construction-evaluation-murine-calvarial-osteolysis-model-exposure-to

Construction and Evaluation of a Murine Calvarial Osteolysis Model by Exposure to CoCrMo Particles in Aseptic Loosening

Wear particle-induced osteolysis is a major cause of aseptic loosening in arthroplasty failure, but the underlying mechanism remains unclear. Due to long ...

Nanjing University

Cancer treatment-related bone loss has become growing problematic, especially in breast and prostate cancer treated with hormone/endocrine therapy, chemotherapy and radiotherapy. However, bone loss caused by targeted therapy in cancer patients is largely unknown yet. In present study, a kinase inhibitors screen was applied for MC3T3-E1, a murine osteoprogenitor cell line, and seven kinase inhibitors (GSK1838705A, PF-04691502, Dasatinib, Masitinib, GDC-0941, XL880 and Everolimus) were found to suppress the cell viability with dose- and time-dependent manner. The most interesting is that many kinase inhibitors (such as lapatinib, erlotinib and sunitinib) can promote MC3T3-E1 cell proliferation at 0.01 μM. 4 out of 7 inhibitors were selected to perform the functional study and found that they lead to cell cycle dysregulation, treatments of PF-04691502 (AKT inhibitor), Dasatinib (Src inhibitor) and Everolimus (mTOR inhibitor) lead to G1 arrest of MC3T3-E1 cells via downregulation of cyclin D1 and p-AKT, whereas XL880 (MET and VEGFR inhibitor) treatment results in increase of sub-G1 and G2/M phase by upregulation of p53 protein. Our work provides important indications for the comprehensive care of cancer patients treated with some targeted drugs.

Systematic screen with kinases inhibitors reveals kinases play distinct roles in growth of osteoprogenitor cells.

Since the outbreak of pandemics, influenza has caused extensive attention in the field of public health. It is actually hard to distinguish what is the most effective method to control the influenza transmission within airport terminal. The purpose of this study was to quantitatively evaluate the influences of passenger source, immunity difference and social relation structure on the influenza transmission in terminal.

Influences on influenza transmission within terminal based on hierarchical structure of personal contact network.

Hidden blood loss typically occurs following total hip arthroplasty (THA) and total knee arthroplasty (TKA) and is thought to be related to free fatty acid (FFA). To study the effect of linoleic acid on red blood cells and to examine the pathogenesis of hidden blood loss in vivo, we generated an animal model by injecting linoleic acid into the tail veins of rats. We collected blood samples and determined red blood cell count (RBC) and levels of hemoglobin (Hb), as well as the oxidation and reducing agents in the blood, including glutathione peroxidase (GSH-PX), total superoxide dismutase (T-SOD), hydrogen peroxide (H2O2), and ferryl hemoglobin (Fe4+=O2-), which is generated by the oxidation of Hb. Hidden blood loss occurred when linoleic acid was administered at a concentration of 60 mmol/L; RBC and Hb levels were significantly reduced by 24 h post-injection. This was followed by erythrocyte deformation, reduced activity of GSH-PX and T-SOD, and decreased levels of H2O2. This was accompanied by an increase in ferryl species, which likely contributes to oxidative stress in vivo. Our findings suggest that linoleic acid enhances acute red blood cell injury. Hb and RBC began to increase by 72 h, potentially resulting from linoleic acid metabolism. Thus, elevated levels of linoleic acid in the blood cause acute oxidative damage to red blood cells, eventually leading to partial acute anemia. These findings highlight the pathophysiology underlying hidden blood loss.

Linoleic acid induces red blood cells and hemoglobin damage via oxidative mechanism.

A small-sized UAV (NH-UAV) airborne system with two gamma spectrometers (LaBr3 detector and HPGe detector) was developed to monitor activity concentration in serious nuclear accidents, such as the Fukushima nuclear accident. The efficiency calibration and determination of minimum detectable activity concentration (MDAC) of the specific system were studied by MC simulations at different flight altitudes, different horizontal distances from the detection position to the source term center and different source term sizes. Both air and ground radiation were considered in the models. The results obtained may provide instructive suggestions for in-situ radioactivity measurements of NH-UAV.

Efficiency calibration and minimum detectable activity concentration of a real-time UAV airborne sensor system with two gamma spectrometers.

Peri-prosthetic osteolysis and the consequent aseptic loosening constitute the most common reason for total joint arthroplasty failure and surgical revision. Although numerous studies suggest that pro-inflammatory cytokines induced by wear particles is involved in the pathological process of aseptic loosening, the underlying mechanism linking wear particles to pro-inflammatory cytokines remains to be illustrated. In the present study, we investigated the effect of autophagy on TNF-α secretion induced by TiAl6V4 particles (TiPs) in macrophages and in a calvarial resorption animal model. Our study demonstrated that TiPs activated autophage in macrophages and particle-induced osteolysis animal models as well as periprosthetic membranes of patients with aseptic loosening. The autophagy inhibitor 3-MA (3-methyladenine) could dramatically reduce TiPs-induced TNF-α expression both in macrophages and in membranes from animal models. Furthermore, inhibition of autophagy with 3-MA ameliorated the severity of osteolysis in PIO animal models. Collectively, these results suggest that autophagy plays a key role in TiPs-induced osteolysis by promoting TNF-α expression and that blocking autophagy may represent a potential therapeutic approach for treating particle-induced peri-implant osteolysis.

Autophagy mediated TiAl₆V₄ particle-induced peri-implant osteolysis by promoting expression of TNF-α.

Rheumatoid arthritis (RA) is a chronic inflammatory disease which results in progressive destruction of the joint. In this study, we examined if the hydrogen could inhibit inflammation in a mouse model of collagen-induced arthritis (CIA) via oxidative stress on RA-FLSs. Moreover, to identify the mechanisms of action, we evaluated the effect of hydrogen on RA-FLSs development and the expression of pro-inflammatory cytokines and signaling pathways. Based on our result, Henriched medium can increase super oxide dismutase (SOD) level following HOtreatment and decrease 8-hydroxy-2'-deoxyguanosine (8-OHdG) level. Since HOtreatment activates MAPK, NF-κB and TGF-β1 in cells, our study suggested that Hcould inhibit HOactivated MAPK and NF-κB activation as well as TGF-β1 expression in treated cells. Taken together, our data suggested that Hcan directly neutralize OH and ONOOto reduce oxidative stress. Moreover, MAPK and NF-κB pathway also play roles in oxidative damage caused by HOin RA-FLSs. Hcan provide protection to cells against inflammation, which may be related to inhibition of the activation of MAPK and NF-κB.

Molecular hydrogen decelerates rheumatoid arthritis progression through inhibition of oxidative stress.

Hidden blood loss (HBL), commonly seen after total knee or hip arthroplasty, causes postoperative anemia even after reinfusion or blood transfusion based on the visible blood loss volume. Recent studies demonstrated that oxidative stress might be involved in HBL. However, whether the antioxidants proanthocyanidin (PA) or hydrogen water (HW) can ameliorate HBL remains poorly understood. The aim of this study was to evaluate the effects of PA and HW on HBL.

Antioxidants Attenuate Oxidative Stress-Induced Hidden Blood Loss in Rats.

Background: To compare the risk of type 2 diabetes (T2DM) between patients with and without chronic osteomyelitis (COM), both in humans and in mice, and to explore risk factors in COM patients who developed T2DM. Methods: One hundred seven patients with COM and 114 patients without COM were consecutively enrolled and retrospectively analysed. Clinical data concerning the time to develop diabetes, glucose metabolism, lipid metabolism, inflammatory factors, mental health and frequency of specialist visits were collected. A mouse model of osteomyelitis was used to verify the presence of impaired glucose metabolism and depression. All data were processed by SPSS. Results: The incidence of T2DM was 2.37-fold higher in patients with COM than in those without. In COM patients, subjects with T2DM (DDM) had higher BMI, less exercise and more frequent visits to specialists than those without (Con). Glucose and lipid metabolism were worse in patients with DDM. Patients with DDM had higher levels of white blood cells (12.9±2.1×109/L vs. 11.7±2.2×109/L, p=0.027), CRP (28.4±4.5 mg/L vs. 22.0±4.8 mg/L, p<0.001), TNF-α (13.5±5.0 pg/mL vs. 9.4±2.6 pg/mL, p= 0.003) and IL-6 (12.9±3.2 pg/mL vs. 9.2±2.7 pg/mL, p<0.001). Significantly increased fasting blood glucose concentrations and impairment of oral glucose tolerance tests were also observed in mice modelling osteomyelitis, which were accompanied by elevated TNF-α and IL-6 levels. Furthermore, the proportion of depression (63.2% vs. 35.2%, p=0.003) and severe anxiety (31.6% vs. 9.1%, p=0.002) were significantly higher in the DDM group. Osteomyelitis mice showed obvious depressive-like behaviours. The levels of TNF-α, IL-6, CRP, BMI, and LDL; lack of exercise; SAS; HAQ; and SF36 assessment were risk factors for the development of T2DM in COM patients. Conclusions: Chronic osteomyelitis increased the incidence of T2DM in both humans and mice. Inflammation, mental illness and lack of exercise were risk factors for the occurrence of T2DM in osteomyelitis. Comprehensive consideration of patient history, including metabolism and mental health, is needed in planning future treatment.

Chronic Osteomyelitis Increases the Incidence of Type 2 Diabetes in Humans and Mice.

To compare the salvage rate and complication between internal fixation and external fixation in patients with small bone defects caused by chronic infectious osteomyelitis debridement.

Comparison of Monolateral External Fixation and Internal Fixation for Skeletal Stabilisation in the Management of Small Tibial Bone Defects following Successful Treatment of Chronic Osteomyelitis.

Article	Year
Systematic screen with kinases inhibitors reveals kinases play distinct roles in growth of osteoprogenitor cells. International journal of clinical and experimental pathology\| PubMed ID: 24133586	2013
Influences on influenza transmission within terminal based on hierarchical structure of personal contact network. BMC public health\| PubMed ID: 25849344	2015
Linoleic acid induces red blood cells and hemoglobin damage via oxidative mechanism. International journal of clinical and experimental pathology\| PubMed ID: 26191198	2015
Efficiency calibration and minimum detectable activity concentration of a real-time UAV airborne sensor system with two gamma spectrometers. Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine\| PubMed ID: 26773821	2016
Autophagy mediated TiAl₆V₄ particle-induced peri-implant osteolysis by promoting expression of TNF-α. Biochemical and biophysical research communications\| PubMed ID: 26996127	2016
Molecular hydrogen decelerates rheumatoid arthritis progression through inhibition of oxidative stress. American journal of translational research\| PubMed ID: 27830032	2016
Antioxidants Attenuate Oxidative Stress-Induced Hidden Blood Loss in Rats. Turkish journal of haematology : official journal of Turkish Society of Haematology\| PubMed ID: 28270376	2017
Chronic Osteomyelitis Increases the Incidence of Type 2 Diabetes in Humans and Mice. International journal of biological sciences\| PubMed ID: 29104510	2017
Comparison of Monolateral External Fixation and Internal Fixation for Skeletal Stabilisation in the Management of Small Tibial Bone Defects following Successful Treatment of Chronic Osteomye... BioMed research international\| PubMed ID: 29333448	2017

Jia Meng

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