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Ankylosing spondylitis (AS) is an autoimmune disease with unknown aetiology. To unravel the mechanisms mediating AS pathogenesis, we profiled peripheral blood mononuclear cells (PBMCs) from AS patients and healthy subjects using 10X single-cell RNA sequencing. The frequencies of immune cell subsets were evaluated by flow cytometry. NK cells were purified from PBMCs using isolation kit and were examined for gene expression by RT-qPCR. Plasma levels of cytolytic molecules were examined by enzyme-linked immunosorbent assay. Compared to healthy controls, AS patients showed a significant decrease in total NK cells as well as CD56dim NK subset, whereas CD56bright NK cells were increased. Additionally, impaired expression of cytotoxic genes in NK cells of AS patients was observed by bioinformatics algorithm and verified by RT-qPCR and flow cytometry. Consistent with changes in transcriptomics, we found decreased plasma levels of granzymes, but not granulysin, in AS patients. Furthermore, Pearson correlation analysis revealed a negative correlation between plasma GZMB levels and disease activity (r = -0.5275, p = 0.0358). No correlation was observed between plasma cytolytic molecules and biochemical indexes (ESR and CRP). Our findings uncover altered NK cell subsets and cytotoxic profiles in peripheral circulation of AS patients at single-cell resolution.
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Espondilitis Anquilosante , Antígeno CD56/genética , Citometría de Flujo , Humanos , Células Asesinas Naturales , Leucocitos Mononucleares/metabolismo , RNA-Seq , Espondilitis Anquilosante/metabolismoRESUMEN
BACKGROUND: N6-methyladenosine (m6A) has been identified as the most abundant modification of RNA molecules and the aberrant m6A modifications have been associated with the development of autoimmune diseases. However, the role of m6A modification in ankylosing spondylitis (AS) has not been adequately investigated. Therefore, we aimed to explore the significance of m6A regulator-mediated RNA methylation in AS. METHODS: The methylated RNA immunoprecipitation sequencing (meRIP-seq) and digital RNA sequencing (Digital RNA-seq) were conducted using the peripheral blood mononuclear cells from three AS cases and three healthy controls, to identify genes affected by abnormal RNA methylation. The genes associated with different peaks were cross-referenced with AS-related genes obtained from the GeneCards Suite. Subsequently, the expression levels of shared differentially expressed genes (DEGs) and key m6A regulators in AS were evaluated using data from 68 AS cases and 36 healthy controls from two data sets (GSE25101 and GSE73754). In addition, the results were validated through quantitative polymerase chain reaction (qPCR). RESULTS: The meRIP-seq and Digital RNA-seq analyses identified 28 genes with upregulated m6A peaks but with downregulated expression, and 52 genes with downregulated m6A peaks but with upregulated expression. By intersecting the genes associated with different peaks with 2184 AS-related genes from the GeneCards Suite, we identified a total of five shared DEGs: BCL11B, KAT6B, IL1R1, TRIB1, and ALDH2. Through analysis of the data sets and qPCR, we found that BCL11B and IL1R1 were differentially expressed in AS. Moreover, two key m6A regulators, WTAP and heterogeneous nuclear ribonucleoprotein C, were identified. CONCLUSIONS: In conclusion, the current study revealed that m6A modification plays a crucial role in AS and might hence provide a new treatment strategy for AS disease.
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Adenosina , Metilación de ARN , Espondilitis Anquilosante , Femenino , Humanos , Masculino , Adenosina/análogos & derivados , Adenosina/metabolismo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Leucocitos Mononucleares/metabolismo , ARN/genética , Espondilitis Anquilosante/genéticaRESUMEN
Objective: Chemotherapy-induced mucositis (CIM) significantly impacts clinical outcomes and diminishes the quality of life in patients with gastrointestinal cancer. This study aims to prospectively determine the incidence, severity, and underlying risk factors associated with CIM in this patient population. Methods: To achieve this objective, we introduce a novel Machine Learning-based Toxicity Prediction Model (ML-TPM) designed to analyze the risk factors contributing to CIM development in gastrointestinal cancer patients. Within the winter season spanning from December 15th, 2018 to January 14th, 2019, we conducted in-person interviews with patients undergoing chemotherapy for gastrointestinal cancer. These interviews encompassed comprehensive questionnaires pertaining to patient demographics, CIM incidence, severity, and any supplementary prophylactic measures employed. Results: The study encompassed a cohort of 447 participating patients who provided complete questionnaire responses (100%). Of these, 328 patients (73.4%) reported experiencing CIM during the course of their treatment. Notably, CIM-induced complications led to treatment discontinuation in 14 patients (3%). The most frequently encountered CIM symptoms were diarrhea (41.6%), followed by nausea (37.8%), vomiting (25.1%), abdominal pain (21%), gastritis (10.5%), and oral pain (10.3%). Supplementary prophylaxis was administered to approximately 62% of the patients. The analysis revealed significant correlations between the overall incidence of CIM and gender (p=0.015), number of chemotherapy cycles exceeding one (p=0.039), utilization of platinum-based regimens (p=0.039), and administration of irinotecan (p=0.003). Specifically, the incidence of diarrhea exhibited positive correlations with prior surgical history (p=0.037), irinotecan treatment (p=0.021), and probiotics usage (p=0.035). Conversely, diarrhea incidence demonstrated an adverse correlation with platinum-based treatment (p=0.026). Conclusion: In conclusion, this study demonstrates the successful implementation of the ML-TPM model for automating toxicity prediction with accuracy comparable to conventional physical analyses. Our findings provide valuable insights into the identification of CIM risk factors among gastrointestinal cancer patients undergoing chemotherapy. Furthermore, the results underscore the potential of machine learning in enhancing our understanding of chemotherapy-induced mucositis and advancing personalized patient care strategies.
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OBJECTIVES: Bone marrow mesenchymal stem cells (BMSCs) are instrumental in bone development, metabolism, and marrow microenvironment homeostasis. Despite this, the relevant effects and mechanisms of BMSCs on congenital scoliosis (CS) remain undefined. Herein, it becomes our focus to reveal the corresponding effects and mechanisms implicated. METHODS: BMSCs from CS patients (hereafter referred as CS-BMSCs) and healthy donors (NC-BMSCs) were observed and identified. Differentially expressed genes in BMSCs were analyzed utilizing scRNA-seq and RNA-seq profiles. The multi-differentiation potential of BMSCs following the transfection or infection was evaluated. The expression levels of factors related to osteogenic differentiation and Wnt/ß-catenin pathway were further determined as appropriate. RESULTS: A decreased osteogenic differentiation ability was shown in CS-BMSCs. Both the proportion of LEPR+ BMSCs and the expression level of WNT1-inducible-signaling pathway protein 2 (WISP2) were decreased in CS-BMSCs. WISP2 knockdown suppressed the osteogenic differentiation of NC-BMSCs, while WISP2 overexpression facilitated the osteogenesis of CS-BMSCs via acting on the Wnt/ß-catenin pathway. CONCLUSIONS: Our study collectively indicates WISP2 knockdown blocks the osteogenic differentiation of BMSCs in CS by regulating Wnt/ß-catenin signaling, thus providing new insights into the aetiology of CS.
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Células Madre Mesenquimatosas , Escoliosis , Humanos , beta Catenina/metabolismo , Diferenciación Celular/genética , Regulación hacia Abajo , Células Madre Mesenquimatosas/metabolismo , Osteogénesis/genética , Escoliosis/genética , Escoliosis/metabolismoRESUMEN
Background: Many studies have demonstrated that vitamin D has clinical benefits when used to treat patients with chronic obstructive pulmonary disease (COPD). However, most of these studies have insufficient samples or inconsistent results. The aim of this meta-analysis was to evaluate the effects of vitamin D therapy in patients with COPD. Methods: We performed a comprehensive retrieval in the following electronic databases: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, and Chinese Scientific Journals Database (VIP). Two trained reviewers identified relevant studies, extracted data information, and then assessed the methodical quality by the Cochrane risk of bias assessment tool, independently. Then, the meta-analyses were conducted by RevMan 5.4, binary variables were represented by risks ratio (RR), and continuous variables were represented by mean difference (MD) or standardized mean difference (SMD) to assess the efficacy of vitamin D therapy in patients with COPD. Then, publication bias assessment was conducted by funnel plot analysis. Finally, the quality of evidence was assessed by the GRADE system. Results: A total of 15 articles involving 1598 participants were included in this study. The overall results showed a statistical significance of vitamin D therapy in patients with COPD which can significantly improve forced expiratory volume in 1 second (FEV1) (MD: 5.69, 95% CI: 5.01-6.38,P < 0.00001,I2 = 51%) and FEV1/FVC (SMD:0.49, 95% CI: 0.39-0.60,P < 0.00001,I2 = 84%); and serum 25 (OH)D (SMD:1.21, 95% CI:1.07-1.34,P < 0.00001,I2 = 98%) also increase CD3+ Tcells (MD: 6.67, 95% CI: 5.34-8.00,P < 0.00001,I2 = 78%) and CD4+ T cells (MD: 6.00, 95% CI: 5.01-7.00,P < 0.00001,I2 = 65%); and T lymphocyte CD4+/CD8+ ratio (MD: 0.41, 95% CI: 0.20-0.61,P = 0.0001,I2 = 95%) obviously decrease CD8+ Tcells(SMD: -0.83, 95% CI: -1.05- -0.06,P < 0.00001,I2 = 82%), the times of acute exacerbation (RR: 0.40, 95% CI: 0.28-0.59,P < 0.00001,I2 = 0%), and COPD assessment test (CAT) score (MD: -3.77, 95% CI: -5.86 - -1.68,P = 0.0004,I2 = 79%). Conclusions: Our analysis indicated that vitamin D used in patients with COPD could improve the lung function (FEV1 and FEV1/FVC), the serum 25(OH)D, CD3+ T cells, CD4 + T cells, and T lymphocyte CD4+/CD8+ ratio and reduce CD8+ T cells, acute exacerbation, and CAT scores.
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Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Vitamina D/uso terapéutico , Biología Computacional , Volumen Espiratorio Forzado/efectos de los fármacos , Humanos , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Pruebas de Función Respiratoria , Subgrupos de Linfocitos T/efectos de los fármacos , Subgrupos de Linfocitos T/inmunología , Capacidad Vital/efectos de los fármacosRESUMEN
Inhibitory receptors (IRs) play an indispensable role in regulating T cell activation and expansion. This study is aimed at exploring the correlation between IRs and ankylosing spondylitis (AS). Bioinformatics analysis of two datasets (GSE25101 and GSE73754), including 68 AS cases and 36 healthy controls, demonstrated that "T cell receptor signaling pathway" was significantly enriched, and two IRs (CD112R and CD96) were downregulated in AS cases. Real-time Quantitative PCR Detecting System (qPCR) analysis confirmed the decreased expression of CD112R and CD96 in the peripheral blood of AS patients. Flow cytometry demonstrated that the frequency of CD96-positive cells among CD4 T cells in AS patients was significantly reduced and that expressed on the cells was also significantly lower than the healthy controls. In addition, the expression of CD96 was altered on human primary CD4 T cells extracted from 3 healthy volunteers and cocultured with allogeneic dendritic cells (DCs). Also, low expression of CD96 elevated the phosphorylation of ERK in CD4 T cells and increased the level of TNF-α, IL-23, IL-17A, IL-6, and IFN-γ in the cell culture supernatant. These results suggested that CD96 is crucial for the pathogenesis of AS and may be a potential target in the treatment of the disease.
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Linfocitos T CD4-Positivos , Espondilitis Anquilosante , Antígenos CD/metabolismo , Regulación hacia Abajo , Humanos , Activación de Linfocitos , Espondilitis Anquilosante/metabolismoRESUMEN
This research develops a simple template assisted sol-gel process for preparing porous TiO2 for a high performance humidity sensor. Tetraethyl orthosilicate (TEOS) as a template was directly introduced into TiO2 sol formed by the hydrolysis and condensation of titanium alkoxide; the following calcination led to the formation of TiO2-SiO2 composite, and the selective removal of SiO2 by dilute HF solution led to the formation of porous structure in TiO2. The resulting porous TiO2-based sensor exhibits high sensitivity and linear response in the wide relative humidity (RH) range of 11%-95%, with an impedance variation of four orders of magnitude to humidity change. Moreover, it exhibits a rapid and highly reversible response characterized by a very small hysteresis of <1% RH and a short response-recovery time (5 s for adsorption and 8 s for desorption), and a 30-day stability test also confirms its long-term stability. Compared with pure TiO2 prepared by the conventional sol-gel method, our product shows remarkably improved performance and good prospect for a high performance humidity sensor. The complex impedance spectra were used to elucidate its humidity sensing mechanism in detail.
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BACKGROUND: The pathogenesis of rheumatoid arthritis (RA) is complex. This study aimed to identify diagnostic biomarkers and transcriptional regulators that underlie RA based on bioinformatics analysis and experimental verification. MATERIAL AND METHODS: We applied weighted gene co-expression network analysis (WGCNA) to analyze dataset GSE55457 and obtained the key module most relevant to the RA phenotype. We then conducted gene function annotation, gene set enrichment analysis (GSEA) and immunocytes quantitative analysis (CIBERSORT). Moreover, the intersection of differentially expressed genes (DEGs) and genes within the key module were entered into the STRING database to construct an interaction network and to mine hub genes. We predicted microRNA (miRNA) using a web-based tool (miRDB). Finally, hub genes and vital miRNAs were validated with independent GEO datasets, RT-qPCR and Western blot. RESULTS: A total of 367 DEGs were characterized by differential expression analysis. The WGCNA method divided genes into 14 modules, and we focused on the turquoise module containing 845 genes. Gene function annotation and GSEA suggested that immune response and inflammatory signaling pathways are the molecular mechanisms behind RA. Nine hub genes were screened from the network and seven vital regulators were obtained using miRNA prediction. CIBERSORT analysis identified five cell types enriched in RA samples, which were closely related to the expression of hub genes. Through ROC curve and RT-qPCR validation, we confirmed five genes that were specific for RA, including CCL25, CXCL9, CXCL10, CXCL11, and CXCL13. Moreover, we selected a representative gene (CXCL10) for Western blot validation. Vital miRNAs verification showed that only the differences in has-miR-573 and has-miR-34a were statistically significant. CONCLUSION: Our study reveals diagnostic genes and vital microRNAs highly related to RA, which could help improve our understanding of the molecular mechanisms underlying the disorder and provide theoretical support for the future exploration of innovative therapeutic approaches.
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Background. Ankylosing spondylitis (AS) is a chronic disease in which the column is the main lesion. It is caused by a combination of genetic and environmental factors, mainly involving the axial skeleton, resulting in column rigidity and difficulty in movement, and there may be different degrees of eye, lung, cardiovascular, kidney, and other organ damage. Long-term treatment lacks in ankylosing spondylitis. Wenbu Zhibi granule (WZG) is a prescription handed down from the history of Chinese medicine for thousands of years, which is used to treat the pain of patients with AS and to prevent the further development of the disease. However, there is no scientific evidence based on clinical trials to evaluate the efficacy and safety of WZG for ankylosing spondylitis. Methods/Design. We will conduct a multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of the WZG in the treatment of AS. We will randomly assign 100 patients with active AS to two groups, treated for 16 weeks. The primary efficacy endpoint is the proportion of subjects who reached 40% improvement criteria proposed by Assessment of SpondyloArthritis International Society (ASAS40) at 16 weeks from baseline, the secondary efficacy endpoint includes ASAS20 response rate, ASAS partial remission response rate, 5/6 improvement criteria proposed by ASAS (ASAS5/6) response rate, and change in the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI spine score, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Disease Activity Score (ASDAS), linear Bath Ankylosing Spondylitis Metrology Index (BASMI), ankylosing spondylitis quality of life (ASQoL). In addition, the time points will be set as baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 24 weeks, and 48 weeks. Discussion. The results of this study will elucidate the efficacy and safety of WZG and provide an appropriate treatment option for patients with AS. Trial registration: ClinicalTrials.gov ID: https://clinicaltrials.gov/ct2/show/ChiCTR2000041010. (Chinese Clinical Trail Registry, Registered 16 December 2020, http://www.chictr.org.cn).
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OBJECTIVE: Our objective was to compare the effectiveness of nonbiological artificial liver (NBAL) support, particularly short-term (28-day) survival rates, in patients who underwent treatment using double plasma molecular adsorption system (DPMAS), plasma exchange (PE), or combined PE+DPMAS, in addition to comprehensive physical treatment for different stages of acute-on-chronic liver failure (ACLF). METHODS: We retrospectively reviewed clinical data of 135 patients with ACLF who received NBAL treatment between November 2015 and February 2019. The patients were categorized into PE, DPMAS, and PE+DPMAS groups. Short-term effectiveness of treatment was assessed and compared based on selected clinical findings, laboratory parameters, and liver function markers. RESULTS: Coagulation function improved significantly in all groups after treatment. In the PE and PE+DPMAS groups, prothrombin time decreased to different degrees, whereas plasma thromboplastin antecedent increased significantly after treatment. White blood cell counts increased and platelet counts decreased in all groups after treatment. The model for end-stage liver disease score, Child-Pugh grade, systematic inflammatory syndrome score, and sepsis-related organ failure score decreased in all three groups after treatment. CONCLUSIONS: PE, DPMAS, and PE+DPMAS improved disease indicators in all patients with ACLF. The combined treatment improved the short-term effectiveness of treatment, especially in patients with mild ACLF.
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Insuficiencia Hepática Crónica Agudizada/terapia , Hígado Artificial/efectos adversos , Intercambio Plasmático/métodos , Insuficiencia Hepática Crónica Agudizada/sangre , Insuficiencia Hepática Crónica Agudizada/mortalidad , Adsorción/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Bilirrubina/sangre , Coagulación Sanguínea/fisiología , Femenino , Humanos , Hígado , Masculino , Persona de Mediana Edad , Plasma/metabolismo , Tiempo de Protrombina/métodos , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Spinal cord injury (SCI) is a catastrophic disease associated with damaged neurological structures and has become a significant social and economic burden for the health care system and patients' families. The use of Chinese Herbal Medicine (CHM) to treat SCI has been increasing in recent years. This meta-analysis aimed to investigate the effectiveness of CHM for patients with SCI. Therefore, we included randomized controlled trials (RCTs) of CHM for SCI in seven databases. A total of 26 studies involving 1961 participants were included in this study. No serious heterogeneity or publication bias was observed across each study. The results showed that significant improvements of the American Spinal Injury Association (ASIA)-grading improvement rate ([Formula: see text], [Formula: see text]), clinical effective rate ([Formula: see text], [Formula: see text]), ASIA motor score ([Formula: see text], [Formula: see text]), ASIA sensory score (total) ([Formula: see text], [Formula: see text]), ASIA sensory score (light touch) ([Formula: see text], [Formula: see text]), ASIA sensory score (pinprick) ([Formula: see text], [Formula: see text]), and activities of daily living (ADL) score ([Formula: see text], [Formula: see text]) in CHM group compared with the control group. Among the CHM groups, Buyang Huanwu decoction was the most frequently prescribed herbal formula, while Astragalus membranaceus was the most commonly used single herb. In addition, there were no serious and permanent adverse effects in the two groups. The methodological quality of the most included RCTs was poor and the quality of evidence for the main outcomes was from very low to moderate according to the GRADE system. Current evidence suggests that CHM is an effective and safe treatment for SCI and could be treated as a complementary and alternative option with few side effects. However, considering the low quality, small size, and high risk of the studies identified in this meta-analysis, higher methodological quality, rigorously designed RCTs with large sample sizes are needed to confirm the results.
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Medicamentos Herbarios Chinos/uso terapéutico , Fitoterapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Traumatismos de la Médula Espinal/tratamiento farmacológico , Actividades Cotidianas , Astragalus propinquus , Femenino , Humanos , Masculino , Extractos Vegetales/uso terapéutico , Seguridad , Sensación , Traumatismos de la Médula Espinal/fisiopatología , Resultado del TratamientoRESUMEN
OBJECTIVE: To choose the disease-causing gene in a Chinese pedigree with ankylosing spondylitis (AS) by whole-exome sequencing (WES), and provide theory basis for mechanism of disease. METHODS: Clinical data of AS pedigree were collected, including 2 males, the age were 48 and 18 years old, the course of disease were 23 and 4 years. Whole blood genomic DNA of AS was extracted to perform whole exome sequencing, the results were compared with human databases, common variations which had been reported were wiped out, then non synonymous single nucleotide variants(SNVs) from the family members were combined, and candidate genes was selected initially. RESULTS: Totally 80 G data was obtained from AS family with high quality.By comparing results between patient and normal subject, and filtering with number of biological database, the result showed heterozygous mutation of JAK2 gene 12 exon c.1709 A>G (p.Tyr570Cys) may be the potential disease-causing gene. The variant c.1151T>C of MUC3A gene may be one of the causes of intestinal symptoms in the family members. CONCLUSION: It is feasible to find t candidate gene mutations of AS by Exon sequencing. The mutation c.1709 A>G in gene JAK2 identified by whole exome sequencing might be the pathogenic mutation in this AS pedigree.
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Exoma , Espondilitis Anquilosante , Humanos , Masculino , Mucina 3 , Mutación , Linaje , Secuenciación del ExomaRESUMEN
Density functional theory was used to optimize the geometry structure of two isomers of ginsenoside, Re, 20-(R)-R and 20-(S)-Re. The ginsenoside Re is an active constituent in ginseng. The calculated results show that there is an obvious difference in space structure between 20-(R)-R and 20-(S)-Re. The main reason for that can be the difference in the space orientation of the four constituents in the 20th carbon (chiral), which leads to the different stacking mode and causes the difference in vibrational spectra in the two isomers. The experimental IR and Raman spectra were assigned according to the calculated frequency, theoretical IR intensity and Raman active. The calculated vibrational peaks at 1,541, 1,456 and 1,424 cm(-1) can be used to distinguish the two isomers. The result shows a good agreement between the calculated and the experimental Raman spectra. The vibrational spectra can be used to identify the active constituent in ginseng.
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Ginsenósidos/química , Carbono , Isomerismo , Espectroscopía Infrarroja por Transformada de Fourier , Espectrometría Raman , VibraciónRESUMEN
OBJECTIVE: To observe inhibitory effect of zoledronic acid on polyethylene particle-induced periprosthetic osteolysis model. METHODS: Thirty male adult specific-pathogen-free SD rats (weighted 250 to 300 g) were randomly divided into sham group, model group, and zoledronic acid group, 10 in each group. Modeling were building by titanium screws and polyethylene particles implanted into right femur of rats, sham group and model group were performed hypodermic injection by 0.9% saline with 2 ml/kg, zoledronic acid with 0.1 ml/mg were injected into zoledronic acid group, once a week for 8 weeks. After 8 weeks, right femur specimens were drawn and used to san microstructure of femoral cancellous bone in rats model was examined by Micro-CT, and the images were treated with three-dimension reconstruction and analysis software BMD, BV/TV, Tb.N, Tb.Th, SMI, BS/BV, Tb.Sp and Tb.Pf and other parameters include. RESULTS: According to Micro-CT three-dimensional imaging, BMD in model group was significantly decreased than sham group, bone microstructure damage was serious, bone trabecula changed thinning continuity; while bone microstructure was obviously improved compared with model group and zoledronic acid group. After analyzing Micro-CT parameters of femur microstructure, BMD in model group(0.081±0.020) was significantly decreased than control group(0.160±0.018) and zoledronic acid group(0.125±0.012); BV/TV in model group (10.563±1.070) was obviously lower than control group(27.935±1.834) and zoledronic acid group(14.559±1.258); Tb.N in model group (1.005±0.165) was lower than control group(2.058±0.108) and zoledronic acid group(1.515±0.126); while Tb.Th in model group (0.075±0.016) was decreased than control group(0.158±0.016) and zoledronic acid group(0.124±0.011). Meanwhile, SMI in model group(1.817±0.127) was significantly higher than control group(1.104±0.120) and zoledronic acid group(1.547±0.122); BS/BV in model group(35.784±1.650) was higher than control group(21.506±2.771) and zoledronic acid group(30.399±2.730); Tb.Sp in model group(0.735±0.107) was higher than control group(0.423±0.057) and zoledronic acid group(0.577±0.082), TB.Pf in model group(9.088±1.283) was higher than control group(2.447±0.703) and zoledronic acid group(5.862±1.042). CONCLUSIONS: Zoledronic acid could change bone microstructure of rats to inhibit polyethylene particle-induced bone solution, which provides a scientific basis for prevent bone solution by zoledronic acid as a therapeutic intervention.
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Conservadores de la Densidad Ósea/uso terapéutico , Difosfonatos/uso terapéutico , Imidazoles/uso terapéutico , Osteólisis/prevención & control , Polietileno/efectos adversos , Animales , Densidad Ósea , Masculino , Osteólisis/etiología , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Microtomografía por Rayos X , Ácido ZoledrónicoRESUMEN
Naringin is an abundant flavanone in pomelo, grapefruit as well as lime and its variants, has been shown to exhibit certain antioxidative, anti-inflammatory, anti-cancer and hypoglycemic effects. The aim of the current study was to evaluate the protective effects of naringin against ankylosing spondylitis (AS) and to elucidate the potential underlying mechanism. Firstly, a mouse model of ankylosing spondylitis (AS) was established. Next, osteocalcin (OC), alkaline phosphatase (ALP) and triglyceride (TG) activity values, inflammatory factor and oxidative stress were evaluated in the AS mice. Then, the Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) protein expression levels in the AS mice were investigated using western blot analysis. The results showed that naringin increased OC, ALP and TG activity values in the AS mouse model. Furthermore, inflammatory factor and oxidative stress levels in the AS mice were restrained by treatment with naringin. Furthermore, JAK2 and STAT3 protein expression levels were reduced by treatment with naringin. In conclusion, the present results indicated that the protective effects of naringin against AS are exerted via the induction of ossification, suppression of inflammation and oxidative stress and the downregulation of JAK2/STAT3 in mice.
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OBJECTIVE: To observe the effect and mechanisim of zoledronate sodium on periprosthetic osteolysis in rat induced by polyethylene particles. METHODS: Total 30 adult male SD rats, weighting from 250 to 300 g, were selected and randomly divided into three groups: blank control group, model control group and zoledronate sodium group respectively, 10 animals for each group. No treatment was performed in the blank control group. In model control group and zoledronate sodium group, the modle of periprosthetic osteolysis in rats were made by implanting polyethylene particles and titanium rods into their right femurs. After operation, rats in zoledronate sodium group were administered with zoledronate sodium (0.1 mg/kg each week) through subcutaneous injection for 8 weeks, then the blood was obtained and all experimental animals were sacrificed to get the right femur specimens. The femur BMD, IL-1ß, IL-6, TNF-α, serum TRACP5b and CTX-I were detected. RESULTS: Compared with the model control group, the femur BMD was increased, while IL-1ß, IL-6 and TNF-α were all decreased in zoledronate sodium group; the serum TRACP5b and CTX-I level were both reduced in zoledronate sodium group. CONCLUSION: The zoledronate sodium could effectively inhibit periprosthetic osteolysis in rats induced by polyethylene particles, which might be realized by inhibiting the activity of osteoclasts and the expression of IL-1ß, IL-6 and TNF-α. It provides a new method to treat periprosthetic osteolysis of the artificial joint prosthesis.
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Difosfonatos/uso terapéutico , Imidazoles/uso terapéutico , Prótesis Articulares , Osteólisis/tratamiento farmacológico , Polietileno/farmacología , Animales , Densidad Ósea/efectos de los fármacos , Colágeno Tipo I/análisis , Citocinas/análisis , Masculino , Péptidos/análisis , Ratas , Ratas Sprague-Dawley , Ácido ZoledrónicoRESUMEN
In the search for efficient photocatalysts working under visible light, we have investigated the effect of metal ions (Bi/Co, Fe/Co) codoping on the photocatalytic activity of TiO(2) prepared by stearic acid gel method. UV-vis spectra revealed that doped Co enhanced the absorbency of TiO(2) under visible light, and Bi/Co codoped TiO(2) showed higher absorbance than Fe/Co codoped TiO(2). The photoreaction based on the prepared samples for photodegradation of 20mg/l rhodamine B solution was examined. The results showed that Fe(0.1%)/Co(0.4%) codoped TiO(2) had the highest photoactivity among all as-prepared samples under visible light, though less absorbency of visible light, indicating that the photoactivity not only benefits from absorbency but also relates to the cooperative effect of the two dopants.