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Rheumatoid arthritis (RA) is a chronic autoimmune disease that can cause destruction of cartilage and bone's extracellular matrix. Bromodomain 4 (BRD4), as a transcriptional and epigenetic regulator, plays a key role in cancer and inflammatory diseases. While, the role of BRD4 in bone destruction in RA has not been extensively reported. Our study aimed to investigate the effect of BRD4 on the bone destruction in RA and, further, its mechanism in the pathogenesis of the disease. In this study, receiving approval from the Ethical Committee of the Affiliated Hospital of Qingdao University, we evaluated synovial tissues from patients with RA and OA for BRD4 expression through advanced techniques such as immunohistochemistry, quantitative real-time PCR (qRT-PCR), and Western blotting. We employed a collagen-induced arthritis (CIA) mouse model to assess the therapeutic efficacy of the BRD4 inhibitor JQ1 on disease progression and bone destruction, supported by detailed clinical scoring and histological examinations. Further, in vitro osteoclastogenesis assays using RAW264.7 macrophages, facilitated by TRAP staining and resorption pit assays, provided insights into the mechanistic effects of JQ1 on osteoclast function. Statistical analysis was rigorously conducted using SPSS, applying Kruskal-Wallis, one-way ANOVA, and Student's t-tests to validate the data. In our study, we found that BRD4 expression significantly increased in the synovial tissues of RA patients and the ankle joints of CIA mice, with JQ1, a BRD4 inhibitor, effectively reducing inflammation, arthritis severity (p < 0.05), and bone erosion. Treatment with JQ1 not only improved bone mass and structural integrity in CIA mice but also downregulated osteoclast-related gene expression and the RANKL/RANK signaling pathway, indicating a suppression of osteolysis. Furthermore, in vitro assays demonstrated that JQ1 markedly inhibited osteoclast differentiation and function, underscoring the pivotal role of BRD4 in osteoclastogenesis and its potential as a target for therapeutic intervention in RA-induced bone destruction. Our study concludes that targeting BRD4 with the inhibitor JQ1 significantly mitigates inflammation and bone destruction in rheumatoid arthritis, suggesting that inhibition of BRD4 may be a potential therapeutic strategy for the treatment of bone destruction in RA.
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High-altitude pulmonary edema (HAPE) is a deadly form of altitude sickness, and there is no effective treatment for HAPE. Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cell isolated from dental pulp tissues and possess various functions, such as anti-inflammatory and anti-oxidative stress. DPSCs have been used to treat a variety of diseases, but there are no studies on treating HAPE. In this study, Sprague-Dawley rats were exposed to acute low-pressure hypoxia to establish the HAPE model, and SOD1-modified DPSCs (DPSCsHiSOD1) were administered through the tail vein. Pulmonary arterial pressure, lung water content (LWC), total lung protein content of bronchoalveolar lavage fluid (BALF) and lung homogenates, oxidative stress, and inflammatory indicators were detected to evaluate the effects of DPSCsHiSOD1 on HAPE. Rat type II alveolar epithelial cells (RLE-6TN) were used to investigate the effects and mechanism of DPSCsHiSOD1 on hypoxia injury. We found that DPSCs could treat HAPE, and the effect was better than that of dexamethasone treatment. SOD1 modification could enhance the function of DPSCs in improving the structure of lung tissue, decreasing pulmonary arterial pressure and LWC, and reducing the total lung protein content of BALF and lung homogenates, through anti-oxidative stress and anti-inflammatory effects. Furthermore, we found that DPSCsHiSOD1 could protect RLE-6TN from hypoxic injury by reducing the accumulation of reactive oxygen species (ROS) and activating the Nrf2/HO-1 pathway. Our findings confirm that SOD1 modification could enhance the anti-oxidative stress ability of DPSCs through the Nrf2/HO-1 signalling pathway. DPSCs, especially DPSCsHiSOD1, could be a potential treatment for HAPE. Schematic diagram of the antioxidant stress mechanism of DPSCs in the treatment of high-altitude pulmonary edema. DPSCs can alleviate oxidative stress by releasing superoxide dismutase 1, thereby reducing ROS production and activating the Nrf2/HO-1 signalling pathway to ameliorate lung cell injury in HAPE.
Subject(s)
Altitude Sickness , Dental Pulp , NF-E2-Related Factor 2 , Oxidative Stress , Rats, Sprague-Dawley , Superoxide Dismutase-1 , Animals , Dental Pulp/cytology , Dental Pulp/metabolism , NF-E2-Related Factor 2/metabolism , Rats , Superoxide Dismutase-1/metabolism , Superoxide Dismutase-1/genetics , Altitude Sickness/therapy , Altitude Sickness/metabolism , Male , Stem Cells/metabolism , Disease Models, Animal , Signal Transduction , Pulmonary Edema/metabolism , Pulmonary Edema/therapy , Hypertension, Pulmonary/therapy , Hypertension, Pulmonary/metabolism , Humans , Heme Oxygenase (Decyclizing)/metabolism , Heme Oxygenase-1/metabolism , Heme Oxygenase-1/geneticsABSTRACT
BACKGROUND: Atherosclerosis (AS), a chronic inflammatory disease of blood vessels, is a major contributor to cardiovascular disease. Dental pulp stem cells (DPSCs) are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflammation-related diseases. Hepatocyte growth factor (HGF) is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune diseases. AIM: To modify DPSCs with HGF (DPSC-HGF) and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout (ApoE-/-) mouse model and an in vitro cellular model. METHODS: ApoE-/- mice were fed with a high-fat diet (HFD) for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs (DPSC-Null) through tail vein at weeks 4, 7, and 11, respectively, and the therapeutic efficacy and mechanisms were analyzed by histopathology, flow cytometry, lipid and glucose measurements, real-time reverse transcription polymerase chain reaction (RT-PCR), and enzyme-linked immunosorbent assay at the different time points of the experiment. An in vitro inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells (HAOECs), and indirect co-cultured with supernatant of DPSC-Null (DPSC-Null-CM) or DPSC-HGF-CM, and the effect and mechanisms were analyzed by flow cytometry, RT-PCR and western blot. Nuclear factor-κB (NF-κB) activators and inhibitors were also used to validate the related signaling pathways. RESULTS: DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors, and the percentage of macrophages in the aorta, and DPSC-HGF treatment had more pronounced effects. DPSCs treatment had no effect on serum lipoprotein levels. The FACS results showed that DPSCs treatment reduced the percentages of monocytes, neutrophils, and M1 macrophages in the peripheral blood and spleen. DPSC-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tumor necrosis factor-α stimulated HAOECs and regulated M1 polarization and inflammatory factor expression in lipopolysaccharide-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway. CONCLUSION: This study suggested that DPSC-HGF could more effectively ameliorate AS in ApoE-/- mice on a HFD, and could be of greater value in stem cell-based treatments for AS.
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The activated persulfate (PS) process could produce sulfate radical (SO4·-) and rapidly degrade organic pollutants. The application of Fe3O4 as a promising PS activator was limited due to the rapid conversion of Fe2+ to Fe3+ on its surface. Mo4+ on MoS2 surface could be used as a reducing site to convert Fe3+ to Fe2+, but the separation and recovery of MoS2 was complex. In this study, MoS2/Fe3O4 was prepared to accelerate the Fe3+/Fe2+ cycle on Fe3O4 surface and achieved efficient separation of MoS2. The results showed that MoS2/Fe3O4 was more effective for PS activation compared to Fe3O4 or MoS2, with a removal efficiency of 91.8% for 20 mg·L-1 tetracycline (TC) solution under the optimal conditions. Fe2+ and Mo4+ on MoS2/Fe3O4 surface acted as active sites for PS activation with the generation of SO4â¢-, â¢OH, â¢O2-, and 1O2. Mo4+ acted as an electron donor to promote the Fe3+/Fe2+ cycling and thus improved the PS activation capability of MoS2/Fe3O4. The degradation pathways of TC were inferred as hydroxylation, ketylation of dimethylamino group and C-N bond breaking. This study provided a promising activated persulfate-based advanced oxidation process for the efficient degradation of TC by employing MoS2/Fe3O4 as an effective activator.
Subject(s)
Molybdenum , Water Pollutants, Chemical , Tetracycline/analysis , Oxidation-Reduction , Anti-Bacterial Agents , Magnetic Phenomena , Water Pollutants, Chemical/chemistryABSTRACT
Due to their uncontrollable assembly and crystallization process, the synthesis of mesoporous metal oxide single crystals remains a formidable challenge. Herein, we report the synthesis of single-crystal-like mesoporous Li2TiSiO5 by using soft micelles as templates. The key lies in the atomic-scale self-assembly and step-crystallization processes, which ensure the formation of single-crystal-like mesoporous Li2TiSiO5 microparticles via an oriented attachment growth mechanism under the confinement of an in-situ formed carbon matrix. The mesoporous Li2TiSiO5 anode achieves a superior rate capability (148 mAh g-1 at 5.0 A g-1) and outstanding long-term cycling stability (138 mAh g-1 after 3000 cycles at 2.0 A g-1) for lithium storage as a result of the ultrafast Li+ diffusion caused by penetrating mesochannels and nanosized crystal frameworks (5-10 nm). In comparison, bulk Li2TiSiO5 exhibits poor rate capability and cycle performance due to micron-scale diffusion lengths. This method is very simple and reproducible, heralding a new way of designing and synthesizing mesoporous single crystals with controllable frameworks and chemical functionalities.
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[This corrects the article DOI: 10.3389/fmicb.2023.1287468.].
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Introduction: The intricate interplay between gut microbiota and hyperuricemia remains a subject of growing interest. However, existing studies only provided snapshots of the gut microbiome at single time points, the temporal dynamics of gut microbiota alterations during hyperuricemia progression and the intricate interplay between the gut barrier and microbiota remain underexplored. Our investigation revealed compelling insights into the dynamic changes in both gut microbiota and intestinal barrier function throughout the course of hyperuricemia. Methods: The hyperuricemia mice (HY) were given intragastric administration of adenine and potassium oxalate. Gut microbiota was analyzed by 16S rRNA sequencing at 3, 7, 14, and 21 days after the start of the modeling process. Intestinal permeability as well as LPS, TNF-α, and IL-1ß levels were measured at 3, 7, 14, and 21 days. Results: We discovered that shifts in microbial community composition occur prior to the onset of hyperuricemia, key bacterial Bacteroidaceae, Bacteroides, and Blautia exhibited reduced levels, potentially fueling microbial dysbiosis as the disease progresses. During the course of hyperuricemia, the dynamic fluctuations in both uric acid levels and intestinal barrier function was accompanied with the depletion of key beneficial bacteria, including Prevotellaceae, Muribaculum, Parabacteroides, Akkermansia, and Bacteroides, and coincided with an increase in pathogenic bacteria such as Oscillibacter and Ruminiclostridium. This microbial community shift likely contributed to elevated lipopolysaccharide (LPS) and pro-inflammatory cytokine levels, ultimately promoting metabolic inflammation. The decline of Burkholderiaceae and Parasutterella was inversely related to uric acid levels, Conversely, key families Ruminococcaceae, Family_XIII, genera Anaeroplasma exhibited positive correlations with uric acid levels. Akkermansiaceae and Bacteroidaceae demonstrating negative correlations, while LPS-containing microbiota such as Desulfovibrio and Enterorhabdus exhibited positive correlations with intestinal permeability. Conclusion: In summary, this study offers a dynamic perspective on the complex interplay between gut microbiota, uric acid levels, and intestinal barrier function during hyperuricemia progression. Our study suggested that Ruminiclostridium, Bacteroides, Akkermansiaceae, Bilophila, Burkholderiaceae and Parasutterella were the key bacteria that play vital rols in the progress of hyperuricemia and compromised intestinal barrier, which provide a potential avenue for therapeutic interventions in hyperuricemia.
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Introduction: Rebound pain, transient and acute postoperative pain after the disappearance of regional block anesthesia, has been a concern in recent years. Insufficient preemptive analgesia and hyperalgesia induced by regional block are the main mechanisms. At present, the evidence for the treatment of rebound pain is limited. The esketamine, as an antagonist of the N-methyl-D-aspartate receptor, has been proven to prevent hyperalgesia. Therefore, this trial aims to evaluate the impact of esketamine on postoperative rebound pain in patients undergoing total knee arthroplasty. Methods/design: This study is a single-center, prospective, double-blind, randomized, placebo-controlled trial. Participants who plan to undergo total knee arthroplasty will be randomly assigned to the esketamine group (N = 178) and placebo group (N = 178) in a ratio of 1:1. This trial aims to evaluate the impact of esketamine on postoperative rebound pain in patients undergoing total knee arthroplasty. The primary outcome of this trial is the incidence of rebound pain within 12 h after the operation in the esketamine group and the placebo group. The secondary outcome will be to compare (1) the incidence of rebound pain 24 h after the operation; (2) the time to enter the pain cycle for the first time within 24 h after the procedure; (3) the first time of rebound pain occurred within 24 h after surgery; (4) the modified rebound pain score; (5) NRS score under rest and exercise at different time points; (6) the cumulative opioid consumption at different time points; (7) patient's prognosis and knee joint function evaluation; (8) blood glucose and cortisol concentration; (9) patient's satisfaction score; (10) adverse reactions and adverse events. Discussion: The effect of ketamine on preventing postoperative rebound pain is contradictory and uncertain. The affinity of esketamine to the N-methyl-D-aspartate receptor is about four times higher than levo-ketamine, the analgesic effect is 3 times higher than levo-ketamine, and there are fewer adverse mental reactions. To our knowledge, there is no randomized controlled trial to verify the impact of esketamine on postoperative rebound pain in patients undergoing total knee arthroplasty. Therefore, this trial is expected to fill an important gap in relevant fields and provide novel evidence for individualized pain management. Clinical Trial Registration: http://www.chictr.org.cn, identifier ChiCTR2300069044.
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Multi-chambered architectures have attracted much attention due to the ability to establish multifunctional partitions in different chambers, but manipulating the chamber numbers and coupling multi-functionality within the multi-chambered mesoporous nanoparticle remains a challenge. Herein, we propose a nanodroplet remodeling strategy for the synthesis of hierarchical multi-chambered mesoporous silica nanoparticles with tunable architectures. Typically, the dual-chambered nanoparticles with a high surface area of ~469 m2 g-1 present two interconnected cavities like a calabash. Furthermore, based on this nanodroplet remodeling strategy, multiple species (magnetic, catalytic, optic, etc.) can be separately anchored in different chamber without obvious mutual-crosstalk. We design a dual-chambered mesoporous nanoreactors with spatial isolation of Au and Pd active-sites for the cascade synthesis of 2-phenylindole from 1-nitro-2-(phenylethynyl)benzene. Due to the efficient mass transfer of reactants and intermediates in the dual-chambered structure, the selectivity of the target product reaches to ~76.5%, far exceeding that of single-chambered nanoreactors (~41.3%).
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A sulfhydryl monomicelles interfacial assembly strategy is presented for the synthesis of fully exposed single-atom-layer Pt clusters on 2D mesoporous TiO2 (SAL-Pt@mTiO2 ) nanosheets. This synthesis features the introduction of the sulfhydryl group in monomicelles to finely realize the controllable co-assembly process of Pt precursors within ordered mesostructures. The resultant SAL-Pt@mTiO2 shows uniform SAL Pt clusters (≈1.2â nm) anchored in ultrathin 2D nanosheets (≈7â nm) with a high surface area (139â m2 g-1 ), a large pore size (≈25â nm) and a high dispersion (≈99 %). Moreover, this strategy is universal for the synthesis of other SAL metal clusters (Pd and Au) on 2D mTiO2 with high exposure and accessibility. When used as a catalyst for hydrogenation of 4-nitrostyrene, the SAL-Pt@mTiO2 shows a high catalytic activity (TOF up to 2424â h-1 ), 100 % selectivity for 4-aminostyrene, good stability, and anti-resistance to thiourea poisoning under relatively mild conditions (25 °C, 10â bar).
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BACKGROUND: This study aimed to compare the mid-term clinical and radiographic outcomes between medial-pivotal (MP) insert and double-high (DH) insert used under the cruciate-retaining condition in ADVANCE® total knee arthroplasty (TKA). METHODS: The follow-up was conducted for 158 consecutive patients who underwent unilateral ADVANCE® TKA from January 2011 to April 2014. Eighty-four MP inserts and 74 DH inserts were used under cruciate-retaining conditions. A 1:1 propensity score matching (PSM) analysis was performed between MP inserts and DH inserts to compare the clinical and radiographic outcomes. RESULTS: After a 1:1 PSM, 120 patients (60 pairs) were matched between the MP and DH inserts groups. The baseline demographic parameters and clinical scores were comparable between the two groups. The postoperative clinical outcomes at an averaged 8-year follow-up of both groups were significantly improved. The range of motion (ROM) of the DH group was better than that of the MP group, and equivalent Knee Society Function Score (KSFS) between the two groups was found. However, the Knee Society Score (KSS), Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, and Forgotten Joint Score (FJS) of the MP group were found to be significantly superior to those of the DH group. Comparable complication and revision rates were observed between the two groups. The radiographic results were also equally good between MP and DH groups. CONCLUSIONS: Although the mid-term clinical and radiographic outcomes of the DH inserts are fairly good, the clinical scores of the DH group were worse than those of the MP group.
Subject(s)
Arthroplasty, Replacement, Knee , Knee Prosthesis , Osteoarthritis, Knee , Arthroplasty, Replacement, Knee/adverse effects , Arthroplasty, Replacement, Knee/methods , Follow-Up Studies , Humans , Knee Joint/diagnostic imaging , Knee Joint/surgery , Osteoarthritis, Knee/diagnostic imaging , Osteoarthritis, Knee/surgery , Propensity Score , Prosthesis Design , Range of Motion, ArticularABSTRACT
Pseudomonas aeruginosa is one of the most important foodborne pathogens that can persist in leafy green vegetables and subsequently produce biofilms. In this study, the synergistic effect of thymoquinone and nisin in reducing biofilm formation of P. aeruginosa on lettuce was evaluated, and their anti-virulence and anti-biofilm mechanisms were also investigated. At concentrations ranging from 0.5 to 2 mg/ml, thymoquinone inhibited the production of autoinducers and virulence factors, and enhanced the susceptibility of P. aeruginosa biofilms to nisin as evidenced by the scanning electron microscopy and confocal laser scanning microscopy. Integrated transcriptomics, metabolomics, and docking analyses indicated that thymoquinone treatment disrupted the quorum sensing (QS) system, altered cell membrane component, and down-regulated the expressions of genes related to virulence, efflux pump, and antioxidation. The changed membrane component and repressed efflux pump system enhanced membrane permeability and facilitated the entrance of nisin into cells, thus improving the susceptibility of biofilms to nisin. The dysfunctional QS and repressed antioxidant enzymes lead to the enhancement of oxidative stress. The enhanced oxidative stress disrupted energy metabolism and protein metabolism and ultimately attenuated the virulence and pathogenicity of P. aeruginosa PAO1. Our study indicated that thymoquinone has the potential to function as a QS-based agent to defend against foodborne pathogens in combination with nisin.
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An aqueous emulsion polymerization self-assembly approach is demonstrated for the first time to synthesize ultrahigh nitrogen containing mesoporous polymer nanospheres, using melamine-formaldehyde resin oligomers as precursors. In the synthesis, change from alkaline to acidic conditions is critical for the formation of monodisperse mesostructured polymer nanospheres. Owing to unique structure of triazine stabilized in the covalent polymeric networks during the pyrolysis process, the derived mesoporous carbon nanospheres possess an ultrahigh nitrogen content (up to 15.6 wt%) even after pyrolysis at 800 °C, which is the highest nitrogen content among mesoporous carbon nanospheres. Furthermore, these monodisperse mesoporous carbon nanospheres possess a high surface area (≈883 m2 g-1 ) and large pore size (≈8.1 nm). As an anode for sodium-ion batteries, the ultrahigh nitrogen-containing mesoporous carbon nanospheres exhibit superior rate capability (117 mAh g-1 at a high current density of 3 A g-1 ) and high reversible capacity (373 mAh g-1 at 0.06 A g-1 ), indicating a promising material for energy storage.
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Functional mesoporous materials have gained tremendous attention due to their distinctive properties and potential applications. In recent decades, the self-assembly of micelles and framework precursors into mesostructures on the liquid-solid, liquid-liquid, and gas-liquid interface has been explored in the construction of functional mesoporous materials with diverse compositions, morphologies, mesostructures, and pore sizes. Compared with the one-phase solution synthetic approach, the introduction of a two-phase interface in the synthetic system changes self-assembly behaviors between micelles and framework species, leading to the possibility for the on-demand fabrication of unique mesoporous architectures. In addition, controlling the interfacial tension is critical to manipulate the self-assembly process for precise synthesis. In particular, recent breakthroughs based on the concept of the "monomicelles" assembly mechanism are very promising and interesting for the synthesis of functional mesoporous materials with the precise control. In this review, we highlight the synthetic strategies, principles, and interface engineering at the macroscale, microscale, and nanoscale for oriented interfacial assembly of functional mesoporous materials over the past 10 years. The potential applications in various fields, including adsorption, separation, sensors, catalysis, energy storage, solar cells, and biomedicine, are discussed. Finally, we also propose the remaining challenges, possible directions, and opportunities in this field for the future outlook.
Subject(s)
Engineering , Micelles , Catalysis , PorosityABSTRACT
Wear particles may induce osteoclast formation and osteoblast inhibition that lead to periprosthetic osteolysis (PPOL) and subsequent aseptic loosening, which is the primary reason for total joint arthroplasty failure. Local bone renin-angiotensin system (RAS) has been found to participate in the pathogenic process of various bone-related diseases via promoting bone resorption and inhibiting bone formation. However, it remains unclear whether and how local bone RAS participates in wear-particle-induced PPOL. In this study, we investigated the potential role of RAS in titanium (Ti) particle-induced osteolysis in vivo and osteoclast and osteoblast differentiation in vitro. We found that the expressions of AT1R, AT2R and ACE in the interface membrane from patients with PPOL and in calvarial tissues from a murine model of Ti-particle-induced osteolysis were up-regulated, but the increase of ACE in the calvarial tissues was abrogated by perindopril. Moreover, perindopril mitigated the Ti-particle-induced osteolysis in the murine model by suppressing bone resorption and increasing bone formation. We also observed in RAW264.7 macrophages that Ang II promoted but perindopril suppressed Ti-particle-induced osteoclastogenesis, osteoclast-mediated bone resorption and expression of osteoclast-related genes. Meanwhile, Ang II enhanced but perindopril repressed Ti-particle-induced suppression of osteogenic differentiation and expression of osteoblast-specific genes in mouse bone marrow mesenchymal stem cells (BMSCs). In addition, local bone RAS promoted Ti-particle-induced osteolysis by increasing bone resorption and decreasing bone formation through modulating the RANKL/RANK and Wnt/ß-catenin pathways. Taken together, we suggest that inhibition of RAS may be a potential approach to the treatment of wear-particle-induced PPOL.
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BACKGROUND: Angiotensin II (Ang II) is associated with rheumatoid arthritis (RA) development. The present study investigated the impact of Ang II on the expression of receptor activator of nuclear factor-κB ligand (RANKL), as well as of nuclear factor of activated T cells cytoplasmic 1 (NFATC1) in RA synovial cells, and explored the underlying mechanism. METHODS: The expression levels of RANKL, NFATC1, and Ang II type 1 receptor (AT1R) were analyzed by RT PCR, western-blot, and/or immunohistochemistry. Western blot was also used to analyze the p38MAPK, JNK, and ERK1/2 pathways. RESULTS: The expressions of RANKL and NFATC1 increased in synovial tissues of RA compared to osteoarthritis (OA) synovial tissues. The expression of RANKL was upregulated by Ang II, and this effect was mitigated by an AT1R blocker but not by an AT2R blocker. Furthermore, Ang II activated the ERK1/2, JNK, and p38MAPK pathways, and this effect was blocked by the AT1R blocker. However, ERK1/2 and JNK inhibitors, but not a p38MAPK inhibitor, blocked Ang II-induced RANKL expression. Ang II also increased the level of NFATC1, and this upregulation was attenuated by AT1R blockade, ERK1/2 and JNK inhibition, and siRNA-mediated RANKL silencing, but not by AT2R blockade or p38MAPK inhibition. CONCLUSION: Our results indicated that Ang II activated the ERK1/2 and JNK pathways via AT1R, thus upregulating RANKL and NFATC1 expressions in RA synovial cells.
Subject(s)
Angiotensin II/pharmacology , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/metabolism , Gene Expression/drug effects , Gene Expression/genetics , MAP Kinase Signaling System/drug effects , MAP Kinase Signaling System/genetics , NFATC Transcription Factors/genetics , NFATC Transcription Factors/metabolism , RANK Ligand/genetics , RANK Ligand/metabolism , Synovial Membrane/cytology , Synovial Membrane/metabolism , Aged , Female , Humans , Male , Middle Aged , Receptor, Angiotensin, Type 1/genetics , Receptor, Angiotensin, Type 1/metabolism , Up-Regulation/drug effectsABSTRACT
Ultrafine nanoparticles with organic-inorganic hybridization have essential roles in myriad applications. Over the past three decades, although various efforts on the formation of organic or inorganic ultrasmall nanoparticles have been made, ultrafine organic-inorganic hybrid nanoparticles have scarcely been achieved. Herein, a family of ultrasmall hybrid nanoparticles with a monodisperse, uniform size is synthesized by a facile thermo-kinetics-mediated copolymer monomicelle approach. These thermo-kinetics-mediated monomicelles with amphiphilic ABC triblock copolymers are structurally robust due to their solidified polystyrene core, endowing them with ultrahigh thermodynamic stability, which is difficult to achieve using Pluronic surfactant-based micelles (e.g., F127). This great stability combined with a core-shell-corona structure makes the monodispersed monomicelles a robust template for the precise synthesis of ultrasmall hybrid nanoparticles with a highly uniform size. As a demonstration, the obtained micelles/SiO2 hybrid nanoparticles display ultrafine sizes, excellent uniformity, monodispersity, and tunable structural parameters (diameters: 24-47 nm and thin shell thickness: 2.0-4.0 nm). Notably, this approach is universal for creating a variety of multifunctional ultrasmall hybrid nanostructures, involving organic/organic micelle/polymers (polydopamine) nanoparticles, organic/inorganic micelle/metal oxides (ZnO, TiO2 , Fe2 O3 ), micelle/hydroxides (Co(OH)2 ), micelle/noble metals (Ag), and micelle/TiO2 /SiO2 hybrid composites. As a proof of concept, the ultrasmall micelle/SiO2 hybrid nanoparticles demonstrate superior toughness as biomimetic materials.
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PURPOSE: The unique medial-pivot (MP) design of ADVANCE® system largely simulates the movement of a normal knee joint and a high mid- and long-term success rate has been reported in limited populations. The aims of this study are to investigate the mid-term clinical outcomes and survivorship based on a large cohort with 1128 cases. METHODS: One thousand seven patients received 1276 ADVANCE® MP TKAs from January 2011 to April 2016 in our institution were retrospectively investigated. The range of motion (ROM), the Knee Society Score (KSS), the Knee Society Function Score (KSFS), the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, and the Forgotten Joint Score (FJS) were used to evaluate clinical outcomes and Kaplan-Meier survival curve was used to calculate the survivorship. RESULTS: In an averaged five year follow-up, the results of 879 patients (1128 knees) were successfully obtained and the clinical outcomes of 1107 knees were recorded. One hundred forty-eight knees (11.6%) were lost to follow-up. Excellent mid-term ROM, KSS, KSFS, and WOMAC score were recorded. A total of 53 complications were identified and most complications were related to the discordance of femoropatellar joint. Taking revision for any reason as end point, the overall survivorship was 99.2% at seven years. When taking all cases lost to follow-up as failures, the survivorship was 83.8% at five years and 50.6% at seven years. CONCLUSION: For MP designs, the intermediate clinical outcomes are good to excellent and the mid-term survivorship related to reasons other than infection is also satisfactory.
Subject(s)
Arthroplasty, Replacement, Knee , Knee Prosthesis , Osteoarthritis, Knee , Follow-Up Studies , Humans , Knee Joint/diagnostic imaging , Knee Joint/surgery , Osteoarthritis, Knee/surgery , Prosthesis Design , Range of Motion, Articular , Retrospective Studies , Survivorship , Treatment OutcomeABSTRACT
OBJECTIVE: The purpose of this study was to explore the mid-and long-term clinical effects of Chinese patients with medial pivot (MP) prosthesis and posterior-stabilized (PS) prosthesis after total knee arthroplasty (TKA), to provide a reference for the recommendation of clinical prostheses. METHODS: A retrospective analysis of 802 patients who received TKA was performed from June 2010 to December 2013. A total of 432 patients received a MP prosthesis (MP group) and 375 patients received a PS prosthesis (PS group). Postoperative range of motion (ROM), clinical scores including the knee scoring system (KSS), the Western Ontario and McMaster Universities osteoarthritis index (WOMAC), the forgotten joint score (FJS), and postoperative complications were compared between the two groups. RESULTS: A total of 527 patients were followed up, including 290 in the MP group and 237 in the PS group. Both groups achieved satisfactory results in terms of KSS score, WOMAC score, and postoperative ROM, which were significantly improved compared with those before surgery, but the difference between the groups was not statistically significant (P > 0.05). The FJS scores of the MP group and the PS group were satisfactory and no significant difference was observed (P = 0.426). Postoperative complications occurred in 5 and 11 patients in the MP group and PS group, respectively. CONCLUSION: The clinical results of TKA with MP or PS in Chinese patients at mid- and long-term are encouraging, and no significant differences were observed between the two types of prostheses. Studies have also shown that both prostheses are safe for Chinese patients.
Subject(s)
Arthroplasty, Replacement, Knee/methods , Knee Joint/surgery , Knee Prosthesis , Osteoarthritis, Knee/surgery , Aged , Aged, 80 and over , Asian People , Female , Humans , Knee Joint/physiopathology , Male , Osteoarthritis, Knee/physiopathology , Postoperative Complications/epidemiology , Range of Motion, Articular , Retrospective Studies , Time Factors , Treatment OutcomeABSTRACT
The renin-angiotensin system contributes to the pathogenesis of rheumatoid arthritis, but that the mechanism is unclear. This study aims to investigate the effect of angiotensin II (Ang II) on osteogenic differentiation of synoviocytes and the underlying mechanism. Ang II was showed to inhibite osteogenic differentiation of synoviocytes, which was mitigated by a Dickkopf-1 (DKK-1) inhibitor. DKK-1 was upregulated by Ang II, which was weakened by the Ang II type 1 receptor (AT1R) blocker, reactive oxygen species (ROS) scavenger, and p38 inhibitor. Ang II increased the levels of AT1R, ROS, and NADPH oxidase (NOX), and the upregulations were mitigated by the AT1R blocker or NOX inhibitor. Furthermore, Ang II activated the p38 pathway, which was blocked by the AT1R blocker, ROS scavenger, or siRNA-MKK3. In brief, these results indicate that Ang II upregulates NOX expression and ROS production via AT1R, activates the MKK3/p38 signaling, and in turn upregulates DKK-1 expression, participating in the inhibition of osteogenic differentiation of synoviocytes.