ameliorating-osteoarthritis-in-mice-using-silver-nanoparticles

Ameliorating Osteoarthritis in Mice Using Silver Nanoparticles

Knee osteoarthritis (KOA) is one of the most commonly encountered degenerative diseases of the joints in people over 45 years of age. Currently, there are ...

The Third Affiliated Hospital of Sun Yat-sen University

The extensile lateral approach (ELA) has been widely performed for displaced intra-articular calcaneal fractures (DIACFs), and wound complications remain a significant problem. As a minimal incision technique, the sinus tarsi approach (STA) was designed to overcome this disadvantage. There were already many reports about this approach but the conclusions were not completely consistent. Based on the current evidence, we performed this meta-analysis to compare the STA with ELA in the management of DIACF and expected to draw a certain and meaningful conclusion.

Sinus tarsi approach versus extensile lateral approach for displaced intra-articular calcaneal fracture: a meta-analysis of current evidence base.

The extensile lateral approach (ELA) has been considered to be a standard approach for displaced intra-articular calcaneal fractures (DICF) because it provides excellent exposure and allows direct reduction of the depressed posterior facet fragment. But continuous retraction during surgery needs sufficient manpower and may cause ischemia. Failure of rigid fixation of DICF will not allow for early weight bearing and may lead to a loss of reduction. To avoid these disadvantages, this study presents open reduction assisted with an external fixator and internal fixation with a calcaneal locking plate.

Open Reduction Assisted With an External Fixator and Internal Fixation With Calcaneal Locking Plate for Intra-articular Calcaneal Fractures.

An adequate matrix production of nucleus pulposus (NP) cells is an important tissue engineering-based strategy to regenerate degenerative discs. Here, we mainly aimed to investigate the effects and mechanism of mechanical compression (i.e., static compression vs. dynamic compression) on the matrix synthesis of three-dimensional (3D) cultured NP cells in vitro.

Dynamic Compression Promotes the Matrix Synthesis of Nucleus Pulposus Cells Through Up-Regulating N-CDH Expression in a Perfusion Bioreactor Culture.

The aim of the present study was to investigate the expression of cell division cycle gene 2 () in osteosarcoma tissues and its clinical significance. Specimens of cancer tissues, paracancerous tissues and serum from 47 patients hospitalized at the Department of Orthopedics at The Third Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) from January, 2010 to January, 2015 and serum from 35 normal subjects were collected. The expression of CDC2 mRNA was evaluated using quantitative polymerase chain reaction (RT-PCR) and the relationship between CDC2 protein expression and clinical features of patients with osteosarcoma was analyzed. There was a significant difference in the expression levels of CDC2 between cancer (2.31±0.306) and paracancerous tissues (0.91±0.251) (P<0.05), and there was a difference in the expression of CDC2 in serum between patients (1.58±0.149) and the normal control group (0.67±0.136). Receiver operating characteristic (ROC) curve analysis indicated that CDC2 was of great value in the diagnosis of osteosarcoma. The expression of CDC2 was closely related to the tumor diameter (P<0.05), World Health Organization classification (P<0.05) and KPS score (P<0.05). However, there was no significant association between the expression of CDC2 and factors including age and sex (both P>0.05). The high expression of CDC2 was closely related to the lower survival rate in patients with osteosarcoma (P<0.05). The increase of the tumor-node-metastasis (TNM) staging of osteosarcoma and the high expression of CDC2 are the risk factors affecting the prognosis of osteosarcoma patients (P<0.05), and Cox regression analysis showed that the expression level of CDC2 was a risk factor affecting the prognosis of osteosarcoma patients (P<0.05). The results indicate that CDC2 is highly expressed in osteosarcoma and may be a biomarker to predict the occurrence, development and prognosis of osteosarcoma.

Expression level of  gene in osteosarcoma and its clinical significance.

Diabetes mellitus (DM) is a potential etiology of disc degeneration. N-cadherin (N-CDH) helps maintain the cell viability, cell phenotype and matrix biosynthesis of nucleus pulposus (NP) cells. Here, we mainly aimed to investigate whether N-CDH can attenuate high glucose-induced NP cell senescence and its potential mechanism.

N-Cadherin Attenuates High Glucose-Induced Nucleus Pulposus Cell Senescence Through Regulation of the ROS/NF-κB Pathway.

To compare clinical results of Sanders II-IV fractures of calcaneus treated by self-setting calcium phosphate cement and allograft with locking reconstruction bone plate internal fixation.

[Case-control study on self-setting calcium phosphate cement and allograft for Sanders II-IV fractures of calcaneus].

Long non‑coding (lnc)RNA sprouty receptor tyrosine kinase signalling antagonist 4‑intronic transcript 1 (SPRY4‑IT1) has been demonstrated to serve a critical role in the tumorigenesis of osteosarcoma (OS); however, the specific underlying mechanism remains unclear. The aim of the present study was to examine the interactions between SPRY4‑IT1 and its downstream effectors, to determine if any of the interactions contributed to SPRY4‑IT1‑mediated proliferation, migration and invasion in cancer cells. A signalling cascade which involved SPRY4‑IT1, miR‑101 and zinc finger E‑box‑binding homeoboxes (ZEBs) was examined in the present study. Intracellular SPRY4‑IT1 and miR‑101 expression levels were altered through transfection to assess their effect on proliferation, cell cycle progression, survival, migration and invasion. A dual‑luciferase assay was utilized to determine the association between SPRY4‑IT1/miR‑101 and ZEBs/miR‑101 and nude mouse xenograft experiments were performed to determine the effect of SPRY4‑IT1 in vivo. The results indicated that the SPRY4‑IT1 levels were negatively associated with miR‑101 expression levels in OS cells, an association which was not observed in the normal osteoblast cells. SPRY4‑IT1 knockdown or miR‑101 overexpression reduced proliferation, cell cycle progression, survival, migration and invasion of MG‑63 and U2OS cells. SPRY4‑IT1 knockdown was accompanied by increased expression of miR‑101 and E‑cadherin levels, as well as decreased expression levels of ZEB1/2 and other epithelial‑mesenchymal transition‑associated proteins. Simultaneous knockdown of SPRY4‑IT1 and inhibition of miR‑101 partially reversed the anti‑tumour effects of SPRY4‑IT1 inhibition in vitro. Consistent with these findings, short hairpin RNA targeting SPRY4‑IT1 also hindered xenograft tumour growth and altered the levels of miR‑101, ZEB1/2 and E‑cadherin in vivo. Dual‑luciferase reporter assays demonstrated that SPRY4‑IT1 may have regulated the expression of ZEB1 and ZEB2 by sponging miR‑101. In conclusion, SPRY4‑IT1 inhibition increased miR‑101 levels, resulting in downregulation of ZEB1/2 expression and thus exerting anti‑tumour effects in OS.

LncRNA SPRY4‑IT1 promotes progression of osteosarcoma by regulating ZEB1 and ZEB2 expression through sponging of miR‑101 activity.

Ankylosing spondylitis is a progressive, disabling joint disease that affects millions worldwide. Given its unclear etiology, studies of ankylosing spondylitis relied heavily on drug-induced or transgenic rodent models which retain only partial clinical features. There is obviously a lack of a useful disease model to conduct comprehensive mechanistic studies.

A new and spontaneous animal model for ankylosing spondylitis is found in cynomolgus monkeys.

A sensitive and reliable LC-MS/MS method is established and validated to determine the concentration of celecoxib, in the serum of cynomolgus monkey, using celecoxib-D7 as an internal standard. The pharmacokinetic process was investigated after giving Celebrex, celecoxib nanoparticles (CXB-NPs) and hyaluronic acid celecoxib nanoparticles (HA-CXB-NPs) by intragastric (i.g.) administration. Chromatographic separation was performed with a C column (2.1 × 100 mm, 2.6 μm) at 40°C with a mobile phase of 2‰ HCOOH in water and acetonitrile. The mass spectral acquisition was then performed in the multiple reaction monitoring mode, with negative ESI ion at m/z 380.0 → 316.0 and m/z 387.1 → 323.1 for celecoxib and celecoxib-D7, respectively. Good linearity was observed over the concentration range from 3 to 2,000 ng/ml (R  = 0.9954). The intra- and inter-day precision and accuracy, matrix effect and extraction recovery, as well as stability, all met the determination requirements of biological samples. The pharmacokinetic parameters of Celebrex, CXB-NPs and HA-CXB-NPs were determined as: area under the curve, 1,855.98 ± 346.59, 1,908.00 ± 1,130.24 and 2,164.48 ± 657.47 h·ng/ml; peak concentration, 261.08 ± 113.26, 261.12 ± 94.67 and 263.34 ± 151.78 μg/L; time to peak concentration, 2.00 ± 1.22, 4.00 ± 0.00 and 3.60 ± 0.89 h; half-life, 4.39 ± 1.26, 2.33 ± 0.94 and 4.92 ± 3.13 h; relative bioavailability, 102.80 ± 49.62 and 116.63 ± 25.55%. The validated method was successfully applied to the pharmacokinetic study of celecoxib in cynomolgus monkey, after i.g. administration. The preparation of the nanoparticles of celecoxib and the modification of hyaluronic acid on the surface of nanoparticles could improve the bioavailability and prolong the circulation of celecoxib in vivo, which could lay the foundation for further development of celecoxib nanoparticles.

The delivery of nanoparticles improves the pharmacokinetic properties of celecoxib to open a therapeutic window for oral administration of insoluble drugs.

Gang Hou

Department of Orthopedics

The Third Affiliated Hospital of Sun Yat-sen University

Ameliorating Osteoarthritis in Mice Using Silver Nanoparticles