Mammalian STE20-like kinase 1 inhibits synoviocytes activation in rheumatoid arthritis through mitochondrial dysfunction mediated by SIRT3/mTOR axis.

BACKGROUND: Mammalian STE20-like kinase 1 (MST1) is involved in the occurrence of cancer and autoimmune diseases by regulating cell proliferation, differentiation, apoptosis and other functions. However, its role and downstream targets in rheumatoid arthritis (RA) remain unclear. METHODS: The model of RA fibroblast-like synoviocytes (RA-FLSs) overexpressing MST1 was constructed by lentiviral transfection in vitro and analyzed the effects of MST1 on apoptosis, migration, invasion, and inflammation of RA-FLSs. The effect of MST1 on joint synovial membrane inflammation and bone destruction was observed in vivo by establishing a rat model of arthritis with complete Freund's adjuvant. RESULTS: MST1 is down-regulated in RA-FLSs, and up-regulation of MST1 inhibits the survival, migration, invasion and inflammation of RA-FLSs. Mechanistically, MST1 inhibits SIRT3/mTOR-signaling pathway, inducing decreased mitochondrial autophagy and increased mitochondrial fission, resulting in mitochondrial morphological abnormalities and dysfunction, and ultimately increased apoptosis. We have observed that activation of MST1 alleviates synovial inflammation and bone erosion in vivo. CONCLUSIONS: MST1 reduces the survival, migration, invasion and inflammation of FLSs by inhibiting the SIRT3/mTOR axis to reduce mitochondrial autophagy and promote mitochondrial division, thereby achieving the potential role of relieving rheumatoid arthritis.

Neutrophil Extracellular Traps Induce Pyroptosis of Rheumatoid Arthritis Fibroblast-Like Synoviocytes via the NF-κB/Caspase 3/GSDME Pathway.

Rheumatoid arthritis (RA) is an enduring, progressive autoimmune disorder. Abnormal activation of fibroblast-like synoviocytes (FLSs) has been proposed as the initiating factor for inflammation of the synovium and bone destruction. Neutrophil extracellular traps (NETs), which are web-like structures composed of DNA, histones, and granule proteins, are involved in the development of RA in multiple aspects. Pyroptosis, gasdermin-mediated inflammatory programmed cell death, plays a vital function in the etiopathogenesis of RA. However, the exact mechanism underlying NETs-induced pyroptosis in FLSs of RA and its impact on cellular pathogenic behavior remain undefined. In this study, we demonstrated that gasdermin E (GSDME) expression was upregulated in RA plasma and synoviums, which was positively correlated with the elevated cell-free DNA (cfDNA) and citrullinated histone 3 (Cit H3) levels in the plasma. Additionally, in vitro experiments have shown that NETs triggered caspase 3/GSDME-mediated pyroptosis in RA-FLSs, characterized by decreased cell viability, cell membrane blebbing, and rupture, as well as increased levels of pyroptosis-related proteins and pro-inflammatory cytokines. Again, silencing GSDME significantly inhibited pyroptosis and suppressed the migration, invasion, and secretion of pro-inflammatory cytokines in RA-FLSs. Furthermore, we also found that the nuclear factor-kappa B (NF-κB) pathway, serving as an upstream mechanism, was involved in FLS pyroptosis. In conclusion, our investigation indicated that NETs could induce RA-FLS pyroptosis and facilitate phenotypic transformation through targeting the NF-κB/caspase 3/GSDME axis. This is the first to explore the crucial role of NETs-induced FLS pyroptosis in the progression of RA, providing novel targets for the clinical management of refractory RA.

Preoperative systemic immune-inflammation index as a prognostic indicator for patients with urothelial carcinoma.

Background: The systemic immune-inflammation index (SII) is a cost-efficient indicator for carcinoma prognosis. However, its utility in urothelial carcinoma (UC) prognosis is disputed. This meta-analysis aims to assess SII's prognostic value in UC. Methods: A thorough search of databases including PubMed, Web of Science, Embase, Cochrane Library, and Scopus, was conducted to find studies until January 11, 2023. Eligibility criteria were applied to select studies. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted from selected studies and compiled in a meta-analysis to gauge SII's association with survival outcomes such as overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and progression-free survival (PFS). Results: This analysis includes 19 studies with 12505 UC patients. It was found that high SII significantly correlated with worse OS in UC patients (HR 1.430, 95% CI 1.237-1.653, P<0.001). High SII values also linked with poorer CSS (HR 1.913, 95% CI 1.473-2.485, P<0.001), RFS (HR 1.240, 95% CI 1.097-1.403, P=0.001), and PFS (HR 1.844, 95% CI 1.488-2.284, P<0.001) compared to low SII values. Subgroup analysis revealed SII's consistent prognostic value in UC across races, carcinoma types, sample sizes, and SII cut-off values, suggesting its potential as a prognostic indicator in UC patients. Conclusion: Current evidence suggests SII as a promising, cost-efficient predictor in UC patients. This meta-analysis indicates SII's potential as a valuable prognostic tool in UC patients. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=307643, identifier CRD42022307643.

Association of microRNA-146a rs57095329 Polymorphism with Susceptibility to Primary Gout in a Chinese Han Population.

BACKGROUND: MicroRNA-146a (miR-146a) plays a critical role in the regulation of autoinflammatory diseases, including gout. There is growing evidence that miR-146a gene single nucleotide polymorphisms (SNPs) are associated with different diseases, but no genetic relevance studies of miR-146a gene polymorphisms to gout have been reported by now. OBJECTIVE: The purpose of this study was to examine the relationship between the miR-146a rs57095329 genetic polymorphism and the susceptibility to primary gout in the Chinese Han population. METHODS: A case-control study was performed in this report to examine the potential association between gout and the functional rs57095329 SNP of miR-146a in a Chinese population consisting of 448 primary gout patients (containing 76 tophi patients) and 418 healthy controls. MiR-146a expression in peripheral blood mononuclear cells (PBMCs) was measured in 81 gout patients (including 32 tophi patients and 49 non-tophi patients) and 47 healthy subjects. RESULTS: There was no significant difference found in the distribution of miR-146a rs57095329 between 448 gout patients and 418 healthy subjects (P > 0.05). However, significant differences in genotypes and allele distributions were found between 76 gout with tophi patients and 418 healthy subjects, as well as between gout with tophi (76) and with no tophi patients (372) (P < 0.01, respectively). Gout patients with AG/GG genotypes had a 0.323-fold reduced risk for tophi than those with the AA genotype, and the G allele had a 0.362-fold reduced risk of tophi. Furthermore, in 32 tophi patients, the GG genotype was significantly associated with increased expression of miR- 146a. CONCLUSION: Our findings suggest that rs57095329 may play a protective role in tophi gout susceptibility, and rs57095329 A > G variant may modulate the expression of miR-146a in tophi patients.

Biomechanical investigation of S2 alar-iliac screw and S1 pedicle screw fixation in the treatment of Denis type II sacral fractures.

Although S2 alar-iliac screw technique has been widely used in spinal surgery, its applicability to pelvic fractures is largely unknown. This study aimed to evaluate the biomechanical stability of S2 alar-iliac screw and S1 pedicle screw fixation in the treatment of Denis II sacral fractures. Twenty-eight artificial pelvic fracture models were treated with unilateral lumbopelvic fixation, sacroiliac screw fixation, S2 alar-iliac screw and S1 pedicle screw fixation, and S2 alar-iliac screw and contralateral S1 pedicle screw fixation (Groups 1-4, respectively; N = 7 per group). Each model was cyclically tested under increasing axial compression. Optical motion-tracking was used to assess relative displacement and gap angle, and the number of failure cycles. Relative displacement was significantly smaller in Group 3 than in Groups 1 (p = 0.004) and 4 (p < 0.001) but not significantly different between Groups 3 and 2 (p = 0.290). The gap angle in Group 3 was significantly smaller than that in Group 1 (p = 0.009) on the sagittal plane but significantly larger than that in Group 4 (p = 0.006) on the horizontal plane. A number of failure cycles was significantly higher in Group 3 than in Groups 1 (p = 0.002) and 4 (p = 0.004) but not significantly different between Groups 3 and 2 (p = 0.910). From a biomechanical perspective, S2 alar-iliac screw and S1 pedicle screw fixation can provide good stability in the treatment of Denis II sacral fractures.

Biomechanical comparison of the undercut thread design versus conventional buttress thread for the lag screw of the dynamic hip screw system.

Objective: To compare the fixation stability of the lag screw with a undercut thread design for the dynamic hip screw (DHS) system versus the lag screw with the conventional buttress thread. Methods: The lag screws with the undercut thread (a flat crest feature, a tip-facing undercut feature) and buttress thread were both manufactured. Fixation stability was investigated using cyclic compressive biomechanical testing on custom osteoporotic femoral head sawbone. The forces required for the same vertical displacement in the two types of lag screw were collected to evaluate the resistance to migration. Varus angle was measured on X-ray images to assess the ability in preventing varus collapse. Finite element analysis (FEA) was performed to analyze the stress and strain distribution at the bone-screw interface of the two types of lag screws. Results: The biomechanical test demonstrated that the force required to achieve the same vertical displacement of the lag screw with the undercut thread was significantly larger than the lag screw with conventional buttress thread (p < 0.05). The average varus angles generated by the undercut and buttress threads were 3.38 ± 0.51° and 5.76 ± 0.38°, respectively (p < 0.05). The FEA revealed that the region of high-stress concentration in the bone surrounding the undercut thread was smaller than that surrounding the buttress thread. Conclusion: The proposed DHS system lag screw with the undercut thread had higher migration resistance and superior fixation stability than the lag screw with the conventional buttress thread.

Treatment of Unstable Posterior Pelvic Ring Injury with S2-Alar-Iliac Screw and S1 Pedicle Screw Fixation.

OBJECTIVE: The S2-alar-iliac (S2AI) screws have been described as an alternative method for lumbosacropelvic fixation in place of iliac screws. However, the clinical effect of the short-segment S2AI screw fixation technique in the treatment of unstable posterior pelvic ring injuries remains unclear. In this study, we report the preliminary clinical results of the internal fixation connecting a S2-alar-iliac screw and a S1 pedicle screw (i.e., S2AI-S1 fixation) in the treatment of unstable pelvic posterior ring injuries. METHODS: Twenty-five patients with unstable posterior pelvic ring injury were treated with S2AI-S1 fixation from February 2019 to June 2020. The incision length, surgical time, blood loss, frequency of intraoperative fluoroscopy, quality of reduction, complications, and functional outcome were analyzed. RESULTS: A total of 29 groups of S2AI-S1 fixation were used in 25 patients. The mean incision length was 8.3 (6.2 - 10.3) cm, mean operative time was 86.4 (60 - 142) minutes, mean frequency of intraoperative fluoroscopy was 7.9 (4 - 12) times, and mean blood loss was 148 (50 - 500) mL. The mean postoperative follow-up time was 17.8 (10 - 26) months. The satisfaction rate of pelvic reduction quality was 25/29, and the satisfactory rate of functional outcome was 23/25. There were no obvious signs of screw prominence, screw loosening, or implant failure. CONCLUSIONS: The case series presented in this study show the successful use of S2AI-S1 fixation to treat unstable posterior pelvic ring injuries. The S2AI-S1 fixation, not including the lumbar spine in the fixation range, is a simple, safe, and effective fixation method.

Applicable safety analysis and biomechanical study of iliosacral triangular osteosynthesis.

BACKGROUND: The aim of this study was to investigate the applicable safety and biomechanical stability of iliosacral triangular osteosynthesis (ITO) through 3D modeling and finite element (FE) analysis. METHODS: Pelvic CT imaging data from 100 cases were imported into Mimics software for the construction of 3D pelvic models. The S2-alar-iliac (S2AI) screws and S2 sacroiliac screws were placed in the S2 segment with optimal distribution and their compatibility rate on the S2 safe channel was observed and analyzed. In the FE model, the posterior pelvic ring was fixed with two transsacral screws (TTS), triangular osteosynthesis (TO) and ITO, respectively. Four different loading methods were implemented in sequence to simulate the force in standing, flexion, right bending, and left twisting, respectively. The relative displacement and change in relative displacement of the three fixing methods were recorded and analyzed. RESULTS: The theoretical compatibility rate of S2AI screw and S2 sacroiliac screw in S2 segment was 94%, of which 100% were in males and 88% in females. In the FE model, in terms of overall relative displacement, TTS group showed the smallest relative displacement, the ITO group showed the second smallest, and the TO group the largest relative displacement. The change in relative displacement of the TTS group displayed the smaller fluctuations in motion. The change in relative displacement of the TO group under right bending and left twisting displayed larger fluctuations, while the ITO group under flexion displayed larger fluctuations. CONCLUSIONS: The simultaneous placement of S2AI screw and S2 sacroiliac screw in the S2 segment is theoretically safe. Although the biomechanical stability of ITO is slightly lower than TTS, it is better than TO, and can be used as a new method for the treatment of posterior pelvic ring injuries.

S2-alar-iliac screw and S1 pedicle screw fixation for the treatment of non-osteoporotic sacral fractures: a finite element study.

BACKGROUND: Five different sacral fracture fixation methods were compared using finite element (FE) analysis to study their biomechanical characteristics. METHODS: Denis type I sacral fractures were created by FE modeling. Five different fixation methods for the posterior pelvic ring were simulated: sacroiliac screw (SIS), lumbopelvic fixation (LPF), transiliac internal fixator (TIFI), S2-alar-iliac (S2AI) screw and S1 pedicle screw fixation (S2AI-S1) and S2AI screw and contralateral S1 pedicle screw fixation (S2AI-CS1). Four different loading methods were implemented in sequence to simulate the force in standing, flexion, right bending and left twisting, respectively. Vertical stiffness, relative displacement and change in relative displacement were recorded and analyzed. RESULTS: As predicted by the FE model, the vertical stiffness of the five groups in descending order was S2AI-S1, SIS, S2AI-CS1, LPF and TIFI. In terms of relative displacement, groups S2AI-S1 and S2AI-CS1 displayed a lower mean relative displacement, although group S2AI-CS1 exhibited greater displacement in the upper sacrum than group S2AI-S1. Group SIS displayed a moderate mean relative displacement, although the displacement of the upper sacrum was smaller than the corresponding displacement in group S2AI-CS1, while groups LPF and TIFI displayed larger mean relative displacements. Finally, in terms of change in relative displacement, groups TIFI and LPF displayed the greatest fluctuations in their motion, while groups SIS, S2AI-S1 and S2AI-CS1 displayed smaller fluctuations. CONCLUSION: Compared with SIS, unilateral LPF and TIFI, group S2AI-S1 displayed the greatest biomechanical stability of the Denis type I sacral fracture FE models. When the S1 pedicle screw insertion point on the affected side is damaged, S2AI-CS1 can be used as an appropriate alternative to S2AI-S1.

No Association of MicroRNA-146a rs2910164 Polymorphism and Risk of Primary Gout Development in Chinese Han Populations: A Case-control Study.

BACKGROUND: Previous studies demonstrated that MicroRNA-146a (miR-146a) plays an important role in the regulation of autoinflammatory diseases including primary gout. The G/C polymorphism (rs2910164) in the precursor sequence of miR-146a caused its stem region to change from G: U to C: U,which can contribute to the susceptibility of human diseases. However, no genetic relevance studies of miR-146a gene polymorphisms to gout have been reported by now. OBJECTIVE: The purpose of this study was to analyze the association between the miR-146a rs2910164 genetic polymorphism and the susceptibility of the Chinese Han population to primary gout. METHODS: 1130 Chinese Han participants (including 606 primary gout patients and 524 gender and age-matched healthy control subjects) were recruited and the 5'exonuclease TaqMan® technology was used to perform miR-146a rs2910164 genotyping. RESULTS: After statistical analysis, no significant differences were observed between gout patients and healthy controls in genotype and allele frequency. CONCLUSION: Our results indicate that there is no evidence for the involvement of the miR-146a rs2910164 polymorphisms in susceptibility to primary gout in the Chinese Han population.

MicroRNA-223 Suppresses IL-1ß and TNF-α Production in Gouty Inflammation by Targeting the NLRP3 Inflammasome.

Introduction: MicroRNA-223 (MiR-223) serves as an important regulator of inflammatory and immune responses and is implicated in several auto-inflammatory disorders. Here, we measured miR-223 expression in acute and intercritical gout patients, after which we used RAW264.7 macrophages transfected with a miR-223 mimic/inhibitor to determine the function of miR-223 in monosodium urate (MSU)-induced gouty inflammation. Methods and Results: MiR-223 was detected among 122 acute gout patients (AG), 118 intercritical gout patients (IG), and 125 healthy subjects (HC). RAW264.7 macrophages were cultured and treated with MSU. Over-expression or under-expression of miR-223 was inducted in RAW264.7 macrophages to investigate the function of miR-223. Real-time quantitative PCR, ELISA and western blotting were used to determine the expression levels of miR-223, cytokines and the NLRP3 inflammasome (NLRP3, ASC, and caspase-1). MiR-223 expression was significantly decreased in the AG group in comparison with the IG and HC groups (p < 0.001, respectively). Up-regulated expression of miR-223 was observed after acute gout remission in comparison with that observed during gout flares in 30 paired cases (p < 0.001). The abundance of the NLRP3 inflammasome and cytokines was significantly increased after RAW264.7 macrophages were treated with MSU (p < 0.01, respectively), while that of miR-223 was significantly reduced (p < 0.01). Up-regulation of miR-223 decreased the concentrations of IL-1ß and TNF-α, as well as the NLRP3 inflammasome expression (p < 0.01, respectively), while IL-37 and TGF-ß1 levels were unchanged (p > 0.05, respectively). Under-expression of miR-223 increased the concentrations of IL-1ß and TNF-α, as well as NLRP3 inflammasome expression (p < 0.01, respectively), while IL-37 and TGF-ß1 levels were not influenced (p > 0.05, respectively). Conclusion: These findings suggest that miR-223 provides negative feedback regulation of the development of gouty inflammation by suppressing production of IL-1ß and TNF-α, but not by regulating IL-37 and TGF-ß1. Moreover, miR-223 regulates cytokine production by targeting the NLRP3 inflammasome.

LncRNAs Landscape in the patients of primary gout by microarray analysis.

To determine the expression profile and clinical significance of long non-coding RNAs (lncRNAs) in peripheral blood mononuclear cells (PBMCs) of patients with primary gout and healthy control subjects. Human lncRNA microarrays were used to identify the differentially expressed lncRNAs and mRNAs in primary gout patients (n = 6) and healthy control subjects (n = 6). Bioinformatics analyses were performed to predict the roles of differently expressed lncRNAs and mRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression levels of 8 lnRNAs in 64 primary gout patients and 32 healthy control subjects. Spearman's correlation was used to analyze the correlation between these eight lncRNAs and the laboratory values of gout patients. A receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic value of the lncRNAs identified in gout. The microarray analysis identified 1479 differentially expressed lncRNAs (879 more highly expressed and 600 more lowly expressed), 862 differentially expressed mRNAs (390 more highly expressed and 472 more lowly expressed) in primary gout (fold change > 2, P < 0.05), respectively. The bioinformatic analysis indicated that the differentially expressed lncRNAs regulated the abnormally expressed mRNAs, which were involved in the pathogenesis of gout through several different pathways. The expression levels of TCONS_00004393 and ENST00000566457 were significantly increased in the acute gout flare group than those in the intercritical gout group or healthy subjects (P<0.01). Moreover, inflammation indicators were positive correlated with TCONS_00004393 and ENST00000566457 expression levels. The areas under the ROC curve of ENST00000566457 and NR-026756 were 0.868 and 0.948, respectively. Our results provide novel insight into the mechanisms of primary gout, and reveal that TCONS_00004393 and ENST00000566457 might be as candidate targets for the treatment of gout flare; ENST00000566457 and NR-026756 could effectively discriminate between the gout and the healthy control groups.

Treatment of pelvic haemophilic pseudotumour: A retrospective study.

BACKGROUND: The incidence of a pelvic haemophilic pseudotumour is very low and is rarely seen in the clinic. Due to the lack of clear treatment standards, patients often suffer from the condition over a protracted period. The aim of this retrospective study was to present our institutional experience in the treatment of pelvic haemophilic pseudotumours over the past 8 years. METHODS: We retrospectively analysed patients with a pelvic haemophilic pseudotumour who were treated in the Nanfang hospital between February 2012 and December 2019. The type and severity of haemophilia, the presence of inhibitors, comorbidities, pseudotumour imaging data, treatment and follow-up results were recorded and analysed. RESULTS: Pelvic pseudotumours were identified in seven patients with haemophilia. Three patients had severe haemophilia, three had moderate haemophilia, one had mild haemophilia and inhibitors were present in two patients. Transfusion-related infectious diseases were noted in three patients. Spontaneous rupture and infection of the pseudotumour occurred in five patients. In addition, five patients underwent surgical treatment, two of whom healed well, two patients suffered recurrence of the pseudotumour, and one patient developed a postoperative haematoma twice. Two patients were treated conservatively, one of whom was unable to walk because of progression of the disease, while the other died from severe bleeding and infection. CONCLUSIONS: Once a pelvic haemophilic pseudotumour is diagnosed, surgical resection should be performed as soon as possible. A delay in diagnosis and suboptimal treatment may lead to complications of the pelvic haemophilic pseudotumour.

Autophagy dysfunction may be involved in the pathogenesis of ankylosing spondylitis.

The present study aimed to investigate the expression and significance of the mRNA of genes associated with autophagy and long non-coding RNA (lncRNA) GAS5 in peripheral blood mononuclear cells (PBMCs) of patients with ankylosing spondylitis (AS). The mRNA levels of microtubule-associated protein light chain 3 (LC3), Beclin1, autophagy-related gene (ATG)3, ATG5, ATG12, ATG 16 ligand 1 (ATG16L1) and lncRNA growth arrest-specific 5 (GAS5) in PBMCs from 60 patients with AS and 30 healthy controls (HC) were examined by reverse transcription-quantitative PCR. The correlations between the levels of LC3, Beclin1, ATG3, ATG5, ATG12 and ATG16L1 mRNA as well as lncRNA GAS5 levels with disease activity and laboratory parameters in patients with AS were determined by Spearman correlation analysis. In addition, the diagnostic value of lncRNA GAS5 for AS was explored through establishing a receiver operating characteristic (ROC) curve. The results indicated that, compared to the HCs, patients with AS had lower expression levels of LC3, ATG5, ATG12, ATG16L1 and lncRNA GAS5 in their PBMCs. Compared with those in patients with inactive AS, the levels of ATG5 and ATG12 were lower than those in patients with active AS. Of note, ATG5 and ATG12 mRNA levels were negatively correlated with disease activity indexes. lncRNA GAS5 was positively correlated with the expression of Beclin1, ATG3, ATG5, ATG12 and ATG16L1. The area under the ROC curve for the use of lncRNA GAS5 expression to diagnose AS was 0.808 with a 95% CI of 0.714-0.902. In conclusion, patients with AS had decreased expression of genes associated with autophagy and lncRNA GAS5. The extent of the reduction in ATG5 and ATG12 expression levels in patients with AS was correlated with the disease severity and activity. Furthermore, lncRNA GAS5 was a diagnostic indicator of AS.

[Neuropeptide Y Y1 receptor antagonist PD160170 promotes osteogenic differentiation of rat bone marrow mesenchymal stem cells in vitro and femoral defect repair in rats].

OBJECTIVE: To investigate the effects of neuropeptide Y (NPY) Y1 receptor antagonist PD160170 in promoting osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and accelerating healing of femoral defect in rats. METHODS: The third generation of rat BMSCs were treated with PBS (control) or 10-6, 10-7, or 10-8 mol/L NPY Y1 receptor antagonist PD160170. After 7 and 14 days of treatment, the cells were examined for osteogenic differentiation with alkaline phosphatase (ALP) and alizarin red staining. At 7 and 21 days of treatment, the mRNA and protein expressions of collagen type I (COLI), osteocalcin (OCN) and Runt-related transcription factor 2 (Runx2) in the cells were detected using q-PCR and Westem Blotting. In a male SD rat model (body weight 300∓20 g) of bilateral femoral condyle defects (2.5 mm in diameter), the effect of daily local injection of 0.2 mL PD160170 (10-6 and 10-8 mol/L, for 28 consecutive days) in promoting bone defect repair was evaluated with micro-CT scans. RESULTS: ALP and alizarin red staining showed that the BMSCs treated with PD160170, at the optimal concentration of 10-8 mol/L, contained more intracellular cytoplasmic brown particles and mineralized nodules in extracellular matrix than PBS-treated cells. PD160170 (10-8 mol/L) significantly up-regulated the mRNA and protein expressions of COLI at day 7 and those of OCN and Runx2 at day 21 (P<0.05). In the rat models of femoral bone defect, the volume/tissue volume ratio, bone mineral density and the number of bone trabeculae were significantly greater in 10-6 mol/L PD160170 group than in the control group (P<0.05), but the bone trabecular thickness (P=0.07) and bone volume (P=0.35) were similar between the two groups. CONCLUSION: NPY Y1 receptor antagonist PD160170 can promote osteogenic differentiation of BMSCs and healing of femoral defects in rats, suggesting the potential of therapeutic strategies targeting NPY Y1 receptor signaling in the prevention and treatment of bone fracture and osteoporosis.

Three dimensionally ordered macroporous Ce(1-x)Zr(x)O(2) solid solutions for diesel soot combustion.

The microstructure with open, interconnected macropores of 3DOM Ce(1-x)Zr(x)O(2), successfully prepared using PMMA colloidal crystal as template and cerium nitrate and zirconium oxide chloride as raw materials, facilitates the contact between soot and catalysts and results in much higher catalytic activity for diesel soot combustion than the corresponding disordered macroporous catalysts.