: One hundred and twenty patients with syringomyelia-associated scoliosis were retrospectively analyzed. Twenty-one patients with scoliosis secondary to CIM were enrolled and matched by sex, age, and the Cobb angle of the scoliotic curve with 21 patients with scoliosis secondary to ISm. All patients underwent 1-stage posterior fusion surgery. Coronal and sagittal radiographic parameters were evaluated before surgery, immediately after surgery, and at the final follow-up (at least 2 years). We also collected data regarding syringeal features, neurological deficits, intraoperative neuromonitoring, and complications. Results: Sex, age, preoperative coronal/sagittal scoliosis parameters, and neurological deficits were similar between the matched CIM and ISm groups. On average, the CIM group had a longer syrinx (12.3 ± 3.6 versus 8.9 ± 4.5 vertebral levels, p = 0.010) than the ISm group. The CIM and ISm groups showed similar correction rates for primary curves (70.9% ± 10.6% versus 69.5% ± 16.3%, p = 0.739). There were no significant differences in coronal/sagittal correction, intraoperative neuromonitoring abnormalities, surgical complications, or Scoliosis Research Society-22 questionnaire scores between the 2 groups. Conclusions: Despite matched demographic and scoliotic coronal parameters, patients with CIM had longer syrinxes compared with patients with ISm. One-stage posterior fusion achieved comparable clinical and radiographic outcomes for both CIM- and ISm-associated scoliosis without significant differences in neurological complications. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
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