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
The principal of “function priority, early rehabilitation, and return to sports” is now the goal for sports injury rehabilitation. Neuromuscular electrical stimulation for anterior cruciate ligament (ACL) reconstruction is a rising procedure for early rehabilitation. This paper systematically assessed the effects of neuromuscular electrical stimulation on postoperative ACL reconstruction to provide guidance for physiotherapist and patient when designing a suitable rehabilitation protocol. To evaluate the interventional outcomes of neuromuscular electrical stimulation following ACL reconstruction, we searched PubMed, EMbase, the Cochrane Library, Web of Science and CNKI to collect all randomized controlled trials (RCTs) comparing the effects with neuromuscular electrical stimulation and without intervention on rehabilitation after ACL reconstruction up to January 30, 2022. Two investigators independently performed literature screening, data extraction, bias assessment of risk, and used RevMan 5.3 software to conduct a meta-analysis. A total of six RCTs were included, and the results showed that the use of neuromuscular electrical stimulation after anterior cruciate ligament reconstruction significantly improved the International Knee Documentation Committee (IKDC) scores (MD 6.33, 95% CI [-0.43, 12.22]; I2 = 66%; p = 0.040), the Lysholm score (MD 7.94, 95% CI [6.49, 9.39]; I2 = 89%; p < 0.001), and the range of motion (ROM) (MD 9.99, 95% CI [7.97, 12.02]; I2 = 81%; p < 0.001) in the knees when compared to the control group without using neuromuscular electrical stimulation. Existing evidence show that neuromuscular electrical stimulation is beneficial for early rehabilitation after ACL reconstruction. The use of neuromuscular electrical stimulation is encouraged in the design of rehabilitation protocol. However, due to the limited number of RCT studies and the small sample size, further multi-center RCTs with more participants are needed for a higher-level evidence.
Gap junction intercellular communication (GJIC) in osteocytes is impaired by oxidative stress, which is associated with age-related bone loss. Ageing is accompanied by the accumulation of advanced oxidation protein products (AOPPs). However, it is still unknown whether AOPP accumulation is involved in the impairment of osteocytes’ GJIC. This study aims to investigate the effect of AOPP accumulation on osteocytes’ GJIC in aged male mice and its mechanism. Changes in AOPP levels, expression of connexin43 (Cx43), osteocyte network, and bone mass were detected in 18-month-old and three-month-old male mice. Cx43 expression, GJIC function, mitochondria membrane potential, reactive oxygen species (ROS) levels, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation were detected in murine osteocyte-like cells (MLOY4 cells) treated with AOPPs. The Cx43 expression, osteocyte network, bone mass, and mechanical properties were detected in three-month-old mice treated with AOPPs for 12 weeks.Aims
Methods
The emerging of non-fusion surgery is aimed to solve the long-term complication of fusion surgery that may bring the adjacent disc degeneration. Among several kinds of artificial discs developed in these years, the majority in the market is Prodisc-L (Synthes Inc.) which is designed with the purpose to restore the motions including anteroposterior translation, lateral bending, and axial rotation. These is also one artificial disc called Physio-L (Nexgen Spine) which were hyper-elastic material (Polycarbonate Polyurethanes) and is designed to restore the motions maintioned above plus axial loading. The concept of using hyper-elastic material as disc is to mimic the material properties of intervetebral discs so that this disc both absorb the axial loading and also restore the physiological range of motion. Few studies focused on the biomechanical behavior of hyper-elastic artificial discs have yet been reported. Therefore, the purpose of this study is to compare the biomechanical behavior between Prodisc-L and Physio-L. A validated three-dimensional finite element model of the L1-L5 lumbar intact spine was used in this study with ANSYS software [Fig.1]. Total disc replacement surgery, partial discectomy, total nuclectomy and removal of the anterior longitudinal ligament were performed at the L3/L4 segment of this intact model, and the Prodisc-L and Physio-L was implanted into L3/L4 segment, respectively. In addition, hyper-elastic materials adopted by Physio-L are usually categorized by their hardness into soft and hard [Fig.2]. Therefore, two kinds of Physio-L were studied. A 400 N follower load and a 10 N-m moment were applied to the intact model to obtain four physiological motions as comparison baseline. The implanted models were subjected to 400 N follower load and specific moments in accordance with the hybrid test method. For the Prodisc-L model in the surgical segment, the range of motion (ROM) varied by -26%, +17%, -0.01%, and -0.04% in flexion, extension, lateral bending, and axial rotation, respectively, as compared to intact model [Fig.3]. For the Physio-L (soft) model, ROM varied by +10%, +8%, +3%, and +19% in four physiological motions, respectively. For the physio-L (hard) model, ROM varied by +1%, +8%, +1%, and +11% in four physiological motions, respectively. For the Prodisc-L model in the adjacent segments, ROM varied by +4% ∼ +10%, -2% ∼ -5%, -1% ∼ -4%, and +1% ∼ -2% in four physiological motions, respectively. For the Physio-L (soft) model, ROM varied by 0% ∼ -5%, -2% ∼ -5%, -0% ∼ -5%, and -9% ∼ -11% in four physiological motions, respectively. For the physio-L (hard) model, ROM varied by +4% ∼ -2%, +8% ∼ -5%, +1 ∼ -5%, and +11% ∼ -6% in four physiological motions, respectively. As seemed in the simulation, the behavior of Physio-L (both soft and hard) is similar to that of intact model under flexion and extension, but not in axial rotation. In addition, Physio-L (hard) model is more similar to intact model as compared to Physio-L (soft) model.