Effect of Advanced Oxidation Protein Products (AOPPs) and aging on the osteoclast differentiation of Myeloid-Derived Suppressor Cells (MDSCs) and its preliminary mechanism.

To verify the osteoclast differentiation ability of MDSCs from mice of different ages and explore the effect of AOPPs on the osteoclast differentiation of bone marrow MDSCs. Bone marrow cells from C57BL/6 (a.k.a C57) mice of different ages were subjected to flow cytometry, and CD11b+Ly6C+Ly6G+ MDSCs were sorted out. After induction of osteoclast differentiation, these cells were subjected to tartrate-resistant acid phosphatase (TRAP) and F-actin. MDSCs from bone marrows of old mice were injected into the tibial medullary cavity of young mice. One week later, the bone marrows were subjected to histological examination, TRAP, and cell count. MDSCs from bone marrows of old mice were sorted for induction of osteoclast differentiation, intervened with reactive oxygen species (ROS) scavenger, inducible nitric oxide synthase (iNOS) inhibitor, and nitric oxide (NO) scavenger, and then subjected to TRAP. 8-weeks-old C57 mice were injected with the same concentrations of either AOPPs or mouse serum albumin (MSA). Four weeks later, MDSCs from bone marrows were sorted and subjected to induction of osteoclast differentiation, followed by IHC staining and TRAP. MDSCs of 8-weeks-old C57 mice were extracted and subjected to in vitro induction of osteoclast differentiation with different concentrations of AOPPs, followed by TRAP training. The number of MDSCs in the bone marrows of old mice was significantly higher than that in young mice. MDSCs from bone marrows of old mice differentiated into large multinucleated TRAP+ osteoclasts, which were significantly different from those in the middle-aged and young mice in terms of cell quantity and morphology. The actin rings formed in the differentiated osteoclasts from MDSCs of bone marrows were densely distributed in the whole field of view, which were significantly denser than those in the middle-aged and young mice. After injection of MDSCs of old mice, the number of TRAP + osteoclasts in the tibial medullary cavity of young mice was significantly increased. NO inhibitor can significantly inhibit the osteoclast differentiation capacity of MDSCs from bone marrows of old mice. In vivo treatment with AOPPs significantly increased the proportion of MDSCs in the bone marrow, which is up to 55.2%. After injection of AOPPs in 8-week-old mice and induction of osteoclast differentiation from the MDSCs, the ratios of CD11b+ and Gr1+ cells were significantly higher than that in the control and MSA groups but was not significantly different from that in the 15-month-old mice. Upon in vitro treatment with different concentrations of AOPPs, the MDSCs did not show any sign of osteoclast differentiation. MDSCs can directly undergo osteoclast differentiation, the capacity of which is stronger in MDSCs of bone marrows of old mice; the NO pathway is a potential mechanism underlying this phenomenon. In vivo but not in vitro AOPPs treatment can induce osteoclast differentiation of MDSCs, indicating there might be other factors in the body that can interact with AOPPs to induce osteoclast differentiation of MDSCs.

Proteomics and bioinformatics reveal insights into neuroinflammation in the acute to subacute phases in rat models of spinal cord contusion injury.

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.

MRI-based vertebral bone quality score effectively reflects bone quality in patients with osteoporotic vertebral compressive fractures.

OBJECTIVE: The present study is aimed to validate the ability of the vertebral bone quality (VBQ) score to evaluate bone quality in patients with osteoporotic vertebral compression fractures (OVCF) and to compare it with the ability of T-score by DXA. In addition, the sensitivity of VBQ score with cerebrospinal fluid (CSF) of L2 and L3 segments as baseline is evaluated. METHODS: 196 inpatients were collected and assigned into OVCF and Non-OVCF groups, respectively. For each patient, the VBQ score was calculated by the signal intensity of the L1-L4 vertebral bodies and CSF at L3 or L2 level from T1-weighted MRIs, while T-score from DXA was also obtained. The VBQ and T-score was compared between OVCF and non-OVCF groups, and among age groups. The OVCF ORs by VBQ score and T-score were calculated using logistic regression. RESULTS: OVCF group was significantly different to the non-OVCF group in the T-score (- 2.9 vs. - 0.7) and VBQ score (4.0 vs. 3.5). VBQ score and T-score in patient aged 60-79 years old could indicate the bone quality, but only T-score in patients aged 50-59 years old. OVCF are associated with both higher VBQ score and lower T-score. The VBQ scores calculated by L2 CSF and L3 CSF were similar. CONCLUSIONS: The VBQ score is an effective indicator of bone quality in OVCF patients and comparable to T-score, particularly in people over 60 years old. The VBQ score is not sensitive to CSF of different segments as a baseline.

Anatomical analysis of the C2 pedicle in patients with basilar invagination.

PURPOSE: To evaluate and describe the morphologic features of the C2 pedicle in patients with basilar invagination (BI) for informing the placement of pedicle screws. C2 pedicle screw placement is an important surgical technique for the treatment of atlantoaxial instability in patients with BI. However, no systematic and comprehensive anatomical study of the C2 pedicle in patients with BI has been reported. METHODS: The data from 100 patients diagnosed with BI (BI group) and 100 patients without head or cervical disease (control group) were included in the study. Radiographic parameters, including the pedicle width, length, height, transverse angle, lamina angle, and superior angle, were measured and analyzed on CT images. After summary analysis, the effect of C2-3 congenital fusion on C2 pedicle deformity in patients with BI was also investigated. RESULTS: The width, length, and height of the C2 pedicle of the BI patients were smaller than those of the control group. The pedicle cancellous bone was smaller in the BI group, while no significant difference in cortical bone was observed. In total, 44% of the pedicles were smaller than 4.5 mm in the BI group. Patients with C2-3 congenital fusion presented with smaller pedicle transverse angles and larger pedicle superior angles than those without fusion. Wide variations in the left and right angles of the pedicle were observed in the BI group with atlantoaxial dislocation or atlantooccipital fusion. CONCLUSION: The C2 pedicle in the BI group was thinner than that in the control group due to a smaller cortical bone. Cases of C2-3 congenital fusion, atlantoaxial dislocation, and atlantooccipital fusion displayed variation in the angle of the C2 pedicle.

Insulin sensitizer and antihyperlipidemic effects of Cajanus cajan (L.) millsp. root in methylglyoxal-induced diabetic rats.

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.

NPS-1034 Induce Cell Death with Suppression of TNFR1/NF-κB Signaling in Testicular Cancer.

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.

Posterior unilateral exposure and stability reconstruction with pedicle and lamina screw fixation for the cervical dumbbell tumorectomy: a case report and biomechanical study.

PURPOSE: Cervical dumbbell tumor is usually removed via a posterior approach and may require the spinal fixation sometimes. However, the present surgical methods involved either more trauma or a higher risk of instability of the cervical spine. A new technique of unilateral exposure and stability reconstruction with pedicle and lamina screws fixation for posterior cervical dumbbell tumorectomy was described and compared with conventional techniques. METHODS: Posterior unilateral exposure, hemi-laminectomy and facetectomy were performed in one patient with the cervical dumbbell tumor between C3 and C4. The stability was reconstructed by the unilateral pedicle and lamina screws fixation (UPLS), and a strip of shaped allograft bone was also implanted between the superior and inferior lateral mass. Biomechanical stability test of this new technique was investigated using seven fresh-frozen human cervical spine specimens (C4-C7) and compared with unilateral pedicle screw (UPS) and bilateral pedicle screw fixation (BPS) techniques. A continuous pure moment of ± 2.0 Nm was applied to the specimen in flexion, extension, lateral bending and axial rotation. RESULTS: The cervical dumbbell tumor was removed completely, and bone fusion with continuous bone trabecula was maintained in the patient on the final follow-up examination at 18 months postoperatively. Biomechanical stability tests revealed that the range of motion of the UPLS fixation plus graft bone implant was the same as the BPS fixation in flexion (1.8°vs. 1.5°, p = 0.58) and extension (2.3°vs. 2.2°, p = 0.73), but significantly bigger in lateral bending (3.9° vs. 1.0°, p < 0.001) and axial rotation (6.8° vs. 3.8°, p = 0.002), which were significantly smaller than the UPS fixation in all directions (all p < 0.001). CONCLUSIONS: For the treatment of cervical dumbbell tumor, posterior unilateral exposure and stability reconstruction with pedicle and lamina screws fixation following hemi-laminectomy and facetectomy appear to be a more stable and lesser trauma technique. LEVEL OF EVIDENCE: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

Advanced oxidation protein products induce microglia-mediated neuroinflammation via MAPKs-NF-κB signaling pathway and pyroptosis after secondary spinal cord injury.

BACKGROUND: Inflammatory response mediated by oxidative stress is considered as an important pathogenesis of spinal cord injury (SCI). Advanced oxidation protein products (AOPPs) are novel markers of oxidative stress and their role in inflammatory response after SCI remained unclear. This study aimed to investigate the role of AOPPs in SCI pathogenesis and explore the possible underlying mechanisms. METHODS: A C5 hemi-contusion injury was induced in Sprague-Dawley rats to confirm the involvement of AOPPs after SCI. For in vivo study, apocynin, the NADPH oxidase inhibitor was used to study the neuroprotective effects after SCI. For in vitro study, the BV2 microglia cell lines were pretreated with or without the inhibitor or transfected with or without small interference RNA (siRNA) and then stimulated with AOPPs. A combination of molecular and histological methods was used to clarify the mechanism and explore the signaling pathway both in vivo and in vitro. One-way analysis of variance (ANOVA) was conducted with Bonferroni post hoc tests to examine the differences between groups. RESULTS: The levels of AOPPs in plasma and cerebrospinal fluid as well as the contents in the spinal cord showed significant increase after SCI. Meanwhile, apocynin ameliorated tissue damage in the spinal cord after SCI, improving the functional recovery. Immunofluorescence staining and western blot analysis showed activation of microglia after SCI, which was in turn inhibited by apocynin. Pretreated BV2 cells with AOPPs triggered excessive generation of reactive oxygen species (ROS) by activating NADPH oxidase. Increased ROS induced p38 MAPK and JNK phosphorylation, subsequently triggering nuclear translocation of NF-κB p65 to express pro-inflammatory cytokines. Also, treatment of BV2 cells with AOPPs induced NLRP3 inflammasome activation and cleavage of Gasdermin-d (GSDMD), causing pyroptosis. This was confirmed by cleavage of caspase-1, production of downstream mature interleukin (IL)-1ß and IL-18 as well as rupture of rapid cell membrane. CONCLUSIONS: Collectively, these data indicated AOPPs as biomarkers of oxidative stress, modulating inflammatory response in SCI by multiple signaling pathways, which also included the induction of NADPH oxidase dependent ROS, and NLRP3-mediated pyroptosis, and activation of MAPKs and NF-κB.

Inhalable Nanocomposite Microparticles with Enhanced Dissolution and Superior Aerosol Performance.

Previous studies have shown that combining colistin (Col), a cationic polypeptide antibiotic, with ivacaftor (Iva), a cystic fibrosis (CF) drug, could achieve synergistic antibacterial effects against Pseudomonas aeruginosa. The purpose of this study was to develop dry powder inhaler formulations for co-delivery of Col and Iva, aiming to treat CF and lung infection simultaneously. In order to improve solubility and dissolution for the water-insoluble Iva, Iva was encapsulated into bovine serum albumin (BSA) nanoparticles (Iva-BSA-NPs). Inhalable composite microparticles of Iva-BSA-NPs were produced by spray-freeze-drying using water-soluble Col as the matrix material and l-leucine as an aerosol enhancer. The optimal formulation showed an irregularly shaped morphology with fine particle fraction (FPF) values of 73.8 ± 5.2% for Col and 80.9 ± 4.1% for Iva. Correlations between "D×ρtapped" and FPF were established for both Iva and Col. The amorphous solubility of Iva is 66 times higher than the crystalline solubility in the buffer. Iva-BSA-NPs were amorphous and remained in the amorphous state after spray-freeze-drying, as examined by powder X-ray diffraction. In vitro dissolution profiles of the selected DPI formulation indicated that Col and Iva were almost completely released within 3 h, which was substantially faster regarding Iva release than the jet-milled physical mixture of the two drugs. In summary, this study developed a novel inhalable nanocomposite microparticle using a synergistic water-soluble drug as the matrix material, which achieved reduced use of excipients for high-dose medications, improved dissolution rate for the water-insoluble drug, and superior aerosol performance.

Serum cystatin C is increased in acute spinal cord injury: a multicentre retrospective study.

STUDY DESIGN: A multicentre retrospective study. OBJECTIVE: A multicentre retrospective study was performed to observe the changes in serum cystatin C (CysC) levels in patients with acute spinal cord injury (SCI). SETTING: Four hospitals in China. METHODS: Over a 5-year study period, the CysC, creatinine (Cr), and blood urea nitrogen (BUN) levels of people who had incurred SCI in the preceding 7 days were collected and compared with those of people with limb fracture (LF) who were matched for injury time and gender. People with SCI also were grouped by injury duration, ASIA Impairment Scale (AIS) grade and the presence or absence of steroid therapy and compared each day. RESULTS: Three hundred and twenty-three samples from people with SCI were retrospectively collected; their mean serum CysC levels were significantly higher than those of people with LF (p < 0.001); No significant difference was observed in Cr or BUN levels between the two groups (p > 0.14). CysC levels increased on the second day, peaked on day 3, and returned to normal on day 5. The more severely injured individuals had higher CysC levels. Steroid therapy or not had no influence for CysC levels. CONCLUSION: CysC levels are increased in patients with acute SCI, possibly as a direct result of injury. Serum CysC is a potential biomarker of SCI.

Straighter low lumbar curvature in isthmic spondylolisthesis at L4.

BACKGROUND: This study was conducted to compare differences in imaging features and clinical symptoms between patients with single-level isthmic spondylolisthesis (IS) at L4 and at L5 and to investigate the correlation between imaging and clinical parameters. METHODS: This cross-sectional study evaluated patients with single-level IS who were enrolled between June 2011 and June 2018. A total of 139 patients, 44 in the L4 IS group and 95 in the L5 IS group, met the study criteria and were included. Imaging and clinical parameters obtained from the two groups were compared and analyzed. RESULTS: Patients in the L4 IS group had smaller lower lumbar lordosis (LLL) (27.1 ± 8.2 vs. 30.9 ± 9.3, P = 0.021) and were of older age (58.5 ± 8.7 vs. 52.8 ± 10.1, P < 0.01) than those in the L5 IS group. As per the Roussouly classification system, most patients with L4 IS were classified as Type 2 (43.2%), whereas most patients with L5 IS fell under Type 3 (44.2%). In the L5 IS group, pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), and L5 incidence (L5I) were positively associated with slippage rate (SR), but the lumbosacral angle (LSA) was negatively associated with SR (P < 0.01). In the L4 IS group, only L5I showed a positive association with SR (P < 0.01). More significant associations were found among sagittal lumbo-pelvic parameters in the L5 IS group, but none were found between SR and Oswestry Disability Index (ODI) in either group. CONCLUSIONS: When compared with patients with L5 IS, patients with L4 IS were of older age and had straighter low lumbar curvature when they were obviously symptomatic. PI was an important parameter for patients with L5 IS while for those with L4 IS, L5I deserved more attention for its significantly positive correlation with the degree of slippage.

Usefulness of inflammatory markers and clinical manifestation for an earlier method to diagnosis surgical site infection after spinal surgery.

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.

The Effect of Sulforaphane on the Activity and Mineralization of Osteoblasts under Oxidative Stress.

Sulforaphane (SFN) is considered an antioxidant agent, but the biological effects on hypoxia-treated osteoblasts remain unclear. Therefore, the aims of this study were to investigate the effects of SFN on the activity and mineralization of osteoblasts in hypoxia. Osteoblasts were treated with hypoxia with or without SFN, and apoptosis was assayed with caspase 3 Activity Assay Kit and flow cytometer. The levels of reactive oxygen species (ROS) were measured with DCFH-DA. The levels of glutathione (GSH) and glutathione disulphide were determined by the o-phthalaldehyde fluorimetric assay. Mineralization of Osteoblasts was detected by Alizarin red staining and alkaline phosphatase (ALP) staining, and the relative proteins levels were examined by Western blotting. Our results showed that SFN reduced the hypoxia-mediated apoptosis and ROS levels in osteoblasts. The utilization of SFN improved the inhibitory effect of osteoblast mineralization by hypoxia. Additionally, the effect of alleviating hypoxia by SFN will be an increase in osteoblast activity. These findings clarify the effects of SFN on hypoxia-treated osteogenesis and will help identify novel therapeutic strategies for the protection of skeletal health.

Phospholipase C signaling activated by parathyroid hormone mediates the rapid osteoclastogenesis in the fracture healing of orchiectomized mice.

BACKGROUND: The age-related osteoporosis is an increasing risk severely threatening the live quality of aged people. Human parathyroid hormone (hPTH) is applied to the therapy of osteoporosis successfully, however, the mechanism, especially the signaling pathway activated in the healing fracture by PTH is still unknown. METHODS: The once daily injections of hPTH(1-34) and GR (1-34) (the PLC deficient analog) into the orchiectomized male mice with bone fracture, were started at the second day after fracture and lasted for 4 weeks. To explore the role of phospholipase C signaling in the androgen-deficient fracture healing, the fracture healing were evaluated via radiography, micro-CT, biomechanics testing, serum biochemistry, bone marrow cell culture and gene expression quantification. RESULTS: After two weeks of fracture, both peptides significantly increased bone mineral density (BMD), bone mass content (BMC) and bone volume (BV/TV) in the healing area. However, compared to hPTH(1-34), GR(1-34) induced more woven bones, the higher BMC and BMD, as well as the less serum TRAP and osteoclasts. After four weeks of treatment, the effects of hPTH(1-34) on fracture healing showed no difference to those of GR(1-34). Consistently, GR(1-34) induced the similar osteogenesis but less osteoclastogenesis under the ex vivo condition immediately after administration compared to hPTH(1-34), which was verified by the weaker activation of RANKL, NFATC1, TRAP and Cathepsin K in GR(1-34) treatment. CONCLUSION: These results indicated that the PLC signaling activated by the intermittent injection of hPTH(1-34) leads to the bone resorption by rapidly activating the osteoclastogenesis in the fracture healing zone.

Advanced oxidation protein products induce chondrocyte death through a redox-dependent, poly (ADP-ribose) polymerase-1-mediated pathway.

This study aimed to investigate the effect of AOPPs on apoptosis in human chondrocytes. Chondrocytes were treated with AOPPs. Cell death, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, reactive oxygen species (ROS) generation, and the expression of apoptotic proteins were detected in vitro. AOPPs levels were detected by colorimetric method. The results in vitro demonstrated that AOPPs induced cell death in human chondrocyte through a redox-dependent pathway, including RAGE-mediated, NADPH oxidase-dependent ROS generation, and poly (ADP-ribose) polymerase-1 (PARP-1) activation. Targeting AOPPs-induced cellular mechanisms might emerge as a promising therapeutic option for patients with RA.

Facial and prosodic emotion recognition in social anxiety disorder.

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.

Advanced oxidation protein products induce chondrocyte apoptosis via receptor for advanced glycation end products-mediated, redox-dependent intrinsic apoptosis pathway.

Pro-inflammatory cytokine-induced chondrocyte apoptosis is a primary cause of cartilage destruction in the progression of rheumatoid arthritis (RA). Advanced oxidation protein products (AOPPs), a novel pro-inflammatory mediator, have been confirmed to accumulate in patients with RA. However, the effect of AOPPs accumulation on chondrocyte apoptosis and the associated cellular mechanisms remains unclear. The present study demonstrated that the plasma formation of AOPPs was enhanced in RA rats compared with normal. Then, chondrocyte were treated with AOPPs-modified rat serum albumin (AOPPs-RSA) in vitro. Exposure of chondrocyte to AOPPs activated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and increased expression of NADPH oxidase subunits, which was mediated by receptor for advanced glycation end products (RAGE), but not scavenger receptor CD36. Moreover, AOPPs challenge triggered NADPH oxidase-dependent ROS generation which induced mitochondrial dysfunction and endoplasmic reticulum stress resulted in activation of caspase family that eventually lead to apoptosis. Lastly, blockade of RAGE, instead of CD36, largely attenuated these signals. Our study demonstrated first time that AOPPs induce chondrocyte apoptosis via RAGE-mediated and redox-dependent intrinsic apoptosis pathway in vitro. These data implicates that AOPPs may represent a novel pathogenic factor that contributes to RA progression. Targeting AOPPs-triggered cellular mechanisms might emerge as a promising therapeutic option for patients with RA.

Oligogalacturonic acids promote tomato fruit ripening through the regulation of 1-aminocyclopropane-1-carboxylic acid synthesis at the transcriptional and post-translational levels.

BACKGROUND: Oligogalacturonic acids (OGs) are oligomers of alpha-1,4-linked galacturonosyl residues that are released from cell walls by the hydrolysis of polygalacturonic acids upon fruit ripening and under abiotic/biotic stress. OGs may induce ethylene production and fruit ripening, however, the mechanism(s) behind these processes is unknown. RESULTS: Tomato cultivar 'Ailsa Craig' (AC) and mutant Neverripe, ripening inhibitor, non-ripening, and colorless non-ripening fruits were treated with OGs at different stages. Only AC fruits at mature green stage 1 showed an advanced ripening phenomenon, although transient ethylene production was detected in all of the tomato fruits. Ethylene synthesis genes LeACS2 and LeACO1 were rapidly up-regulated, and the phosphorylated LeACS2 protein was detected after OGs treatment. Protein kinase/phosphatase inhibitors significantly affected the ripening process induced by the OGs. As a potential receptor of OGs, LeWAKL2 was also up-regulated in their presence. CONCLUSIONS: We demonstrated that OGs promoted tomato fruit ripening by inducing ethylene synthesis through the regulation of LeACS2 at transcriptional and post-translational levels.

Is duration of preoperative anti-tuberculosis treatment a risk factor for postoperative relapse or non-healing of spinal tuberculosis?

PURPOSE: This study evaluated the relationship between spinal TB postoperative recurrence or non-healing and duration of preoperative anti-TB treatment (ATT). METHODS: From January 2004 to January 2013, patients who underwent surgery for spinal TB and met this study's inclusion criteria were retrospectively reviewed. Observed parameters were age, sex, initial ESR, preoperative ESR, degree of ESR change, initial CRP, preoperative CRP, degree of CRP change, duration of preoperative ATT, surgical approach, presence of internal fixation, location of spinal lesion, number of involved segments, duration of operation, and intraoperative blood loss. The data were analyzed by univariate and multivariate analyses for spinal TB recurrence or non-healing to determine related risk factors. RESULTS: A total of 223 patients met the inclusion criteria. There were 84 female and 139 male patients with a mean age of 42.2 years (range 2-85 years). The follow-up period was 18-72 months (average 28.7 months). Among 223 patients observed, 23 patients had postoperative relapse or non-healing (10.3 %) during the follow-up period. Statistical analysis indicated that the location of a spinal lesion was significantly associated with postoperative relapse or non-healing. Risk of postoperative relapse or non-healing in thoracolumbar TB was 2.524-fold (95 % CI 1.026-6.580) that of lumbosacral TB. CONCLUSIONS: Duration of preoperative ATT may not be a risk factor for postoperative recurrence or non-healing of spinal TB. Junctional zones such as the lumbosacral and thoracolumbar junction have a higher recurrence rate than non junctional.

Reoperation After Cervical Disc Arthroplasty Versus Anterior Cervical Discectomy and Fusion: A Meta-analysis.

BACKGROUND: Anterior cervical discectomy and fusion is a standard surgical treatment for cervical radiculopathy and myelopathy, but reoperations sometimes are performed to treat complications of fusion such as pseudarthrosis and adjacent-segment degeneration. A cervical disc arthroplasty is designed to preserve motion and avoid the shortcomings of fusion. Available evidence suggests that a cervical disc arthroplasty can provide pain relief and functional improvements similar or superior to an anterior cervical discectomy and fusion. However, there is controversy regarding whether a cervical disc arthroplasty can reduce the frequency of reoperations. QUESTIONS/PURPOSES: We performed a meta-analysis of randomized controlled trials (RCTs) to compare cervical disc arthroplasty with anterior cervical discectomy and fusion regarding (1) the overall frequency of reoperation at the index and adjacent levels; (2) the frequency of reoperation at the index level; and (3) the frequency of reoperation at the adjacent levels. METHODS: PubMed, EMBASE, and the Cochrane Register of Controlled Trials databases were searched to identify RCTs comparing cervical disc arthroplasty with anterior cervical discectomy and fusion and reporting the frequency of reoperation. We also manually searched the reference lists of articles and reviews for possible relevant studies. Twelve RCTs with a total of 3234 randomized patients were included. Eight types of disc prostheses were used in the included studies. In the anterior cervical discectomy and fusion group, autograft was used in one study and allograft in 11 studies. Nine of 12 studies were industry sponsored. Pooled risk ratio (RR) and associated 95% CI were calculated for the frequency of reoperation using random-effects or fixed-effects models depending on the heterogeneity of the included studies. A funnel plot suggested the possible presence of publication bias in the available pool of studies; that is, the shape of the plot suggests that smaller negative or no-difference studies may have been performed but have not been published, and so were not identified and included in this meta-analysis. RESULTS: The overall frequency of reoperation at the index and adjacent levels was lower in the cervical disc arthroplasty group (6%; 108/1762) than in the anterior cervical discectomy and fusion group (12%; 171/1472) (RR, 0.54; 95% CI, 0.36-0.80; p = 0.002). Subgroup analyses were performed according to secondary surgical level. Compared with anterior cervical discectomy and fusion, cervical disc arthroplasty was associated with fewer reoperations at the index level (RR, 0.50; 95% CI, 0.37-0.68; p < 0.001) and adjacent levels (RR, 0.52; 95% CI, 0.37-0.74; p < 0.001). CONCLUSIONS: Cervical disc arthroplasty is associated with fewer reoperations than anterior cervical discectomy and fusion, indicating that it is a safe and effective alternative to fusion for cervical radiculopathy and myelopathy. However, because of some limitations, these findings should be interpreted with caution. Additional studies are needed. LEVEL OF EVIDENCE: Level I, therapeutic study.