ABSTRACT
Functional and pathological recovery after spinal cord injury (SCI) is often incomplete due to the limited regenerative capacity of the central nervous system (CNS), which is further impaired by several mechanisms that sustain tissue damage. Among these, the chronic activation of immune cells can cause a persistent state of local CNS inflammation and damage. However, the mechanisms that sustain this persistent maladaptive immune response in SCI have not been fully clarified yet. In this study, we integrated histological analyses with proteomic, lipidomic, transcriptomic, and epitranscriptomic approaches to study the pathological and molecular alterations that develop in a mouse model of cervical spinal cord hemicontusion. We found significant pathological alterations of the lesion rim with myelin damage and axonal loss that persisted throughout the late chronic phase of SCI. This was coupled by a progressive lipid accumulation in myeloid cells, including resident microglia and infiltrating monocyte-derived macrophages. At tissue level, we found significant changes of proteins indicative of glycolytic, tricarboxylic acid cycle (TCA), and fatty acid metabolic pathways with an accumulation of triacylglycerides with C16:0 fatty acyl chains in chronic SCI. Following transcriptomic, proteomic, and epitranscriptomic studies identified an increase of cholesterol and m6A methylation in lipid-droplet-accumulating myeloid cells as a core feature of chronic SCI. By characterizing the multiple metabolic pathways altered in SCI, our work highlights a key role of lipid metabolism in the chronic response of the immune and central nervous system to damage.
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OBJECTIVE: In a previous study, we proved that an experienced urologist is more likely to adapt to the Hugo RAS system. Based on this, we further examine various parameters in this study. Parameters included in this study consisted of console time, functional outcomes, and oncological outcomes. MATERIALS AND METHODS: A total of 60 patients who underwent robot-assisted radical prostatectomy (RARP) performed by a single surgeon using the da Vinci (DV) system (n = 30) or the Hugo RAS system (n = 30) between March 2023 and August 2023 were included in the analysis. The intraoperative operative time was categorized into vesicourethral anastomosis time and overall console time. Functional and oncological outcomes were documented at the 1st and 3rd postoperative months. Parametric and non-parametric methods were adopted after checking skewness and kurtosis, and an α value of 5% was used to determine the significance. RESULTS: The vesicourethral anastomosis time was significantly lengthened (Hedge's g: 0.87; 95% confidence interval (CI): 0.34-1.39; J factor = 0.987). However, the overall console time was not affected. The functional (postoperative 3rd month: p = 0.130) and oncological outcomes (postoperative 3rd month: p = 0.103) were not significantly different. We also found that the adverse effect on surgical specimens and positive surgical margins was not affected (p = 0.552). CONCLUSION: During the process of adaptation, although intricate motions (such as the vesicourethral anastomosis time) would be lengthened, the overall console time would not change remarkably. In this process, the functional and oncological outcomes would not be compromised. This encourages urologists to adopt the Hugo RAS system in RARP if they have previous experiences of using the DV system, since their trifecta advantage would not be compromised.
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Osteoblast apoptosis plays an important role in age-related bone loss and osteoporosis. Our previous study revealed that advanced oxidation protein products (AOPPs) could induce nicotinamide adenine dinucleotide phosphate oxidase (NOX)-derived reactive oxygen species (ROS) production, cause mitochondrial membrane potential (ΔΨm) depolarization, trigger the mitochondria-dependent intrinsic apoptosis pathway, and lead to osteoblast apoptosis and ultimately osteopenia and bone microstructural destruction. In this study, we found that AOPPs also induced mitochondrial ROS (mtROS) generation in osteoblastic MC3T3-E1 cells, which was closely related to NOX-derived ROS, and aggravated the oxidative stress condition, thereby further promoting apoptosis. Removing excessive ROS and damaged mitochondria is the key factor in reversing AOPP-induced apoptosis. Here, by in vitro studies, we showed that rapamycin further activated PINK1/Parkin-mediated mitophagy in AOPP-stimulated MC3T3-E1 cells and significantly alleviated AOPP-induced cell apoptosis by eliminating ROS and damaged mitochondria. Our in vivo studies revealed that PINK1/Parkin-mediated mitophagy could decrease the plasma AOPP concentration and inhibit AOPP-induced osteoblast apoptosis, thus ameliorating AOPP accumulation-related bone loss, bone microstructural destruction and bone mineral density (BMD) loss. Together, our study indicated that therapeutic strategies aimed at upregulating osteoblast mitophagy and preserving mitochondrial function might have potential for treating age-related osteoporosis.
Subject(s)
Advanced Oxidation Protein Products , Mitophagy , Advanced Oxidation Protein Products/metabolism , Apoptosis , Osteoblasts/metabolism , Protein Kinases/metabolism , Reactive Oxygen Species/metabolism , Ubiquitin-Protein Ligases/metabolism , Animals , MiceABSTRACT
BACKGROUND CONTEXT: It is commonly believed that decreased bone quality would lead to endplate degeneration and arthritic changes in the facet joints, and thus accelerated disc degeneration (DD). However, some more detailed studies of vertebral bone structure have found that bone mineral density (BMD) in the vertebral body is increased rather than decreased in moderate or greater disc degeneration. The relationship between BMD and DD still needs further study. MRI-based vertebral bone quality scores have been shown to be effective in reflecting BMD, rendering a new way to evaluate the changes of vertebral body bone with DD using MRI alone. PURPOSE: To evaluate MRI-based vertebral bone quality and Pfirrmann grades in patients with lumbar spinal stenosis or disc herniation, and to identify if DD is associated with denser bone around the endplate. STUDY DESIGN/SETTING: A single-center, retrospective cohort study. PATIENT SAMPLE: A total of 130 patients with lumbar disc herniation and lumbar spinal stenosis from January 2019 to November 2020 who had a complete dual-energy X-ray absorptiometry scan and noncontrast lumbosacral spine MRI data. OUTCOME MEASURES: The vertebral bone quality score (VBQ) and sub-endplate bone quality score (EBQ) was calculated as a ratio of the signal intensity of the vertebral bodies and sub-endplate regions to the signal intensity of the cerebrospinal fluid at L3 on the mid-sagittal T1-weighted MRI images, respectively. The Pfirrmann grades of the lumbar discs were assessed as well. METHODS: The age, gender, body mass index, and T-score of the lumbar spine of the patients were collected. The degeneration grades of the lumbar discs were evaluated according to the Pfirrmann classification. VBQ and EBQ were measured through T1-weighted lumbar MRI. The VBQ and EBQ scores were compared between cranial and caudal sides. The correlation between MRI-based bone quality and DD was calculated. A linear regression model was used to examine the association between DD and adjacent EBQ and VBQ. RESULTS: This study included 569 lumbar segments from 130 inpatients. Cranial and caudal EBQ decreased with the increase of the Pfirrmann grade. The discs with Pfirrmann grade 5 had significantly lower caudal EBQ than the discs with Pfirrmann grades 2, 3, and 4. In the osteoporosis patients, the Pfirrmann grades negatively correlated both with the cranial EBQ and caudal EBQ. Pfirrmann grade greater than 4 was an independent contributor to the cranial EBQ, whereas greater than 3 was an independent contributor to the caudal EBQ. CONCLUSIONS: Disc degeneration grades correlated with the EBQ but not with the VBQ. In patients with lumbar spinal stenosis or disc herniation, DD contributes to the denser bone in the sub-endplate, but not in the whole vertebral body.
Subject(s)
Intervertebral Disc Degeneration , Intervertebral Disc Displacement , Intervertebral Disc , Spinal Stenosis , Humans , Intervertebral Disc Degeneration/diagnostic imaging , Intervertebral Disc Displacement/complications , Intervertebral Disc Displacement/diagnostic imaging , Vertebral Body , Spinal Stenosis/diagnostic imaging , Retrospective Studies , Lumbar Vertebrae/diagnostic imaging , Magnetic Resonance Imaging/methodsABSTRACT
Bladder dysfunction is a common complication after chronic spinal cord injury (SCI). Patients may experience renal function loss, urinary tract infection (UTI), urolithiasis, bladder cancer, and even life-threatening events such as severe sepsis or renal failure. Suitable patient care may prevent UTI and urinary incontinence, decrease medication use, and preserve renal function. As the primary goal is to preserve renal function, management should be focused on facilitating bladder drainage, the avoidance of UTI, and the maintenance of a low intravesical pressure for continence and complete bladder emptying. Currently, several bladder management options are available to SCI patients: (1) reflex voiding; (2) clean intermittent catheterization; (3) indwelling catheterization. The target organ may be the bladder or the bladder outlet. The purposes of intervention include the following: (1) increasing bladder capacity and/or decreasing intravesical pressure; (2) increasing bladder outlet resistance; (3) decreasing bladder outlet resistance; (4) producing detrusor contractility; (5) urinary diversion. Different bladder management methods and interventions may have different results depending on the patient's lower urinary tract dysfunction. This review aims to report the current management options for long-term bladder dysfunction in chronic SCI patients. Furthermore, we summarize the most suitable care plans for improving the clinical outcome of SCI patients.
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Transinguinal preperitoneal (TIPP) single-layer mesh herniorrhaphy has been proven effective. Mesh manufacturers make either a single-unit, two-layer mesh design or a separate optional onlay with the pre-peritoneal mesh. For peace of mind, most surgeons still incorporate the optional onlay. This study evaluated any counterproductive effects of adding the onlay to single-layer TIPP mesh herniorrhaphy and compared the long-term efficacy. This prospective, single-surgeon, single-center, randomized trial compared two groups of 50 consecutive patients at a 1 to 1 ratio. The control group received a single-layer modified Kugel mesh in the preperitoneal space, while the study group received the optional onlay mesh in the inguinal canal with preperitoneal mesh placement. A single surgeon performed the same operation to place the preperitoneal mesh in both groups, the only difference being the placement of the optional onlay mesh in the study group. A blinded researcher performed post-operative interviews using a series of questions at 1, 3, 6, and 12 months after surgery, and another unblinded researcher organized and performed statistical analysis of the peri-operative and post-operative data. The primary endpoints included foreign body sensation, pain, and any other discomfort in the inguinal region following surgery; and the secondary endpoints included recurrence and any complications related to surgery. The patient demographics were similar between the two groups. The average follow-up period was 29 months. Two patients in the 1-layer group and one patient in the 2-layer group were lost to follow-up. Postoperative pain, numbness and soreness were similar between groups. No patients experienced a foreign body sensation after 3 months in the 1-layer group, while five patients still had a foreign body sensation at 12 months in the 2-layer group. No recurrence was noted in either group during the follow-up period. Adequate dissection of the preperitoneal space is the key to a successful single-layer TIPP herniorrhaphy. With decreased materials in the inguinal canal, single-layer TIPP has a lower rate of long-term postoperative discomfort without increasing the risk of future recurrence.Trial registration: ISRCTN 47111213.
Subject(s)
Foreign Bodies , Hernia, Inguinal , Foreign Bodies/complications , Hernia, Inguinal/surgery , Herniorrhaphy/adverse effects , Humans , Pain, Postoperative/etiology , Pain, Postoperative/prevention & control , Prospective Studies , Surgical Mesh/adverse effects , Treatment OutcomeABSTRACT
Macrophages and microglia play important roles in chronic neuroinflammation following spinal cord injury (SCI). Although macrophages and microglia have similar functions, their phagocytic and homeostatic abilities differ. It is difficult to distinguish between these two populations in vivo, but single-cell analysis can improve our understanding of their identity and heterogeneity. We conducted bioinformatics analysis of the single-cell RNA sequencing dataset GSE159638, identifying apolipoprotein E (APOE) as a hub gene in both macrophages and microglia in the subacute and chronic phases of SCI. We then validated these transcriptomic changes in a mouse model of cervical spinal cord hemi-contusion and observed myelin uptake, lipid droplets, and lysosome accumulation in macrophages and microglia following SCI. Finally, we observed that knocking out APOE aggravated neurological dysfunction, increased neuroinflammation, and exacerbated the loss of white matter. Targeting APOE and the related cholesterol efflux represents a promising strategy for reducing neuroinflammation and promoting recovery following SCI.
Subject(s)
Apolipoproteins E , Macrophages , Microglia , Neuroinflammatory Diseases , Spinal Cord Injuries , Animals , Apolipoproteins E/genetics , Apolipoproteins E/immunology , Computational Biology , Macrophages/immunology , Mice , Microglia/immunology , Neuroinflammatory Diseases/genetics , Neuroinflammatory Diseases/immunology , Spinal Cord Injuries/genetics , Spinal Cord Injuries/immunologyABSTRACT
Background: Despite advances in prognosis and treatment of lung adenocarcinoma (LADC), a notable non-small cell lung cancer subtype, patient outcomes are still unsatisfactory. New insight on novel therapeutic strategies for LADC may be gained from a more comprehensive understanding of cancer progression mechanisms. Such strategies could reduce the mortality and morbidity of patients with LADC. In our previous study, we performed cDNA microarray screening and found an inverse relationship between inhibitor of DNA binding 2 (Id2) expression levels and the invasiveness of LADC cells. Materials and Methods: To identify the functional roles of Id2 and its action mechanisms in LADC progression, we successfully established several Id2-overexpressing and Id2-silenced LADC cell clones. Subsequently, we examined in vitro the effects exerted by Id2 on cell morphology, proliferation, colony formation, invasive, and migratory activities and examined in vivo those exerted by Id2 on cell metastasis. The mechanisms underlying the action of Id2 were investigated using RNA-seq and pathway analyses. Furthermore, the correlations of Id2 with its target gene expression and clinical outcomes were calculated. Results: Our data revealed that Id2 overexpression could inhibit LADC cells' migratory, invasive, proliferation, and colony formation capabilities. Silencing Id2 expression in LADC cells reversed the aforementioned inhibitory effects, and knockdown of Id2 increased LADC cells' metastatic abilities in vivo. Bioinformatics analysis revealed that these effects of Id2 on cancer progression might be regulated by focal adhesion kinase (FAK) signaling and CD44/Twist expression. Furthermore, in online clinical database analysis, patients with LADC whose Id2 expression levels were high and FAK/Twist expression levels were low had superior clinical outcomes.Conclusion: Our data indicate that the Id2 gene may act as a metastasis suppressor and provide new insights into LADC progression and therapy.
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Cajanus cajan (L.) Millsp., known as pigeon pea, is one of the major grain legume crops of the tropical world. It recognizes as an ethnomedicine to possess various functions, such as helping in healing wound and cancer therapy. We investigated whether 95% ethanol extracts from C. cajan root (EECR) protect against methylglyoxal (MGO)-induced insulin resistance (IR) and hyperlipidemia in male Wistar rats and explored its possible mechanisms. The hypoglycemic potential of EECR was evaluated using α-amylase, α-glucosidase activities, and advanced glycation end products (AGEs) formation. For in vivo study, the rats were divided into six groups and orally supplemented with MGO except for Group 1 (controls). Group 2 was supplemented with MGO only, Group 3: MGO + metformin, Group 4: MGO + Low dose-EECR (L-EECR; 10 mg/kg bw), Group 5: MGO + Middle dose-EECR (M-EECR; 50 mg/kg bw), and Group 6: MGO + High dose-EECR (H-EECR; 100 mg/kg bw). EECR possessed good inhibition of α-glucosidase, α-amylase activities, and AGEs formation (IC50 = 0.12, 0.32, and 0.50 mg/mL), respectively. MGO significantly increased serum levels of blood glucose (GLU), glycosylated hemoglobin, homeostasis model assessment of IR, AGEs, lipid biochemical values, and atherogenic index, whereas EECR decreased these levels in a dose-dependent manner. EECR can also act as an insulin sensitizer, which significantly decreased (47%, P < 0.05) the blood GLU levels after intraperitoneal injection of insulin in the insulin tolerance tests. The hypoglycemic and antihyperlipidemic mechanisms of EECR are likely through several possible pathways including the inhibition of carbohydrate-hydrolyzing enzymes (α-glucosidase and α-amylase) and the enhancement of MGO-trapping effects on inhibition of AGEs formation.
Subject(s)
Cajanus , Diabetes Mellitus, Experimental , Animals , Cajanus/metabolism , Diabetes Mellitus, Experimental/drug therapy , Glycation End Products, Advanced/metabolism , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Hypolipidemic Agents/pharmacology , Hypolipidemic Agents/therapeutic use , Insulin , Magnesium Oxide , Male , Pyruvaldehyde/metabolism , Pyruvaldehyde/pharmacology , Rats , Rats, Wistar , alpha-Amylases , alpha-GlucosidasesABSTRACT
Background and objectives: NPS-1034 with a dual inhibitory effect on Met and Axl kinase receptors has exhibited therapeutic potential in previous models. However, no study on treating testicular cancer (TC) cell lines with NPS-1034 has been established. Materials and Methods: In this study, a series of in vitro examinations of the apoptotic effect induced by NPS-1034 in TC cell lines was conducted to clarify the molecular interactions involved. Results: A decrease in cell viability rate was observed following NPS-1034 treatment, as shown in the MTT assay. Induction of the apoptotic effect was observed in TC cells as the sub-G1 and Annexin-PI populations increased in a dose-dependent manner. The involvement of the tumor receptor necrosis factor receptor 1 (TNFR1) pathway was later determined by the proteome array and western blotting. A reduction in TNFR1 and NF-κB downstream protein expressions, an upregulation of cleaved caspase-3 and -7, and a downregulation of survivin and claspin all reassured the underlying mechanism of the TNFR1 involved in the apoptotic pathway induced by NPS-1034. Conclusions: Our findings provide evidence for a potential underlying TNFR1 pathway involved in NPS-1034 treatment. This study should offer new insights into targeted therapy for TC.
Subject(s)
NF-kappa B , Testicular Neoplasms , Apoptosis , Cell Death , Heterocyclic Compounds, 2-Ring , Humans , Male , Pyrazoles , Receptors, Tumor Necrosis Factor, Type I/pharmacology , Signal Transduction/physiology , Testicular Neoplasms/drug therapyABSTRACT
Neuroinflammation is recognized as a hallmark of spinal cord injury (SCI). Although neuroinflammation is an important pathogenic factor that leads to secondary injuries after SCI, neuroprotective anti-inflammatory treatments remain ineffective in the management of SCI. Moreover, the molecular signatures involved in the pathophysiological changes that occur during the course of SCI remain ambiguous. The current study investigated the proteins and pathways involved in C5 spinal cord hemi-contusion injury using a rat model by means of 4-D label-free proteomic analysis. Furthermore, two Gene Expression Omnibus (GEO) transcriptomic datasets, Western blot assays, and immunofluorescent staining were used to validate the expression levels and localization of dysregulated proteins. The present study observed that the rat models of SCI were associated with the enrichment of proteins related to the complement and coagulation cascades, cholesterol metabolism, and lysosome pathway throughout the acute and subacute phases of injury. Intriguingly, the current study also observed that 75 genes were significantly altered in both the GEO datasets, including ANXA1, C1QC, CTSZ, GM2A, GPNMB, and PYCARD. Further temporal clustering analysis revealed that the continuously upregulated protein cluster was associated with immune response, lipid regulation, lysosome pathway, and myeloid cells. Additionally, five proteins were further validated by means of Western blot assays and the immunofluorescent staining showed that these proteins coexisted with the F4/80+ reactive microglia and infiltrating macrophages. In conclusion, the proteomic data pertaining to the current study indicate the notable proteins and pathways that may be novel therapeutic targets for the treatment of SCI.
Subject(s)
Contusions/metabolism , Inflammation/metabolism , Neurons/metabolism , Spinal Cord Injuries/metabolism , Spinal Cord/metabolism , Animals , Computational Biology/methods , Disease Models, Animal , Immunity/physiology , Macrophages/metabolism , Male , Microglia/metabolism , Myeloid Cells/metabolism , Proteomics/methods , Rats , Rats, Sprague-Dawley , Signal Transduction/physiology , Up-Regulation/physiologyABSTRACT
Context: Considerable controversy exists over surgical procedures for ossification of the posterior longitudinal ligament (OPLL).Objective: The purpose of the meta-analysis was to compare the clinical outcome of anterior decompression and fusion (ADF) with laminoplasty (LAMP) in treatment of cervical myelopathy due to OPLL.Methods: PubMed, EMBASE and the Cochrane Register of Controlled Trials database were searched to identify potential clinical studies compared ADF with LAMP for cervical myelopathy owing to OPLL. We also manually searched the reference lists of articles and reviews for possible relevant studies. Thirteen studies with 1120 patients were included in our analysis. Subgroup analyses were performed by the canal occupying ratio of OPLL.Results: Overall, the mean preoperative Japanese Orthopaedic Association (JOA) score was similar between two groups. Compared with LAMP group, ADF group was higher at the mean postoperative JOA scores and mean recovery rate, reoperation rate, and longer at mean operation time. There was not significantly different in mean blood loss and complication rate between two groups. In subgroup analysis, ADF had a higher mean postoperative JOA score and recovery rate than LAMP in cases of OPLL with occupying ratios ≥ 50%, while those difference were not found in cases of OPLL with occupying ratios < 50%.Conclusion: ADF achieves better neurological improvement compared with LAMP in treatment of cervical myelopathy due to OPLL, especially in cases of OPLL with occupying ratios ≥ 50%. Complication rate is similar between two groups, but ADF can increase the risk of reoperation.
Subject(s)
Laminoplasty , Ossification of Posterior Longitudinal Ligament , Spinal Cord Diseases , Spinal Cord Injuries , Spinal Fusion , Cervical Vertebrae/surgery , Decompression, Surgical , Humans , Laminoplasty/adverse effects , Longitudinal Ligaments , Ossification of Posterior Longitudinal Ligament/surgery , Osteogenesis , Retrospective Studies , Spinal Cord Diseases/etiology , Spinal Cord Diseases/surgery , Spinal Fusion/adverse effects , Treatment OutcomeABSTRACT
PURPOSE: To put forward a method for earlier diagnosis of surgical site infection (SSI) after spinal surgery and identify the best cut-offs of the selective signs. METHODS: Ninety cases were prospectively collected in consecutive patients who underwent spinal surgery. The patients were divided into the SSI group and the normal group. White blood cell (WBC) count, lymphocyte count, serum amyloid A (SAA), procalcitonin (PCT) and C-reactive protein (CRP) were collected pre-operatively and at three andsix days post-operatively. Erythrocyte sedimentation rates (ESR) were acquired pre-operatively and at six days post-operatively. Body temperature (BT) was measured every day during hospitalisation. The conditions of the surgical sites were recorded at three and six days post-operatively. Differences of BT, the conditions of the wound and the values of the inflammatory markers between the two groups were studied. Finally, we used the receiver operating characteristic curve (ROC curve) to determine the best cut-offs of the selected signs. RESULTS: Of the 90 patients, SSI occurred in seven and five of them reached a definite diagnosis of SSI as their bacterial cultures were positive. Significant differences were found in CRP levels at three and six days post-operatively with a cut-off of > 59.4 mg/L and > 34.9 mg/L, respectively; ESR level at six days post-operatively with a cut-off of > 51.5 mm/h; PCT at three days post-operatively with a cut-off of > 0.11 ng/mL; and BT at three days post-operatively with a cut-off of > 37 °C. Also, examination of the wound is also an important sign of SSI. CONCLUSION: CRP, ESR and PCT are considered useful markers for earlier diagnosis of SSI. Combining the above markers with BT and the wound condition yields more accurate results.
Subject(s)
C-Reactive Protein , Surgical Wound Infection , Biomarkers , Blood Sedimentation , C-Reactive Protein/analysis , Humans , Leukocyte Count , Procalcitonin , ROC Curve , Surgical Wound Infection/diagnosis , Surgical Wound Infection/epidemiology , Surgical Wound Infection/etiologyABSTRACT
Interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, in particular, control the degeneration of articular cartilage, making them prime targets for osteoarthritis (OA) therapeutic strategies. Advanced oxidation protein products (AOPPs) are prevalent in numerous diseases. Our previous work demonstrates that intra-articular injections of AOPPs accelerate regression of cartilage in OA models. Whether AOPPs exist in the course of OA and their effects on TNF-α and IL-1ß expression in chondrocytes are still unclear. This study confirmed that AOPPs levels in human synovial fluid were positively associated with severity of OA. We also found AOPPs deposition in articular cartilage in anterior cruciate ligament transection (ACLT) induced rodent OA models. AOPPs increased expression of TNF-α and IL-1ß in chondrocytes in vitro, which was inhibited by pre-treatment with SB202190 (p38-MAPK inhibitor) or apocynin (NADPH oxidase inhibitor) or NOX4 knockdown by siRNAs. Subsequently, we further verified in vivo that exogenous injection of AOPPs in OA mice up-regulated expression of TNF-α and IL-1ß in cartilage, which was blocked by treatment with apocynin. In parallel, apocynin attenuated articular cartilage degeneration resulting in substantially lower OARSI scores. Specifically, apocynin reduced NOX4, p-P38, TNF-α and IL-1ß and increased collagen II and glycosaminoglycan (GAG). This study demonstrated that AOPPs increased expression of TNF-α and IL-1ß in chondrocytes via the NADPH oxidase4-dependent and p38-MAPK mediated pathway, and accelerated cartilage degeneration in OA progression. These findings suggest an endogenous pathogenic role of AOPPs in OA progression. Targeting AOPPs-triggered cellular mechanisms might be a promising therapeutic option for patients with OA.
Subject(s)
Advanced Oxidation Protein Products/metabolism , Chondrocytes/cytology , Interleukin-1beta/metabolism , NADPH Oxidase 4/metabolism , Osteoarthritis, Knee/metabolism , Tumor Necrosis Factor-alpha/metabolism , Adult , Advanced Oxidation Protein Products/adverse effects , Aged , Animals , Cells, Cultured , Chondrocytes/metabolism , Disease Models, Animal , Disease Progression , Female , Humans , Male , Mice , Middle Aged , Osteoarthritis, Knee/chemically induced , Severity of Illness Index , Synovial Fluid/metabolism , Up-RegulationABSTRACT
Advanced oxidation protein products (AOPPs) can trigger NADPH oxidase (NOX) and lead to the production of reactive oxygen species (ROS) in the pathophysiology of rheumatoid arthritis (RA). Hydroxytyrosol (HT) is a phenolic composite in olive oil that has antioxidant and antiinflammatory effects and enhances autophagy. Early research has revealed that HT can activate the silent information regulator 1 (SIRT1) pathway to induce autophagy and alleviate the cartilage inflammatory response caused by H2O2. However, whether HT can attenuate AOPPinduced NOX and inflammatory responses remains to be elucidated. The present study aimed to investigate how HT can alleviate the damage caused by AOPPs. In cell experiments, chondrocytes were prestimulated with HT and then exposed to AOPPs. First, it was found that HT promoted autophagy through the SIRT1 pathway, increased the expression of autophagyrelated proteins including microtubuleassociated protein 1 light chain 3, autophagy related (ATG)5 and ATG7, and decreased the expression of P62. Furthermore, HT reduced the expression of NOX, which was affected by AOPPs in chondrocytes through the SIRT1 pathway. Finally, the expression of inflammatory cytokines caused by AOPPs was downregulated following HT treatment. In conclusion, it was found that HT reduced the expression of NOX and inhibited the inflammatory response caused by AOPPs in chondrocytes through the SIRT1 pathway.
Subject(s)
Advanced Oxidation Protein Products/pharmacology , Autophagy/drug effects , Inflammation/etiology , Inflammation/metabolism , NADPH Oxidases/metabolism , Phenylethyl Alcohol/analogs & derivatives , Sirtuin 1/genetics , Animals , Animals, Newborn , Cells, Cultured , Chondrocytes/drug effects , Chondrocytes/metabolism , Gene Expression Regulation , Inflammation/pathology , Interleukin-6/biosynthesis , Matrix Metalloproteinase 13/biosynthesis , Oxidation-Reduction/drug effects , Phenylethyl Alcohol/pharmacology , RNA Interference , Rats , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Sirtuin 1/metabolism , Tumor Necrosis Factor-alpha/biosynthesisABSTRACT
BACKGROUND: The purpose of this study was to compare the surgical outcomes of anterior decompression and fusion (ADF) with that of posterior laminoplasty (LAMP) for cervical myelopathy caused by ossification of posterior longitudinal ligament (OPLL). METHODS: We retrospectively assessed the medical records of patients who underwent surgery for cervical myelopathy owing to OPLL between 2007 and 2016 at our institution. Fifty patients were included in this study, including 17 patients in ADF group and 33 patients in LAMP group. Surgical outcomes were assessed under the Japanese Orthopaedic Association (JOA) score. The radiologic and clinical data were compared between two groups. RESULTS: There was no significant difference in age, follow-up time, operation time, blood loss, length of stay, preoperative JOA score, occupying ratio of OPLL, diameter of spinal canal, preoperative and final follow-up C2-C7 Cobb angles, and the change of C2-C7 Cobb angle before and after operation between ADF and LAMP groups. The final follow-up JOA score and the neurological recovery rate were significantly higher in ADF group than in LAMP group, particularly in patients with segmental-type OPLL. Cerebrospinal fluid leakage is a major complication after ADF, C5 paralysis, and axial pain frequently results from LAMP. CONCLUSION: Compared with LAMP, ADF shows better improvement of neurological function in patients with cervical myelopathy due to OPLL, especially in patients with segmental-type cervical OPLL.
Subject(s)
Cervical Vertebrae , Decompression, Surgical , Laminoplasty , Ossification of Posterior Longitudinal Ligament/complications , Spinal Cord Diseases/surgery , Spinal Fusion , Adult , Aged , Female , Humans , Male , Middle Aged , Operative Time , Ossification of Posterior Longitudinal Ligament/surgery , Retrospective Studies , Spinal Cord Diseases/etiology , Treatment OutcomeABSTRACT
OBJECTIVE: The postoperative change in cervical sagittal alignment has an impact on health-related quality of life in adolescent idiopathic scoliosis (AIS) patients who have undergone deformity correction. However, the effect of deformity correction on sagittal cervical profile is still controversial in the literatures. The objective of this study was to investigate the postoperative change in the cervical sagittal alignment of patients with AIS. PATIENTS AND METHODS: A total of 46 AIS patients treated by posterior instrumentation and fusion with pedicle screw constructs were included in the study. Radiographs were collected preoperatively, immediate postoperatively and at the final follow-up. The C2-C7 Cobb angle and C2-C7 sagittal vertical axis (cSVA) were used to assess the cervical sagittal alignment. Spinopelvic alignment parameters, such as thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), and sagittal vertical axis (SVA), were also measured. The correlations between the cervical sagittal parameters and spinopelvic parameters were analyzed. RESULTS: The incidence of cervical kyphosis was 67.4% preoperatively but increased to 87% postoperatively and 69.5% at the final follow-up. The C2-C7 Cobb angle significantly increased from pre-operation (-1.5°â¯±â¯15°) to post-operation (-5.4°â¯±â¯7.3°; Pâ¯<â¯0.05) and spontaneously decreased to -2.9°â¯±â¯10.5° at the final follow up. The cSVA was 18.1⯱â¯13â¯mm preoperatively, 17⯱â¯12.3â¯mm after surgery and 18.5⯱â¯9.5â¯mm at the last follow-up, but the change was not statistically significant (Pâ¯>â¯0.05). TK decreased significantly from pre-operation (17.7°â¯±â¯14.4°) to post-operation (14.2°â¯±â¯7.6°) and spontaneously improved to 16.9°â¯±â¯8.2° at the final follow-up. TK showed a significant correlation with the C2-C7 Cobb angle, but not with cSVA, in the preoperative (râ¯=â¯0.709, Pâ¯<â¯0.01), postoperative (râ¯=â¯0.472, Pâ¯<â¯0.01), and last follow-up measurements(râ¯=â¯0.505, Pâ¯<â¯0.01). Compared with patients with preoperative thoracic hypokyphosis or hyperkyphosis, patients with a normal thoracic spine had more significant postoperative changes in the C2-C7 Cobb angle and TK. CONCLUSIONS: Cervical sagittal alignment after deformity correction is altered in AIS patients. An increase in cervical kyphosis after surgery is correlated with a loss of thoracic kyphosis. The change in the cervical sagittal profile may be a compensatory mechanism in response to an abnormal thoracic sagittal profile.
Subject(s)
Cervical Vertebrae/surgery , Postoperative Period , Scoliosis/surgery , Thoracic Vertebrae/surgery , Adolescent , Child , Female , Humans , Kyphosis/surgery , Lordosis/surgery , Lumbar Vertebrae/surgery , Male , Posture/physiology , Spinal Fusion/methods , Young AdultABSTRACT
Osteoblast apoptosis contributes to age-related bone loss. Advanced oxidation protein products (AOPPs) are recognized as the markers of oxidative stress and potent inducers of apoptosis. We have demonstrated that AOPP accumulation was correlated with age-related bone loss. However, the effect of AOPPs on the osteoblast apoptosis still remains unknown. Exposure of osteoblastic MC3T3-E1 cells to AOPPs caused the excessive generation of reactive oxygen species (ROS) by activating nicotinamide adenine dinucleotide phosphate (NADPH) oxidases. Increased ROS induced phosphorylation of mitogen-activated protein kinases (MAPKs), which subsequently triggered intrinsic apoptosis pathway by inducing mitochondrial dysfunction, endoplasmic reticulum stress, and Ca2+ overload and eventually leads to apoptosis. Chronic AOPP loading in aged Sprague-Dawley rats induced osteoblast apoptosis and activated NADPH oxidase signaling cascade, in combination with accelerated bone loss and deteriorated bone microstructure. Our study suggests that AOPPs induce osteoblast apoptosis by the NADPH oxidase-dependent, MAPK-mediated intrinsic apoptosis pathway.
Subject(s)
Advanced Oxidation Protein Products/metabolism , Apoptosis , Mitogen-Activated Protein Kinases/metabolism , NADPH Oxidases/metabolism , Osteoblasts/metabolism , 3T3 Cells , Animals , Cells, Cultured , Male , Mice , Osteoblasts/pathology , Rats , Rats, Sprague-DawleyABSTRACT
INTRODUCTION: Patients with social anxiety disorder (SAD) have a cognitive preference to negatively evaluate emotional information. In particular, the preferential biases in prosodic emotion recognition in SAD have been much less explored. The present study aims to investigate whether SAD patients retain negative evaluation biases across visual and auditory modalities when given sufficient response time to recognise emotions. METHODS: Thirty-one SAD patients and 31 age- and gender-matched healthy participants completed a culturally suitable non-verbal emotion recognition task and received clinical assessments for social anxiety and depressive symptoms. A repeated measures analysis of variance was conducted to examine group differences in emotion recognition. RESULTS: Compared to healthy participants, SAD patients were significantly less accurate at recognising facial and prosodic emotions, and spent more time on emotion recognition. The differences were mainly driven by the lower accuracy and longer reaction times for recognising fearful emotions in SAD patients. Within the SAD patients, lower accuracy of sad face recognition was associated with higher severity of depressive and social anxiety symptoms, particularly with avoidance symptoms. CONCLUSION: These findings may represent a cross-modality pattern of avoidance in the later stage of identifying negative emotions in SAD. This pattern may be linked to clinical symptom severity.