Is the traction table necessary to treat femoral fractures with intramedullary nailing? A meta-analysis.

BACKGROUND: The traction table is generally used in femoral intramedullary nailing surgery. Recently, some published studies have shown that the same or better treatment effects can be gotten without a traction table. It remains no consensus on this issue. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was applied in this study. We searched PubMed, Embase, Web of Science, and Cochrane Library databases for eligible studies. The random-effect model was used to calculate the standardized mean difference (SMD) and risk ratios with 95% CIs. Trial sequential analysis (TSA) was performed to verify the results. RESULTS: The pooled estimates of seven studies, including 266 cases each in the manual traction group and traction table group, indicated that manual traction could shorten operative time [SMD, - 0.77; 95% CI (- 0.98, - 0.55); P < 0.00001] and preoperative set-up time [SMD, - 2.37; 95% CI (- 3.90, - 0.84); P = 0.002], but it would not reduce intraoperative blood loss volume and fluoroscopy time. No statistical difference was found in their fracture healing time, postoperative Harris scores, and malunion rate. The use of a Traction repositor could reduce the set-up time [SMD, - 2.48; 95% CI (- 4.91, - 0.05); P < 0.00001]. CONCLUSIONS: Compared with manual traction, the traction table in femoral intramedullary nailing surgery lengthened operative time and preoperative set-up time. At the same time, it did not show significant advantages in reducing blood loss volume and fluoroscopy time, or improving prognosis. In clinical practice, the optimal surgical plan must be made on a case-by-case basis to avoid unnecessary traction table use.

Experimental and theoretical studies on the extraction behavior of Cf(iii) by NTAamide(C8) ligand and the separation of Cf(iii)/Cm(iii).

In this work we studied the extraction behaviors of Cf(iii) by NTAamide (N,N,N',N',N'',N''-hexaocactyl-nitrilotriacetamide, C8) in nitric acid medium. Influencing factors such as contact time, concentration of NTAamide(C8), HNO3 and NO3 - as well as temperature were considered. The slope analysis showed that Cf(iii) should be coordinated in the form of neutral molecules, and the extraction complex should be Cf(NO3)3·2L (L = NTAamide(C8)), which can achieve better extraction effect under the low acidity condition. When the concentration of HNO3 was 0.1 mol L-1, the separation factor (SFCf/Cm) was 3.34. The extractant has application prospect to differentiate the trivalent Cf(iii) and Cm(iii) when the concentration of nitric acid is low. On the other hand, density functional theory (DFT) calculations were conducted to explore the coordination mechanism of NTAamide(C8) ligands with Cf/Cm cations. The NTAamide(C8) complexes of Cf(iii)/Cm(iii) have similar geometric structures, and An(iii) is more likely to form a complex with 1 : 2 stoichiometry (metal ion/ligands). In addition, bonding property and thermodynamics analyses showed that NTAamide(C8) ligands had stronger coordination ability with Cf(iii) over Cm(iii). Our work provides meaningful information with regard to the in-group separation of An(iii) in practical systems.

7,8-Dihydroxyflavone alleviates cardiac fibrosis by restoring circadian signals via downregulating Bmal1/Akt pathway.

Brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) pathway is a therapeutic target in cardiac diseases. A BDNF mimetic, 7,8-dihydroxyflavone (7,8-DHF), is emerging as a protective agent in cardiomyocytes; however, its potential role in cardiac fibroblasts (CFs) and fibrosis remains unknown. Thus, we aimed to explore the effects of 7,8-DHF on cardiac fibrosis and the possible mechanisms. Myocardial ischemia (MI) and transforming growth factor-ß1 (TGF-ß1) were used to establish models of cardiac fibrosis. Hematoxylin & eosin and Masson's trichrome stains were used for histological analysis and determination of collagen content in mouse myocardium. Cell viability kit, EdU (5-ethynyl-2'-deoxyuridine) assay and immunofluorescent stain were employed to examine the effects of 7,8-DHF on the proliferation and collagen production of CFs. The levels of collagen I, α-smooth muscle actin (α-SMA), TGF-ß1, Smad2/3, and Akt as well as circadian rhythm-related signals including brain and muscle Arnt-like protein 1 (Bmal1), period 2 (Per2), and cryptochrome 2 (Cry2) were analyzed. Treatment with 7,8-DHF markedly alleviated cardiac fibrosis in MI mice. It inhibited the activity of CFs accompanied by decreasing number of EdU-positive cells and downregulation of collagen I, α-SMA, TGF-ß1, and phosphorylation of Smad2/3. 7,8-DHF significantly restored the dysregulation of Bmal1, Per2, and Cry2, but inhibited the overactive Akt. Further, inhibition of Bmal1 by SR9009 effectively attenuated CFs proliferation and collagen production of CFs. In summary, these findings indicate that 7,8-DHF attenuates cardiac fibrosis and regulates circadian rhythmic signals, at least partly, by inhibiting Bmal1/Akt pathway, which may provide new insights into therapeutic cardiac remodeling.

Repurposing nitazoxanide as a novel anti-atherosclerotic drug based on mitochondrial uncoupling mechanisms.

BACKGROUND AND PURPOSE: The anthelmintic drug nitazoxanide has a mitochondrial uncoupling effect. Mitochondrial uncouplers have been proven to inhibit smooth muscle cell proliferation and migration, inhibit NLRP3 inflammasome activation of macrophages and improve dyslipidaemia. Therefore, we aimed to demonstrate that nitazoxanide would protect against atherosclerosis. EXPERIMENTAL APPROACH: The mitochondrial oxygen consumption of cells was measured by using the high-resolution respirometry system, Oxygraph-2K. The proliferation and migration of A10 cells were measured by using Edu immunofluorescence staining, wound-induced migration and the Boyden chamber assay. Protein levels were measured by using the western blot technique. ApoE (-/-) mice were fed with a Western diet to establish an atherosclerotic model in vivo. KEY RESULTS: The in vitro experiments showed that nitazoxanide and tizoxanide had a mitochondrial uncoupling effect and activated cellular AMPK. Nitazoxanide and tizoxanide inhibited serum- and PDGF-induced proliferation and migration of A10 cells. Nitazoxanide and tizoxanide inhibited NLRP3 inflammasome activation in RAW264.7 macrophages, the mechanism by which involved the AMPK/IκBα/NF-κB pathway. Nitazoxanide and tizoxanide also induced autophagy in A10 cells and RAW264.7 macrophages. The in vivo experiments demonstrated that oral administration of nitazoxanide reduced the increase in serum IL-1ß and IL-6 levels and suppressed atherosclerosis in Western diet-fed ApoE (-/-) mice. CONCLUSION AND IMPLICATIONS: Nitazoxanide inhibits the formation of atherosclerotic plaques in ApoE (-/-) mice fed on a Western diet. In view of nitazoxanide being an antiprotozoal drug already approved by the FDA, we propose it as a novel anti-atherosclerotic drug with clinical translational potential.

Small-molecule 7,8-dihydroxyflavone counteracts compensated and decompensated cardiac hypertrophy via AMPK activation.

BACKGROUND: Pathological cardiac hypertrophy is a compensated response to various stimuli and is considered a key risk factor for heart failure. 7,8-Dihydroxyflavone (7,8-DHF) is a flavonoid derivative that acts as a small-molecule brain-derived neurotrophic factor mimetic. The present study aimed to explore the potential role of 7,8-DHF in cardiac hypertrophy. METHODS: Kunming mice and H9c2 cells were exposed to transverse aortic constriction or isoproterenol (ISO) with or without 7,8-DHF, respectively. F-actin staining was performed to calculate the cell area. Transcriptional levels of hypertrophic markers, including ANP, BNP, and ß-MHC, were detected. Echocardiography, hematoxylin-eosin staining, and transmission electron microscopy were used to examine the cardiac function, histology, and ultrastructure of ventricles. Protein levels of mitochondria-related factors, such as adenosine monophosphate-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), were detected. RESULTS: 7,8-DHF inhibited compensated and decompensated cardiac hypertrophy, diminished the cross-sectional area, and alleviated the mitochondrial disorders of cardiomyocytes. Meanwhile, 7,8-DHF reduced the cell size and repressed the mRNA levels of the hypertrophic markers of ISO-treated cardiomyocytes. In addition, 7,8-DHF activated AMPK and PGC-1α signals without affecting the protein levels of mitochondrial dynamics-related molecules. The effects of 7,8-DHF were eliminanted by Compound C, an AMPK inhibitor. CONCLUSIONS: These findings suggest that 7,8-DHF inhibited cardiac hypertrophy and mitochondrial dysfunction by activating AMPK signaling, providing a potential agent for the treatment of pathological cardiac hypertrophy.

Realizing high-performance and low-cost lithium-ion capacitor by regulating kinetic matching between ternary nickel cobalt phosphate microspheres anode with ultralong-life and super-rate performance and watermelon peel biomass-derived carbon cathode.

Lithium-ion capacitors (LICs) are emerging as one of the most advanced energy storage devices by combining the virtues of both supercapacitors (SCs) and lithium-ion batteries (LIBs). However, the kinetic and capacity mismatch between anode and cathode is the main obstacle to wide applications of LICs. Therefore, the effective strategy of constructing a high-performance LIC is to improve the rate and cycle performance of the anode and the specific capacity of the cathode. Herein, the nickel cobalt phosphate (NiCoP) microspheres anode is demonstrated with robust structural integrity, high electrical conductivity, and fast kinetic feature. Simultaneously, the watermelon-peel biomass-derived carbon (WPBC) cathode is demonstrated a sustainable synthesis strategy with high specific capacity. As expected, the NiCoP exhibits high specific capacities (567 mAh g-1 at 0.1 A g-1), superior rate performance (300 mAh g-1 at 1A g-1), and excellent cycle stability (58 mAh g-1 at 5 A g-1 after 15,000 cycles). The WPBC possesses a high specific surface area (SSA) of 3303.6 m2 g-1 and a high specific capacity of 226 mAh g-1 at 0.1 A g-1. Encouragingly, the NiCoP//WPBC-6 LIC device can deliver high energy density (ED) of 127.4 ± 3.3 and 67 ± 3.8Wh kg-1 at power density (PD) of 190 and 18240 W kg-1 (76.4% capacity retention after 7000 cycles), respectively.

Crystal Phase-Controlled Synthesis of the CoP@Co2P Heterostructure with 3D Nanowire Networks for High-Performance Li-Ion Capacitor Applications.

The paramount focus in the construction of lithium-ion capacitors (LICs) is the development of anode materials with high reversible capacity and fast kinetics to overcome the mismatch of kinetics and capacity between the anode and cathode. Herein, a strategy is presented for the controllable synthesis of cobalt-based phosphides with various morphologies by adjusting the time of the phosphidation process, including 3D hierarchical needle-stacked diabolo-shaped CoP nanorods, 3D hierarchical stick-stacked diabolo-shaped Co2P nanorods, and 3D hierarchical heterostructure CoP@Co2P nanorods. 3D hierarchical nanostructures and a highly conductive project to accommodate volume changes are rational designs to achieve a robust construction, effective electron-ion transportation, and rapid kinetics characteristics, thus leading to excellent cycling stability and rate performance. Owing to these merits, the 3D hierarchical CoP, Co2P, and CoP@Co2P nanorods demonstrate prominent specific capacities of 573, 609, and 621 mA h g-1 at 0.1 A g-1 over 300 cycles, respectively. In addition, a high-performance CoP@Co2P//AC LIC is successfully constructed, which can achieve high energy densities of 166.2 and 36 W h kg-1 at power densities of 175 and 17524 W kg-1 (83.7% capacity retention after 12000 cycles). Therefore, the controllable synthesis of various simultaneously constructed crystalline phases and morphologies can be used to fabricate other advanced energy storage devices.

Chemical mitochondrial uncouplers share common inhibitory effect on NLRP3 inflammasome activation through inhibiting NFκB nuclear translocation.

Activation of NLRP3 inflammasome is implicated in varieties of pathologies, the aim of the present study is to characterize the effect and mechanism of mitochondrial uncouplers on NLRP3 inflammasome activation by using three types of uncouplers, niclosamide, CCCP and BAM15. Niclosamide, CCCP and BAM15 inhibited LPS plus ATP-induced increases of NLRP3 protein and IL-1ß mRNA levels in RAW264.7 macrophages and THP-1 derived macrophages. Niclosamide, CCCP and BAM15 inhibited LPS plus ATP-induced increase of NFκB (P65) phosphorylation, and inhibited NFκB (P65) nuclear translocation in RAW264.7 macrophages. Niclosamide and BAM15 inhibited LPS-induced increase of IκBα phosphorylation in RAW264.7 macrophages, and the inhibitory effect was dependent on increased intracellular [Ca2+]i; however, CCCP showed no significant effect on IκBα phosphorylation in RAW264.7 macrophages stimulated with LPS. In conclusion, chemical mitochondrial uncouplers niclosamide, CCCP and BAM15 share common inhibitory effect on NLRP3 inflammasome activation through inhibiting NFκB nuclear translocation.

Effects of Gentiana delavayi Flower Extract on APP Processing in APP/PS1 CHO Cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Gentiana delavayi Franch. (Gentianaceae) as an ethnomedicinal plant contains a variety of effective active ingredients and exhibits diverse pharmacological actions, such as hepatoprotective, anti-inflammatory and central nervous system effects. In this study we investigated the influence of G. delavayi flower extract on amyloid precursor protein (APP) processing at molecular and cellular levels. APP/PS1 Chinese hamster ovary (CHO) cells were treated with chloroform extract of G. delavayi flower in different concentrations for 24 h. Concentrations of amyloid ß (Aß) 40 and Aß42 in the cell supernatant and activity of ß-site amyloid precursor protein cleaving enzyme 1 (BACE1), BACE2, and cathepsin D were determined. The expression of APP and neprilysin (NEP) within the cell were further determined. Compared with the control group, the levels of Aß40 and Aß42 declined notably and the activity of BACE1 was inhibited significantly in the APP/PS1 CHO cells after treatment with the chloroform extract of G. delavayi flower. Although the activities of BACE2 and cathepsin D were not changed, the expression of Aß degrading enzyme NEP increased remarkably. Our experiments have clearly showed that the chloroform extract of G. delavayi flower inhibits the generation of ß-amyloid by specifically inhibiting ß-secretase and increases the expression of NEP which fastens the degradation of Aß, exhibiting the effect of decreasing Aß accumulation in APP/PS1 CHO cells. These results suggest that the active components from the chloroform extract of G. delavayi flower have a further prospect to be developed as potential anti-Aß drug.

Rice defense responses are induced upon leaf rolling by an insect herbivore.

BACKGROUND: Plant defense against herbivores begins with perception. The earlier plant detects the harm, the greater plant will benefit in its arm race with the herbivore. Before feeding, the larvae of the rice pest Cnaphalocrocis medinalis, initially spin silk and fold up a leaf. Rice can detect and protect itself against C. medinalis feeding. However, whether rice could perceive C. medinalis leaf rolling behavior is currently unknown. Here, we evaluated the role of leaf rolling by C. medinalis and artificial leaf rolling in rice plant defense and its indirect effect on two important C. medinalis parasitoids (Itoplectis naranyae and Apanteles sp.) through a combination of volatile profiling, gene-transcriptional and phytohormonal profiling. RESULTS: Natural leaf rolling by C. medinalis resulted in an increased attraction of I. naranyae when compared to the undamaged plant after 12 h. Volatile analysis revealed that six out of a total 22 components significantly increased in the headspace of C. medinalis rolled plant when compared to undamaged plant. Principal component analysis of these components revealed similarities in the headspace of undamaged plant and artificially rolled plant while the headspace volatiles of C. medinalis rolled plant deferred significantly. Leaf rolling and feeding by C. medinalis up-regulated the plant transcriptome and a series of jasmonic acid (JA) and salicylic acid (SA) related genes. While feeding significantly increased JA level after 12 to 36 h, rolling significantly increased SA level after 2 to 12 h. Compared to artificial rolling, natural rolling significantly increased JA level after 36 h and SA level after 2 and 12 h. CONCLUSIONS: Our findings suggest that natural leaf rolling by C. medinalis can be perceived by rice plant. The detection of this behavior may serve as an early warning signal in favor of the rice plant defenses against C. medinalis.

Body mass index and the risk of cancer in women compared with men: a meta-analysis of prospective cohort studies.

Studies investigating the association between BMI and the risk of the common cancers in men or women have reported inconsistent results. We searched the PubMed, Embase, and Cochrane Library electronic databases for relevant articles published until April 2015. Overall, we analyzed 128 datasets (51 articles), including 154 939 incident cancer cases. The pooled relative risk ratio (RRR) (female to male) showed that the relative risk of overweight associated with colorectal [RRR: 0.91; 95% confidence interval (CI): 0.85-0.97] or rectal cancer (RRR: 0.94; 95% CI: 0.88-0.99) was significantly lower in women than in men. However, the relative risk of overweight associated with lung (RRR: 1.14; 95% CI: 1.06-1.22) or kidney cancer (RRR: 1.15; 95% CI: 1.05-1.26) was significantly higher in women than in men. Furthermore, the relative risk of obesity associated with liver (RRR: 0.71; 95% CI: 0.51-0.99), colorectal (RRR: 0.83; 95% CI: 0.75-0.93), colon (RRR: 0.73; 95% CI: 0.68-0.0.78), rectal (RRR: 0.84; 95% CI: 0.76-0.92), and kidney cancer (RRR: 1.20; 95% CI: 1.06-1.37) differed significantly between women and men. Finally, the relative risk of underweight associated with gastric (RRR: 0.83; 95% CI: 0.70-0.97), liver (RRR: 0.83; 95% CI: 0.71-0.97), and gallbladder cancer (RRR: 1.25; 95% CI: 1.04-1.49) differed significantly according to sex. In conclusion, our study showed that the association between BMI and the risk of several cancers was significantly different between the sexes. For some cancer types, the sex difference was affected by country, sample size, follow-up duration, and study quality.

Tris(5,6-dimethyl-1H-benzimidazole-κN(3))(pyridine-2,6-dicarboxyl-ato-κ(3)O(2),N,O(6))nickel(II).

The title mononuclear complex, [Ni(C(7)H(3)NO(4))(C(9)H(10)N(2))(3)], shows a central Ni(II) atom which is coordinated by two carboxyl-ate O atoms and the N atom from a pyridine-2,6-dicarboxyl-ate ligand and by three N atoms from different 5,6-dimethyl-1H--benzimidazole ligands in a distorted octa-hedral geometry. The crystal structure shows intermolecular N-H⋯O hydrogen bonds.

Tris(1H-benzimidazole-κN(3))(pyridine-2,6-dicarb-oxy-lato-κ(3)O(2),N,O(6))nickel(II).

In the title complex, [Ni(C(7)H(3)NO(4))(C(7)H(6)N(2))(3)], the Ni(II) ion is coordinated by two carboxyl-ate O atoms and the N atom from a pyridine-2,6-dicarboxyl-ate ligand and by three N atoms from three benzimidazole ligands to form a slightly distorted octa-hedral geometry. In the crystal, mol-ecules are linked by N-H⋯O hydrogen bonds to form a three-dimensional network.

The effect of aligned core-shell nanofibres delivering NGF on the promotion of sciatic nerve regeneration.

Recent bioengineering strategies for peripheral nerve regeneration have been focusing on the development of alternative treatments for nerve repair. In this study, we incorporated nerve growth factor (NGF) into aligned core-shell nanofibres by coaxial electrospinning, and reeled the scaffold into aligned fibrous nerve guidance conduits (NGCs) for nerve regeneration study. This aligned PLGA/NGF NGC combined physical guidance cues and biomolecular signals to closely mimic the native extracellular matrix (ECM). The effect of this aligned PLGA/NGF NGC on the promotion of nerve regeneration was evaluated in a 13-mm rat sciatic nerve defect using functional and morphological analysis. After 12 weeks implantation, the results of electrophysiological and muscle weight examination demonstrated that the functional recovery of the regenerated nerve in the PLGA/NGF NGC group was significantly better than that in the PLGA group, yet had no significant difference compared with the autograft group. The toluidine blue staining study showed that more nerve fibres were regenerated in the PLGA/NGF group, while the electron microscopy study indicated that the regenerated nerve in the PLGA/NGF group was more mature than that in the PLGA group. This study demonstrated that the aligned PLGA/NGF could greatly promote peripheral nerve regeneration and have a potential application in nerve regeneration.

Combination of arthrolysis by lateral and medial approaches and hinged external fixation in the treatment of stiff elbow.

BACKGROUND: Various methods are available to treat the stiff elbow. However, there is no consensus on which one is most useful. This study involves the effects of combination of arthrolysis by lateral and medial approaches and hinged external fixation in the treatment of stiff elbow. PATIENTS: We treated 12 patients with stiff elbows using a combination of arthrolysis by lateral and medial approaches and hinged external fixation. The arthrolysis was applied to the elbow for complete soft-tissue release, and the hinged external fixation mainly for rehabilitation and stability of the elbow after arthrolysis. With the help of the hinged external fixation, nonsurgical treatment including exercises was effectively performed to maintain the stability and the results of arthrolysis. Before surgery, the mean extension was -35 degrees and the mean flexion 70 degrees. One patient had a loss of 70 degrees in pronation. RESULTS: Satisfactory follow-up was given to 11 patients with the mean length of 15 month. The mean postoperative extension was -8 degrees whereas flexion 122 degrees. Two of 11 patients had a transient ulnar paresthesia and returned to normal after 8-month follow-up. The loss of pronation in one patient reduced to 30 degrees afterward. There were no complicating infections. All patients reported satisfactory effect. CONCLUSION: The combination of arthrolysis by lateral and medial approaches and hinged external fixation in the treatment of stiff elbow is safe and effective.

Aligned natural-synthetic polyblend nanofibers for peripheral nerve regeneration.

Peripheral nerve regeneration remains a significant clinical challenge to researchers. Progress in the design of tissue engineering scaffolds provides an alternative approach for neural regeneration. In this study aligned silk fibroin (SF) blended poly(L-lactic acid-co-ε-caprolactone) (P(LLA-CL)) nanofibrous scaffolds were fabricated by electrospinning methods and then reeled into aligned nerve guidance conduits (NGC) to promote nerve regeneration. The aligned SF/P(LLA-CL) NGC was used as a bridge implanted across a 10mm defect in the sciatic nerve of rats and the outcome in terms of of regenerated nerve at 4 and 8 weeks was evaluated by a combination of electrophysiological assessment and histological and immunohistological analysis, as well as electron microscopy. The electrophysiological examination showed that functional recovery of the regenerated nerve in the SF/P(LLA-CL) NGC group was superior to that in the P(LLA-CL) NGC group. The morphological analysis also indicated that the regenerated nerve in the SF/P(LLA-CL) NGC was more mature. All the results demonstrated that the aligned SF/P(LLA-CL) NGC promoted peripheral nerve regeneration significantly better in comparison with the aligned P(LLA-CL) NGC, thus suggesting a potential application in nerve regeneration.

Soluble P selectin in synovial fluid level is correlated with the radiographic severity of knee osteoarthritis.

BACKGROUND: Recent studies provide evidence that inflammation is a feature of the disease process in Osteoarthritis (OA). The clinical significance of P selectin (Ps) in OA has not been adequately studied and the association between Ps level and OA severity remains unknown. METHODS: We enrolled 120 knee OA subjects and 45 controls. All patients were scored for Kellgren-Lawrence grade (0-4). The Ps in serum and synovial fluid (SF) as well as serum C-reactive protein (CRP) levels were detected. RESULTS: The mean Ps level in OA subjects was markedly increased than that in controls. In OA patients, the SF Ps levels increased with the severity of KL scores and significantly correlated with severity of disease (r=0.546, P<0.001) and serum CRP level (r=0.488, P<0.001). However, the serum Ps level did not show a significant correlation with the severity of OA. CONCLUSION: The Ps levels in SF were significantly correlated with the severity of OA, suggesting that it may be used as a biomarker to evaluate the progression of OA.

Transforming growth factor-beta activated kinase 1 signaling pathways regulate TNF-alpha production by titanium alloy particles in RAW 264.7 cells.

Implant particles may induce inflammatory response by activating the nuclear factor kappaB (NFkappaB) and mitogen activated protein kinases (MAPK). Previous studies have shown that these signaling pathways are involved in the transforming growth factor-beta activated kinase 1 (TAK1) in signaling cascades induced by the receptor activator of NFkappaB ligand (RANKL) and tumor necrosis factor-alpha (TNF-alpha) as well as interleukin-1beta (IL-1beta). In this study, the roles of the TAK1 pathway in the production of the pro-inflammatory cytokine TNF-alpha in RAW 264.7 cells exposed to titanium alloy particles were investigated. Endogenous TAK1 was phosphorylated upon simulating RAW 264.7 cells by titanium alloy particles. The critical role for TAK1 in p38MAPK and NFkappaB activation was as well confirmed by the inhibition of p38MAPK and NFkappaB activity following 5Z-7-oxozeaenol, a selective inhibitor of TAK1. Furthermore, it was found that TNF-alpha was completely blocked by 5Z-7-oxozeaenol in RAW 264.7 cells. These results suggest that the TAK1-MAPK-NFkappaB signaling pathways may be a potential pharmacological target that can prevent instability for arthroplasty prosthesis.