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Background: Tryptophan 2,3-dioxygenase (TDO2) is the primary enzyme that catabolizes tryptophan to kynurenine. Numerous studies have suggested that TDO2 is involved in inflammation-related diseases. However, its role in osteoarthritis (OA) has not yet been investigated. The aim of the present study was to explore the levels of TDO2 in the synovium and synovial fluid (SF) of patients with OA and its correlation with clinical manifestations and levels of pro-inflammatory cytokines.  METHODS : Synovium and SF samples were collected from patients with OA and patients with joint trauma (controls) during surgery. An enzyme-linked immunosorbent assay (ELISA) was used to measure TDO2, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) levels in the synovium and SF. Diagnostic performance of TDO2 in the synovium to discriminate between controls and OA patients was assessed using receiver operating characteristic (ROC) curve analysis. Correlations between TDO2 levels, OA clinical features, and pro-inflammatory cytokines were evaluated using Pearson correlation analysis. Effects of IL-1β or TNF-α stimulation on TDO2 expression in OA-fibroblast-like synoviocytes (OA-FLS) were also examined.Results: The levels of TDO2, IL-1β, and TNF-α in the synovium of patients with OA were found to be significantly higher than those in controls. ROC curve analysis revealed an area under the curve (AUC) of 0.800 with 64.3% sensitivity and 85.0% specificity of TOD2 in the synovium, which enabled discriminating patients with OA from controls. Moreover, protein expression of TDO2 was upregulated to a greater extent in OA-FLS than in normal synovial fibroblasts (NSF). Furthermore, the levels of TDO2 showed significantly positive correlation with IL-1β and TNF-α levels in the synovium and SF. TDO2 levels in the synovium were also positively correlated with the Kellgren-Lawrence score. Additionally, TDO2 protein expression was significantly increased in IL-1β‒ or TNF-α‒stimulated OA-FLS than in control FLS.Conclusion: These data indicate that highTDO2 levels in the synovium can be correlated with pro-inflammatory cytokines and severity of OA. [ABSTRACT FROM AUTHOR]

The expansion and maintenance of the NPMSC (nucleus pulposus mesenchymal stem cell) phenotype are considered as potential therapeutic tools for clinical applications in intervertebral disc tissue engineering and regenerative medicine. However, the harsh microenvironment within the intervertebral disc is the main limitation of its regeneration. The osmolarity of the intervertebral disc is higher than that of other tissues, which has an important influence on the biological characteristics of NPMSCs. In this study, we observed the effect of different osmolarities on the biological characteristics of human normal NPMSCs cultured in vitro and explored the role of osmolarity in intervertebral disc degeneration. Our data demonstrated that the change in osmotic pressure has an important effect on the biological activity of NPMSCs, and this effect may occur through the P16INK4A/Rb pathway. This study provides a theoretical basis for the future treatment of intervertebral disc degeneration. [ABSTRACT FROM AUTHOR]

Degenerative cervical myelopathy is a progressive neurodegenerative disease, that has become increasingly prevalent in the aging population worldwide. The current study determined the factors affecting degeneration in the sensorimotor tract with degenerative cervical myelopathy and its relationship with brain structure. We divided patients into hyperintensity (HS) and non-hyperintensity (nHS) groups and measured the fractional anisotropy and apparent diffusion coefficients of the lateral corticospinal tract (CST), fasciculus gracilis and fasciculus cuneatus (FGC). Voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) techniques were used to estimate brain structure changes. Correlation of the modified Japanese Orthopaedic Association (mJOA) score, light touch, pinprick, motor score, and fractional anisotropy (FA) ratios of the CST at different levels were analyzed. Compared to healthy controls, the FA ratios of CST in the HS and nHS groups were decreased at all levels, and the apparent diffusion coefficient (ADC) ratio was increased only at C4/5 levels in the HS group. The FA ratio of FGC was decreased at the C3/4 and C4/5 levels in the HS group and only decreased at the C4/5 level in the nHS group. The ADC ratio was decreased only at the C4/5 level in the HS group. VBM analysis revealed that the volume of the precentral gyrus, postcentral gyrus, and paracentral lobule increased in patients compared to controls. TBSS analysis found no statistical significance between the sensory and motor tracts in white matter. The volume of clusters in HS and nHS groups negatively correlated with the C1/2 FA ratio of the CST. The results showed that the degeneration distance of the CST was longer than the FGC, and the degeneration distance was related to the degree of compression and spinal cord damage. Structural compensation and the neurotrophin family may lead to enlargement of the brain. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) often causes neuronal and axonal damage, resulting in permanent neurological impairments. Mesenchymal stem cells (MSCs) and extracellular vesicles (EVs) are promising treatments for SCI. However, the underlying mechanisms remain unclear. Herein, we demonstrated that EVs from bone marrow-derived MSCs promoted the differentiation of neural stem cells (NSCs) into the neurons and outgrowth of neurites that are extending into astrocytic scars in SCI rats. Further study found that let-7a-5p exerted a similar biological effect as MSC-EVs in regulating the differentiation of NSCs and leading to neurological improvement in SCI rats. Moreover, these MSC-EV-induced effects were attenuated by let-7a-5p inhibitors/antagomirs. When investigating the mechanism, bioinformatics predictions combined with western blot and RT-PCR analyses showed that both MSC-EVs and let-7a-5p were able to downregulate the expression of SMAD2 by inhibiting HMGA2. In conclusion, MSC-EV-secreted let-7a-5p promoted the regrowth of neurons and improved neurological recovery in SCI rats by targeting the HMGA2/SMAD2 axis. [ABSTRACT FROM AUTHOR]

Background: The leukocyte esterase (LE) strip is considered as a helpful method to detect infection, which might be influenced by other inflammatory diseases. This study aims to explore whether the centrifugation of synovial fluid could influence the positive result of LE strip caused by inflammatory arthritis during the diagnosis of periprosthetic joint infection (PJI). Methods: From March 2016 to December 2018, 64 patients who were diagnosed as PJI or aseptic arthritis and another 20 patients with inflammatory arthritis were enrolled in our study. After synovial fluid samples were obtained, the LE strip test was performed with and without centrifugation. Then clinicians read the color changes 3 min after the samples were dropped and classify the results based on the instruction of strip. The differences between septic and aseptic arthritis patients and septic and inflammatory arthritis patients were analyzed. Results: Among the included 21 PJI samples, 19 of them showed positive results (++) of LE strip before centrifugation. After centrifugation, two samples changed from two-positive (++) to one-positive (+), which is also considered as positive. Before centrifugation, 29 of the LE strip tests in the aseptic arthritis group (43 samples included) were ++ or +. After centrifugation, 16 of the samples yielded negative results. Among 20 samples with inflammatory arthritis, LE strip of 18 samples were positive (++ or +) before centrifugation, among which only 3 samples remained as positive after centrifugation. Conclusion: LE strip test results could be influenced by inflammatory arthritis during the diagnosis of PJI. Centrifugation should be performed for LE strip tests to determine whether the result is a true positive or a false positive influenced by inflammatory arthritis. [ABSTRACT FROM AUTHOR]

Numerous studies have demonstrated the therapeutic effect of bone mesenchymal stem cells on spinal cord injury (SCI), especially on neural stem cells (NSCs). However, the predominant mechanisms of bone mesenchymal stem cells (BMSCs) are unclear. Recently, some researchers have found that paracrine signaling plays a key role in the therapeutic capacity of BMSCs and emphasized that the protective effect of BMSCs may be due to paracrine factors. In this study, we aimed to investigate the potential mechanisms of BMSCs to protect NSCs. NSCs were identified by immunocytochemistry. The oxidative stress environment was simulated by H2O2 (50, 100, 200 μM) for 2 h. The apoptotic rate of the NSCs was detected via flow cytometry. Lactate dehydrogenase (LDH), malondialdehyde (MDA), and superoxide dismutase (SOD) activity were evaluated via corresponding assay kits. Western blot was used to detect the expressions of Notch1, HES1, caspase‐3, cleave caspase‐3, Bax, and Bcl‐2. We found that H2O2 could significantly induce the apoptosis of NSCs, increase LDH, MDA levels, and decrease SOD activity by activating the Notch1 signaling pathway. DAPT (the specific blocker of Notch1) and BMSC‐conditioned medium (BMSC‐CM) could significantly prevent the apoptotic effect and oxidative stress injury on NSCs that were treated with H2O2. We also revealed that BMSC‐CM could decrease the expression of Notch1, Hes1, cleave caspase‐3, Bax, and increases the expression of Bcl‐2 in NSCs, which was induced by H2O2. These results have revealed that BMSC‐CM can neutralize the effect against oxidative stress injury on the apoptosis of NSCs by inhibiting the Notch1 signaling pathway. [ABSTRACT FROM AUTHOR]

The endogenous spinal cord ependymal cells (SCECs), which form the central canal (CC), are critically involved in proliferation, differentiation and migration after spinal cord injury (SCI) and represents a repair cell source in treating SCI. Previously, we reported that BAF45D is expressed in the SCECs and the spinal cord neurons in adult mice and knockdown of BAF45D fail to induce expression of PAX6, a neurogenic fate determinant, during early neural differentiation of human embryonic stem cells. However, the effects of SCI on expression of BAF45D have not been reported. The aim of this study is to explore the expression and potential role of BAF45D in rat SCI model. In this study, adult rats were randomly divided into intact, sham, and SCI groups. We first explored expression of BAF45D in the SCECs in intact adult rats. We then explored SCI-induced loss of motor neurons and lesion of neurites in the anterior horns induced by the SCI. We also investigated whether the SCI-induced lesions in SCECs are accompanied by the motor neuron lesions. Finally, we examined the effect of BAF45D knockdown on cell growth in neuro2a cells. Our data showed that BAF45D is expressed in SCECs, neurons, and oligodendrocytes but not astrocytes in the spinal cords of intact adult rats. After SCI, the structure of CC was disrupted and the BAF45D-positive SCEC-derivatives were decreased. During the early stages of SCI, when shape of CC was affected but there was no disruption in circular structure of the SCECs, it was evident that there was a significant reduction in the number of neurites and motor neurons in the anterior horns compared with those of intact rats. In comparison, a complete loss of SCECs accompanied by further loss of motor neurons but not neurites was observed at the later stage. BAF45D knockdown was also found to inhibit cell growth in neuro2a cells. These results highlight the decreased expression of BAF45D in SCI-injured SCECs and the potential role of BAF45D downregulation in development of neuronal lesion after SCI in adult rats. [ABSTRACT FROM AUTHOR]

Purpose: To compare diffusion tensor imaging (DTI) parameters of the spinal cord between patients with cervical spondylotic myelopathy (CSM) and normal subjects, and investigate their significance in the clinical diagnosis, surgical planning and post-operative evaluation of CSM.Methods: Routine sequence magnetic resonance imaging (MRI) and DTI scans were performed in 50 normal subjects and 60 cases of CSM with 3.0-T MR. DTI images, apparent diffusion coefficient (ADC) and fractional anisotropy (FA) colormaps corresponding to spinal cord cross-sections were obtained. The spinal cord function of CSM patients was measured using modified Japanese Orthopaedic Association (mJOA) scoring and Nurick grade at different times. The changes in DTI parameters and their correlation with spinal cord function scores were analysed by SPSS 19.Results: There were significant differences in DTI parameters of the spinal cord between normal subjects and patients with CSM (ADC: 1.119 ± 0.087 vs. 1.395 ± 0.091, P < 0.01; FA: 0.661 ± 0.057 vs. 0.420 ± 0.080, P < 0.01). The FA values at the maximal compression level of the spinal cord in the patients with CSM were significantly associated with the mJOA score pre-operatively, 1 week, and 1, 3 and 6 months post-operatively, with Pearson's correlation coefficients of 0.58 (P < 0.01), 0.53 (P < 0.05), and 0.51 (P < 0.05), 0.54 (P < 0.05) and 0.55 (P < 0.05), respectively. However, the FA values were significantly negatively associated with the Nurick grade, with Pearson's correlation coefficients of - 0.40 (P < 0.05), - 0.39 (P < 0.05), and -0.41 (P < 0.05), - 0.45 (P < 0.05) and - 0.44 (P < 0.05), respectively.Conclusions: DTI may play a significant role in diagnosing and predicting the development of CSM. These slides can be retrieved under Electronic Supplementary Material. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a highly prevalent disease, which is associated with extracellular matrix degradation and cell death in articular cartilage. The aim of the present study was to identify whether tetrahydrohyperforin (IDN5706) ameliorates the degeneration of articular cartilage and affects autophagy in OA. The rat model of experimental OA was induced by intra-articular injection of collagenase solution. IDN5706 was administered intragastrically to rats for 6 weeks. Histopathological changes in articular cartilage were examined using hematoxylin and eosin (H&E) and safranin O staining, and Mankin scoring systems. The effect of IDN5706 on autophagy was examined using western blotting. ELISA was performed to detect cartilage inflammation. H&E and safranin O staining, Mankin scores, and electron microscopy indicated that IDN5706 could lessen the degeneration of articular cartilage in OA rats. In addition, western blotting revealed that IDN5706 treatment may activate the suppressed autophagy in OA rats. In conclusion, the present study demonstrated that IDN5706 was able to reduce the severity of experimental OA, alleviate the degeneration of articular cartilage, and affect autophagy in OA model rats. [ABSTRACT FROM AUTHOR]

Objectives: In this study, we aimed to investigate the effect of bone mesenchymal stem cells (BMSCs) conditioned medium on BMP4-induced activation of the Smad signaling pathway during the process of neural stem cells differentiation. Methods: We designed four experimental groups: (A) control group, (B) BMP-4 treatment group, (C) BMSC-CM group, and (D) BMSC-CM (BMSC-conditioned medium) combined with BMP-4 group. The expression of microtube-associated protein-2 (MAP-2) detected by immunocytochemical staining and western blot. The expression of glial fibrillary acidic protein (GFAP) and BMP receptors (BMPRII and BMPRIa) was determined by western blot, while SMAD1/5/8 and SMAD6 mRNA expression was detected by quantitative real-time polymerase chain reaction (Q-RT-PCR). Results: We found that the expression of microtube-associated protein-2 (MAP-2) increased in group B compared to group A. In group C, the expression of GFAP was increased and the expression of MAP-2 was decreased compared to group A. This phenomenon was weaker in group D. We also demonstrated that BMSC-CM could inhibit the activation of BMP signaling by downregulating the expression of BMPRII and BMPRIa proteins. Moreover, BMSC-CM could upregulate the expression of Smad6 mRNA and inhibit the activation of Smad1/5/8 mRNA. Conclusion: These observations suggest that BMSC-CM could neutralize the effect of BMP-4 on the differentiation of NSCs by upregulating the expression of Smad6 and decrease the expression of GFAP by inhibiting the BMP-4-SMAD1/5/8 signaling pathway, conversely increasing the generation of neurons. [ABSTRACT FROM AUTHOR]

People whom the editor would like to thank for their contribution in reviewing papers submitted to periodical are presented which includes Aboelnour Mohamed, Abraham Vineet and Addosooki Ahmad.

Purpose: To compare volume-occupying rate of cervical spinal canal between patients with cervical spondylotic myelopathy (CSM) and normal subjects, and to investigate its significance in cervical spine disease. Methods: Spiral computed tomography (CT) scan (C4-C6 cervical spine unit) was performed in 20 normal subjects and 36 cases of CSM at a neutral position, and data were transferred to the Advantage Workstation Version 4.2 for assessment. Bony canal area and fibrous canal area in each cross section, and sagittal diameters of cervical spinal canal and cervical spinal body were measured. Volume-occupying rate of cervical spinal canal was calculated using MATLAB. Cervical spinal canal ratio and effective cervical spinal canal ratio were calculated, and Japanese Orthopaedic Association score was used to assess cervical spinal cord function. Results: Volume-occupying rate of cervical spinal canal at a neutral position was significantly higher in CSM patients as compared to normal subjects ( P < 0.01). There was no correlation between cervical spinal canal ratio and JOA score in CSM patients, with a Pearson's correlation coefficient of 0.171 ( P > 0.05). However, sagittal diameter of secondary cervical spinal canal, effective cervical spinal canal ratio and volume-occupying rate of cervical spinal canal were significantly associated to JOA score, with Pearson's coefficient correlations of 0.439 ( P < 0.05), 0.491 ( P < 0.05) and −0.613 ( P < 0.01), respectively. Conclusions: Volume-occupying rate of cervical spinal canal is an objective reflection of compression on cervical spine and spinal cord, and it is associated with cervical spinal cord function. These suggest that it may play a significant role in predicting the development of CSM. [ABSTRACT FROM AUTHOR]

Background: Cortical bone trajectory (CBT) has been well-known in spine surgery for obtaining improved fixation while minimizing soft tissue dissection. This study was designed to compare the bone mineral density (BMD) between the CBT and traditional trajectory (TT) by using Hounsfield unit (HU) values and identify the ideal decades of patients and the suitable lumbar segments using this CBT technology from a radiological standpoint. Methods: Patients were selected randomly from an institutional database based on age (evenly distributed by a decade of life) and gender. A total of 240 healthy patients had a computed tomography (CT) scan of the chest, abdomen, and pelvis. For each patient, axial slices of every vertebra were cut in two planes: one horizontal to the pedicle representing the plane wherein pedicle screws were inserted using the TT and the other in a caudocranial plane representing the plane wherein pedicle screws were inserted using the CBT. For each trajectory, a region of interest (ROI) was selected within the area wherein the screws were inserted. A CT number (HU values) was then calculated within each ROI to represent bone density. Results: HU values measured at the ROI of CBT were significantly greater than those of the traditional pedicle screw in all age groups, and the specific value (ratio of the HU values of CBT/the HU values of TT) between CBT and TT was 1.92. A significant difference was observed between male and female. The HU values of CBT and TT of males were generally higher than those of females (males: CBT/TT 1.89 ± 0.45; Females: CBT/TT 1.95 ± 0.47). The specific value in HU values significantly increased with increasing age (p = 0.000) and cauda lumbar level (p = 0.000) in males and females. Conclusion: BMD, as measured by HU values for the ROI of the CBT screw, was significantly greater than that of the traditional pedicle screw, especially in old patients and cauda lumbar segments. [ABSTRACT FROM AUTHOR]