Aims. This study was performed to explore the effect of melatonin on pyroptosis in nucleus pulposus cells (NPCs) and the underlying mechanism of that effect. Methods. This experiment included three patients diagnosed with lumbar disc herniation who failed conservative treatment. Nucleus pulposus tissue was isolated from these patients when they underwent surgical intervention, and primary NPCs were isolated and cultured. Western blotting, reverse transcription polymerase chain reaction, fluorescence staining, and other methods were used to detect changes in related signalling pathways and the ability of cells to resist pyroptosis. Results. Western blot analysis confirmed the expression of cleaved CASP-1 and melatonin receptor (MT-1A-R) in NPCs. The cultured NPCs were identified by detecting the expression of CD24, collagen type II, and aggrecan. After treatment with hydrogen peroxide, the pyroptosis-related proteins NLR family pyrin domain containing 3 (NLRP3), cleaved CASP-1, N-terminal fragment of gasdermin D (GSDMD-N), interleukin (IL)-18, and IL-1β in NPCs were upregulated, and the number of propidium iodide (PI)-positive cells was also increased, which was able to be alleviated by pretreatment with melatonin. The protective effect of melatonin on pyroptosis was blunted by both the melatonin receptor antagonist luzindole and the nuclear factor erythroid 2–related factor 2 (Nrf2) inhibitor ML385. In addition, the expression of the transcription factor Nrf2 was up- or downregulated when the melatonin receptor was activated or
In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD. An in vitro model for oxidative stress-induced injury in NPCs was developed to elucidate the mechanisms underlying the upregulation of DDIT4 expression, activation of the reactive oxygen species (ROS)-thioredoxin-interacting protein (TXNIP)-NLRP3 signalling pathway, and nucleus pulposus pyroptosis. Furthermore, the mechanism of action of small interfering DDIT4 (siDDIT4) on NPCs in vitro was validated. A triplex hydrogel named siDDIT4@G5-P-HA was created by adsorbing siDDIT4 onto fifth-generation polyamidoamine (PAMAM) dendrimer using van der Waals interactions, and then coating it with hyaluronic acid (HA). In addition, we established a rat puncture IVDD model to decipher the hydrogel’s mechanism in IVDD.Aims
Methods
People with severe, persistent low back pain (LBP) may be offered lumbar spine fusion surgery if they have had insufficient benefit from recommended non-surgical treatments. However, National Institute for Health and Care Excellence (NICE) 2016 guidelines recommended not offering spinal fusion surgery for adults with LBP, except as part of a randomized clinical trial. This survey aims to describe UK clinicians’ views about the suitability of patients for such a future trial, along with their views regarding equipoise for randomizing patients in a future clinical trial comparing lumbar spine fusion surgery to best conservative care (BCC; the FORENSIC-UK trial). An online cross-sectional survey was piloted by the multidisciplinary research team, then shared with clinical professional groups in the UK who are involved in the management of adults with severe, persistent LBP. The survey had seven sections that covered the demographic details of the clinician, five hypothetical case vignettes of patients with varying presentations, a series of questions regarding the preferred management, and whether or not each clinician would be willing to recruit the example patients into future clinical trials.Aims
Methods
To investigate the correlations among cytokines and regulatory T cells (T-regs) in ankylosing spondylitis (AS) patients, and their changes after anti-tumour necrosis factor-α (TNF-α) treatment. We included 72 AS patients with detailed medical records, disease activity score (Bath Ankylosing Spondylitis Disease Activity Index), functional index (Bath Ankylosing Spondylitis Functional Index), and laboratory data (interleukin (IL)-2, IL-4, IL-10, TNF-α, interferon (IFN)-γ, transforming growth factor (TGF)-β, ESR, and CRP). Their peripheral blood mononuclear cells (PBMCs) were marked with anti-CD4, anti-CD25, and anti-FoxP3 antibodies, and triple positive T cells were gated by flow cytometry as T-regs. Their correlations were calculated and the changes after anti-TNF-α therapy were compared.Aims
Methods
We compared decompression alone to decompression with fusion surgery for lumbar spinal stenosis, with or without degenerative spondylolisthesis (DS). The aim was to evaluate if five-year outcomes differed between the groups. The two-year results from the same trial revealed no differences. The Swedish Spinal Stenosis Study was a multicentre randomized controlled trial with recruitment from September 2006 to February 2012. A total of 247 patients with one- or two-level central lumbar spinal stenosis, stratified by the presence of DS, were randomized to decompression alone or decompression with fusion. The five-year Oswestry Disability Index (ODI) was the primary outcome. Secondary outcomes were the EuroQol five-dimension questionnaire (EQ-5D), visual analogue scales for back and leg pain, and patient-reported satisfaction, decreased pain, and increased walking distance. The reoperation rate was recorded.Aims
Methods
The development of lumbar lordosis has been traditionally examined using angular measurements of the spine to reflect its shape. While studies agree regarding the increase in the angles during growth, the growth rate is understudied, and sexual dimorphism is debated. In this study, we used a novel method to estimate the shape of the lumbar curve (LC) using the landmark-based geometric morphometric method to explore changes in LC during growth, examine the effect of size and sex on LC shape, and examine the associations between angular measurements and shape. The study population included 258 children aged between 0 and 20 years (divided into five age groups) who underwent a CT scan between the years 2009 and 2019. The landmark-based geometric morphometric method was used to capture the LC shape in a sagittal view. Additionally, the lordosis was measured via Cobb and sacral slope angles. Multivariate and univariate statistical analyses were carried out to examine differences in shape between males and females and between the age groups.Aims
Methods
CRP is an acute-phase protein that is used as a biomarker to follow severity and progression in infectious and inflammatory diseases. Its pathophysiological mechanisms of action are still poorly defined. CRP in its pentameric form exhibits weak anti-inflammatory activity. The monomeric isoform (mCRP) exerts potent proinflammatory properties in chondrocytes, endothelial cells, and leucocytes. No data exist regarding mCRP effects in human intervertebral disc (IVD) cells. This work aimed to verify the pathophysiological relevance of mCRP in the aetiology and/or progression of IVD degeneration. We investigated the effects of mCRP and the signalling pathways that are involved in cultured human primary annulus fibrosus (AF) cells and in the human nucleus pulposus (NP) immortalized cell line HNPSV-1. We determined messenger RNA (mRNA) and protein levels of relevant factors involved in inflammatory responses, by quantitative real-time polymerase chain reaction (RT-qPCR) and western blot. We also studied the presence of mCRP in human AF and NP tissues by immunohistochemistry.Aims
Methods
The aims of this study were first, to determine if adding fusion to a decompression of the lumbar spine for spinal stenosis decreases the rate of radiological restenosis and/or proximal adjacent level stenosis two years after surgery, and second, to evaluate the change in vertebral slip two years after surgery with and without fusion. The Swedish Spinal Stenosis Study (SSSS) was conducted between 2006 and 2012 at five public and two private hospitals. Six centres participated in this two-year MRI follow-up. We randomized 222 patients with central lumbar spinal stenosis at one or two adjacent levels into two groups, decompression alone and decompression with fusion. The presence or absence of a preoperative spondylolisthesis was noted. A new stenosis on two-year MRI was used as the primary outcome, defined as a dural sac cross-sectional area ≤ 75 mm2 at the operated level (restenosis) and/or at the level above (proximal adjacent level stenosis).Aims
Methods
With resumption of elective spine surgery services in the UK following the first wave of the COVID-19 pandemic, we conducted a multicentre British Association of Spine Surgeons (BASS) collaborative study to examine the complications and deaths due to COVID-19 at the recovery phase of the pandemic. The aim was to analyze the safety of elective spinal surgery during the pandemic. A prospective observational study was conducted from eight spinal centres for the first month of operating following restoration of elective spine surgery in each individual unit. Primary outcome measure was the 30-day postoperative COVID-19 infection rate. Secondary outcomes analyzed were the 30-day mortality rate, surgical adverse events, medical complications, and length of inpatient stay.Aims
Methods
The aim of this study was to identify factors associated with poor outcome following coccygectomy on patients with chronic coccydynia and instability of the coccyx. From the Danish National Spine Registry, DaneSpine, 134 consecutive patients were identified from a single centre who had coccygectomy from 2011 to 2019. Patient demographic data and patient-reported outcomes, including pain measured on a visual analogue scale (VAS), Oswestry Disability Index (ODI), EuroQol five-dimension five-level questionnaire, and 36-Item Short-Form Health Survey questionnaire (SF-36) were obtained at baseline and at one-year follow-up. Patient satisfaction was obtained at follow-up. Regression analysis, including age, sex, smoking status, BMI, duration of symptoms, work status, welfare payment, preoperative VAS, ODI, and SF-36 was performed to identify factors associated with dissatisfaction with results at one-year follow-up.Aims
Methods
Non-coding microRNA (miRNA) in extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) may promote neuronal repair after spinal cord injury (SCI). In this paper we report on the effects of MSC-EV-microRNA-381 (miR-381) in a rodent model of SCI. In the current study, the luciferase assay confirmed a binding site of bromodomain-containing protein 4 (BRD4) and Wnt family member 5A (WNT5A). Then we detected expression of miR-381, BRD4, and WNT5A in dorsal root ganglia (DRG) cells treated with MSC-isolated EVs and measured neuron apoptosis in culture by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. A rat model of SCI was established to detect the in vivo effect of miR-381 and MSC-EVs on SCI.Aims
Methods
Inflammatory response plays a pivotal role in the pathophysiological process of intervertebral disc degeneration (IDD). A20 (also known as tumour necrosis factor alpha-induced protein 3 (TNFAIP3)) is a ubiquitin-editing enzyme that restricts nuclear factor-kappa B (NF-κB) signalling. A20 prevents the occurrence of multiple inflammatory diseases. However, the role of A20 in the initiation of IDD has not been elucidated. The aim of the study was to investigate the effect of A20 in senescence of TNF alpha (TNF-α)-induced nucleus pulposus cells (NPCs). Immunohistochemical staining was performed to observe the expression of A20 in normal and degenerated human intervertebral discs. The NPCs were dissected from the tail vertebrae of healthy male Sprague-Dawley rats and were cultured in the incubator. In the experiment, TNF-α was used to mimic the inflammatory environment of IDD. The cell viability and senescence were examined to investigate the effect of A20 on TNF-α-treated NPCs. The expression of messenger RNA (mRNA)-encoding proteins related to matrix macromolecules (collagen II, aggrecan) and senescence markers (p53, p16). Additionally, NF-κB/p65 activity of NPCs was detected within different test compounds.Aims
Methods
In order to elucidate the influence of sympathetic nerves on
lumbar radiculopathy, we investigated whether sympathectomy attenuated
pain behaviour and altered the electrical properties of the dorsal
root ganglion (DRG) neurons in a rat model of lumbar root constriction. Sprague-Dawley rats were divided into three experimental groups.
In the root constriction group, the left L5 spinal nerve root was
ligated proximal to the DRG as a lumbar radiculopathy model. In
the root constriction + sympathectomy group, sympathectomy was performed
after the root constriction procedure. In the control group, no
procedures were performed. In order to evaluate the pain relief
effect of sympathectomy, behavioural analysis using mechanical and
thermal stimulation was performed. In order to evaluate the excitability
of the DRG neurons, we recorded action potentials of the isolated
single DRG neuron by the whole-cell patch-clamp method.Objectives
Methods
