Objective To investigate the distribution and alteration of lymphatic vessels and draining function in knee joints of normal and osteoarthritic mice. Methods For the mouse models of osteoarthritis (OA), we used mice with meniscal-ligamentous injury or mice with conditional knockout of the gene for cartilage transforming growth factor β (TGF β) type II receptor. The severity of cartilage loss and joint destruction was assessed histologically. Capillary and mature lymphatic vessels were identified and analyzed using double immunofluorescence staining and a whole-slide digital imaging system. Lymphatic drainage of knee joints was examined using near-infrared lymphatic imaging. Patient joint specimens obtained during total knee or hip arthroplasty were evaluated to verify the content validity of the mouse findings. Results Lymphatic vessels were distributed in soft tissues (mainly around the joint capsule, ligaments, fat pads, and muscles of normal knees). The number of lymphatic vessels, particularly the number of capillaries, was significantly increased in joints of mice with mild OA, while the number of mature lymphatic vessels was markedly decreased in joints of mice with severe OA. OA knees exhibited significantly decreased lymph clearance. The number of both capillary and mature lymphatic vessels was significantly decreased in the joints of patients with OA. Conclusion The whole-slide digital imaging system is a powerful tool, enabling the identification and assessment of lymphatic microvasculature in the entire mouse knee. Lymphatic capillaries and mature vessels are present in various soft tissues around articular spaces. Abnormalities of lymphatic vessels and draining function, including significantly reduced numbers of mature vessels and impaired clearance, are present in OA joints.

represses chondrocyte pyroptosis and relieves cartilage injury in osteoarthritis by inhibiting cathepsin B/Nod-like receptor protein 3, Bioengineered,

Purpose The purpose of this study was to investigate the possible association between single nucleotide polymorphisms (SNPs) rs1800629 (TNF-α -308) and rs361525 (TNF-α -238) of the tumour necrosis factor (TNF)-α gene and susceptibility to osteoarthritis (OA) in the Han Chinese population. Methods The TNF-α -308 and -238 genotypes were determined by TaqMan assay in 200 OA cases and 305 controls. Odds ratios (ORs) for OA and 95 % confidence intervals (CIs) from unconditional logistic regression models were used to evaluate relative risks. Results The frequencies of the allele 'A' of rs1800629 were 16 % and 8.85 % in OA cases and in controls, respectively, and thus the -308A allele had a 1.9612-fold (95 % CI=1.3323-2.8869, P<0.001) increased risk for OA as compared to the -308G allele. However, no significant differences were found in the genotype and allele frequencies for rs361525 between OA and HC groups. Conclusions In the Han Chinese population, the allele 'A' of TNF-α -308 may increase the risk for OA, whereas TNF-α -238 polymorphisms do not play a role in OA patients.

Several studies demonstrate that the bromodomain inhibitor OTX015 has an antitumor activity in cancers. However, translation of these data to molecules suitable for clinical development has yet to be accomplished in multiple myeloma (MM). Here, we identified genes and biologic processes that substantiated the antimyeloma activity of OTX015 with global transcriptomics. OTX015 exerted a strong antiproliferative effect and induced cell cycle arrest in vitro. Gene expression profiling uncovered that OTX015 targeted NF-κB, EGFR, cell cycle regulation, and the cancer proliferation signaling pathway. Gene expression signatures displaying various levels of sensitivity to OTX015 were also identified. The data also showed that oral administration of OTX015 displayed significant antitumor activity in the mice model of disseminated human myeloma. In addition, our study provided the first evidence and rationale that OTX015 could promote osteoblast differentiation of mesenchymal stem cells (MSCs) and inhibited osteoclast formation and resorption in vivo experiments. Herein our results expanded the understanding of the mechanism for BET inhibitors OTX015 in MM. Our study provided an impressive basis for the clinical application of the novel antimyeloma agent OTX015 and uncovered signaling pathways that may play key roles in myeloma cell proliferation.

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Inflammation in bone defect after being implanted scaffold is related to oxidative stress, which is caused mainly by higher concentration of hydrogen peroxide (H2O2). Manganese dioxide (MnO2) can catalyze H2O2 decomposition to decrease excessive H2O2 in the surrounding environment of scaffolds. Furthermore, the oxygen (O2) generated by the decomposition of H2O2 can alleviate the hypoxia caused by insufficient blood supply in bone defects, which is conducive to bone tissue regeneration. In this study, a simple redox method was proposed to deposit MnO2 particles on the surface of 3D printed bioactive glass (BG) scaffolds for the preparation of BG-MnO2 composite scaffolds (BGM), which endows BG-MnO2 scaffolds with the ability of H2O2 scavenging and O2 supply simultaneously. The results showed that the MnO2 content deposited on the surface of BGM scaffolds increased with the increase of potassium permanganate concentration in the reaction solution, and the compressive strength of BGM scaffolds increased with the increase of MnO2 content. However, porosity and degradation rate of these scaffolds with or without MnO2 remained the same. More importantly, BGM scaffolds can continuously catalyze the decomposition of H2O2 to produce O2 in H2O2

An ultrafast laser-induced phase change in gold thin films with different thicknesses has been simulated by the method of coupling the two-temperature model and the molecular dynamics, including transient optical properties. Numerical results show that the decrease of film thickness leads to faster melting in the early nonequilibrium time and a larger melting depth. Moreover, earlier occurrence and a higher rate of resolidification are observed for the thicker film. Further analysis reveals that the mechanism for the thickness-dependent phase change in the films is the fast electron thermal conduction in the nonequilibrium state.

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