Selenomethionine against titanium particle-induced osteolysis by regulating the ROS-dependent NLRP3 inflammasome activation via the ß-catenin signaling pathway.

Wear debris-induced osteolysis, especially titanium (Ti) particles-induced osteolysis, is the most common cause of arthroplasty failure with no effective therapy. Previous studies have suggested that inflammation and impaired osteogenesis are associated with Ti particles -induced osteolysis. Selenium (Se) is an essential trace element in the human body, which forms selenomethionine (Se-Met) in nature, and selenoproteins has strong anti-inflammatory and antioxidant stress effects. In this study, the effects of Se-Met on Ti particles-induced osteolysis were observed and the potential mechanism was explored. We found that exogenous Se-Met relieved osteolysis induced by Ti particles in two animal models and MC3T3-E1 cells. We found that the addition of Se-Met effectively inhibited Ti particle-induced inflammation by regulating reactive oxygen species-dependent (ROS-dependent) NOD-like receptor protein 3 (NLRP3) inflammasome activation. These therapeutic effects were abrogated in MC3T3-E1 cells that had received a ß-catenin antagonist, suggesting that Se-Met alleviates inflammatory osteolysis via the ß-catenin signaling pathway. Collectively, these findings indicated that Se-Met may serve as a potential therapeutic agent for treating Ti particle-induced osteolysis.

The role of wheat embryo globulin nutrients in improving cognitive dysfunction in AD rats.

Neuroinflammation and intestinal microbiota cause pathological progression of Alzheimer's disease (AD), leading to neurodegeneration and cognitive decline. This study investigates the effects of wheat embryo globulin nutrient (WEGN) on depression, neuroinflammation, and intestinal microbial disorder caused by AD and its protective mechanism on cognitive impairment. Results demonstrated that rats in the WEGN group have lower feed intake but higher body weight than those in the control group. Notably, rats in the WEGN group have a higher number of cross grids and uprights and a smaller amount of fecal particles than those in the control group. Biochemical examinations revealed that rats in the WEGN group had lower expression of interleukin-1ß, interleukin-6, and tumor necrosis factor α in hippocampus tissue and the expression of genes and proteins related to the TLR4/MyD88/NF-κB signaling pathway in AD rats was down-regulated compared to those in the control group. The 16S rRNA gene sequencing results demonstrated that WEGN treatment inhibits the increase of Erysipelotrichaceae, Erysipelatoclostridium, Erysipelotrichaceae, Corynebacterium, and Frisingicoccus, and the reduction of Lactobacillus in AD rats. WEGN has potential value as a practical food in alleviating neuroinflammation-related diseases such as AD.

In vitro dynamic digestion and anti-fatigue effects of wheat embryo albumin.

Wheat germ protein including wheat embryo albumin (WEA) demonstrates extensive biological activity. In vitro dynamic digestion of WEA was carried out under simulated gastrointestinal conditions. Anti-fatigue effects of WEA were evaluated using mice forced to swim. Results indicated that the digestibility of WEA decreased, antioxidant activity and the contents of aromatic amino acids (AAA) and hydrophobic amino acids (HAA) were significantly increased, and the ratio of essential amino acid (EAA) and non-essential amino acid (NEAA) were also changed during digestion. WEA significantly prolonged swimming time, reduced the accumulation of lactate dehydrogenase (LDH), blood urea nitrogen (BUN), and creatine kinase (CK). WEA also increased glycogen storage in liver and muscle. Meanwhile, WEA revealed antioxidant activity through enhancing the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) while decreasing the level of malondialdehyde (MDA). Notably, WEA enhanced the mRNA expression of mitochondrial biogenesis factors in the skeletal muscles of the mice. Therefore, WEA is suitable for preparation of energy foods with attractive anti-fatigue and health benefits.

Wheat embryo globulin nutrients ameliorate d-galactose and aluminum chloride-induced cognitive impairment in rats.

Wheat embryo globulin nutrient (WEGN), with wheat embryo globulin (WEG) as the main functional component, is a nutritional combination that specifically targets memory impairment. In this study, we explored the protective role of WEGN on Alzheimer's disease (AD)-triggered cognitive impairment, neuronal injury, oxidative stress, and acetylcholine system disorder. Specifically, we established an AD model via administration of d-galactose (d-gal) and Aluminum chloride (AlCl3) for 70 days, then on the 36th day, administered animals in the donepezil and WEGN (300, 600, and 900 mg/kg) groups with drugs by gavage for 35 days. Learning and memory ability of the treated rats was tested using the Morris water maze (MWM) and novel object recognition (NOR) test, while pathological changes and neuronal death in their hippocampus CA1 were detected via HE staining and Nissl staining. Moreover, we determined antioxidant enzymes by measuring levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in serum, cortex, and hippocampus, whereas changes in the acetylcholine system were determined by evaluating choline acetyltransferase (ChAT), and acetylcholinesterase (AChE) activities, as well as choline acetylcholine (Ach) content. Results revealed that rats in the WEGN group exhibited significantly lower escape latency, as well as a significantly higher number of targeted crossings and longer residence times in the target quadrant, relative to those in the model group. Notably, rats in the WEGN group spent more time exploring new objects and exhibited lower damage to their hippocampus neuron, had improved learning and memory activity, as well as reversed histological alterations, relative to those in the model group. Meanwhile, biochemical examinations revealed that rats in the WEGN group had significantly lower MDA levels and AChE activities, but significantly higher GSH, SOD, and ChAT activities, as well as Ach content, relative to those in the model group. Overall, these findings indicate that WEGN exerts protective effects on cognitive impairment, neuronal damage, oxidative stress, and choline function in AD rats treated by d-gal/AlCl3.

Correction to: Ghrelin Fights against Titanium Particle-Induced Inflammatory Osteolysis through Activation of ß-Catenin Signaling Pathway.

The original version of this article was published with incorrect Fig. 1B. The correct Fig. 1B is now presented in Fig. 1 shown at the next page.

Ghrelin Fights Against Titanium Particle-Induced Inflammatory Osteolysis Through Activation of ß-Catenin Signaling Pathway.

Aseptic loosening is a major complication of prosthetic joint surgery, in which exaggerated inflammation and impaired osteoblastogenesis are detected. Ghrelin is a recently discovered neuropeptide that is closely associated with inflammatory conditions and bone regeneration. Here, we report that titanium particles inhibited ghrelin expression in MC3T3-E1 cells. Furthermore, exogenous ghrelin effectively inhibited titanium particle-induced inflammation in vitro by interacting with its receptor GHSR1a; as an inhibitor of GHSR1a, Dlys repressed the function of ghrelin. Moreover, ghrelin attenuated the impairment of osteoblastogenesis and the exaggeration of osteolysis induced by titanium particles. Furthermore, the protective role of ghrelin in aseptic loosening might be associated with the Wnt/ß-catenin signaling pathway. Collectively, these findings suggest that ghrelin might be a potential therapeutic target for wear-debris-induced inflammation and osteolysis.

Regulatory effect of neuroglobin in the recovery of spinal cord injury.

OBJECTIVE: The present study was aimed to investigate the therapeutic potential of neuroglobin in the recovery of spinal cord injury. METHODS: The male albino Wistar strain rats were used as an experimental model, and adeno associated virus (AAV) was administered in the T12 section of spinal cord ten days prior to the injury. Basso Beattie Bresnahan (BBB) locomotor rating scale was used to determine the recovery of the hind limb during four weeks post-operation. Malondialdehyde (MDA), catalase and superoxide dismutase (SOD) were determined in the spinal cord tissues. Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay was carried out to determine the presence of apoptotic cells. Immunofluorescence analysis was carried out to determine the neuroglobin expression. Western blot analysis was carried out to determine the protein expressions of caspase-3, cytochrome c, bax and bcl-2 in the spinal cord tissues. RESULTS: Experimental results showed that rats were recovered from the spinal cord injury due to increased neuroglobin expression. Lipid peroxidation was reduced, whereas catalase and SOD activity were increased in the spinal cord tissues. Apoptosis and lesions were significantly reduced in the spinal cord tissues. Caspase-3, cytochrome c and bax levels were significantly reduced, whereas bcl-2 expression was reduced in the spinal cord tissues. CONCLUSION: Taking all these data together, it is suggested that the increased neuroglobin expression could improve the locomotor function.

Salvianolic Acid B Suppresses Inflammatory Mediator Levels by Downregulating NF-κB in a Rat Model of Rheumatoid Arthritis.

BACKGROUND Salvianolic acid B (SB) is a major active phyto-component of the plant Radix Salvia miltiorrhiza, which is traditionally used to treat joint pain and arthritis. The present study examined the anti-rheumatoid arthritis efficacy of SB on collagen-induced rheumatoid arthritis (CIA) in a rat model. MATERIAL AND METHODS Forty-eight rats were divided into 4 groups: Control rats treated with saline (Group I), rats subjected to CIA induction by intradermal injection of bovine collagen II type at the tail (Group II), and rats subjected to CIA and supplemented with either 20 or 40 mg/kg of SB for 28 days (group III or IV). RESULTS Paw swelling, edema, arthritis score, thymus and spleen indexes, and neutrophil infiltration were significantly decreased (p<0.01) by treatment with 20 or 40 mg/kg of SB. The levels of inflammatory cytokines (interleukin-1ß, -6, and -17, and TNF-α) and anti-collagen II-specific immunoglobulins (IgG1 and IgG2a) were markedly decreased (p<0.01), and those of antioxidant enzymes (SOD, CAT, and GSH) were significantly increased (p<0.01) in SB-treated rats. Administration with SB (20 or 40 mg/kg) resulted in lower phosphorylated IkB-a and NF-κB p65 protein levels and markedly downregulated IκB-a expression. Furthermore, CIA rats revealed the presence of highly diffused polymorphonuclear cells (PMNs) infiltration with eroded cartilage; however, these phenomena were considerably ameliorated by SB. CONCLUSIONS SB alleviates oxidative stress and inflammation in CIA rats, thus verifying its anti-rheumatoid arthritis property.

New insights on the MMP-13 regulatory network in the pathogenesis of early osteoarthritis.

Osteoarthritis (OA) is the most common joint disorder and affects approximately half of the aged population. Current treatments for OA are largely palliative until the articular cartilage has been deeply damaged and irreversible morphological changes appear. Thus, effective methods are needed for diagnosing and monitoring the progression of OA during its early stages when therapeutic drugs or biological agents are most likely to be effective. Various proteinases involved in articular cartilage degeneration in pre-OA conditions, which may represent the earliest reversible measurable changes, are considered diagnostic and therapeutic targets for early OA. Of these proteinases, matrix metalloproteinase 13 (MMP-13) has received the most attention, because it is a central node in the cartilage degradation network. In this review, we highlight the main MMP-13-related changes in OA chondrocytes, including alterations in the activity and expression level of MMP-13 by upstream regulatory factors, DNA methylation, various non-coding RNAs (ncRNAs), and autophagy. Because MMP-13 and its regulatory networks are suitable targets for the development of effective early treatment strategies for OA, we discuss the specific targets of MMP-13, including upstream regulatory proteins, DNA methylation, non-coding RNAs, and autophagy-related proteins of MMP-13, and their therapeutic potential to inhibit the development of OA. Moreover, the various entities mentioned in this review might be useful as early biomarkers and for personalized approaches to disease prevention and treatment by improving the phenotyping of early OA patients.

[Anterior cervical intervertebral space decompression under microscope for cervical spondylotic myelopathy in elderly patients].

OBJECTIVE: To investigate the clinical effects of anterior cervical intervertebral space decompression under microscope in treating cervical spondylotic myelopathy in elderly patients. METHODS: From June 2009 to March 2012, 43 patients with cervical spondylotic myelopathy were treated with anterior cervical intervertebral space decompression and intervertebral fusion under microscope. There were 26 males and 17 females, aged from 60 to 72 years old with an average of (64.9±3.7) years. Japanese Orthopaedic Association System (JOA) score was from 7 to 12 points with an average of (9.5±1.8) points before operation. The function of nerves was assessed before and after operation according to JOA. RESULTS: All patients were followed up from 10 to 18 months with an average of (14.7±1.6) months. Postoperative JOA score was (13.81±1.44) points (ranged, 10 to 16), had significantly higher than preoperative (P<0.01). According to the rate of the improved JOA score, 9 cases got excellent results, 26 good, 7 fair, 1 poor. CONCLUSION: Anterior cervical intervertebral space decompression under microscope for cervical spondylotic myelopathy in elderly patients is safe and effective.

Fractures of the posterior wall of the acetabulum: treatment using internal fixation of two parallel reconstruction plates.

OBJECTIVES: Our aim was to evaluate the efficacy of the treatment method using internal fixation of parallel reconstruction plates for the posterior wall of the acetabulum fractures. DESIGN: Randomised, prospective. SETTING: Level I trauma centre. PATIENTS/PARTICIPANTS: 57 patients with posterior wall fractures of the acetabulum in our department from 2007 to 2010 were treated operatively using this technique. INTERVENTION: internal fixation of two parallel reconstruction plates was used in this study. One of the plates was near the border of acetabulum. The other was parallel to the former one and was located to stress concentrated area. MAIN OUTCOME MEASUREMENTS: The clinical outcome was evaluated using the clinical grading system and radiological outcome was evaluated according to the criteria described by Matta. In addition, complications were researched in this study. RESULTS: The percentages of the clinical excellent-to-good and fair-to-poor results were 93.0% and 7%, respectively. We found that clinical outcome had no correlation with age, operation time from injury to operation, nor had correlation with hip dislocation, comminuted fracture condition and marginal compression fracture. Anatomical reduction was significantly correlated with excellent-to-good clinical outcome. Necrosis of the femoral head and heterotopic ossification were prone to decline the outcome of acetabular fractures despite good fracture reduction. CONCLUSIONS: the internal fixation of two parallel reconstruction plates facilitated rigid fixation and avoided fracture fragment injury, was an effective and reliable alternative method to treat fractures of the posterior wall of the acetabulum.

Dynamic cervical plate versus static cervical plate in the anterior cervical discectomy and fusion: a systematic review.

STUDY DESIGN AND OBJECTIVE: This study performs a systematic review to compare the functional outcomes and complications between the dynamic cervical plate and static cervical plate in patients with the anterior cervical discectomy and fusion (ACDF). The common static cervical plates have been widely used in the ACDF. It can successfully increase the fusion rate and decrease the surgery failure. Recently, the dynamic plate has been identified as another safe and efficient option for the better fusion rate by promoting load sharing across the construct. However, the proposed benefits have been largely theoretical, and there is considerable controversy as to which plate is a better option for reconstruction after ACDF. METHODS: We searched the Cochrane Library, EMBASE, PubMed, and CBM to identify the clinical studies regarding the comparison of dynamic cervical plate with fixed cervical plate in the ACDF. Reports not available in English were excluded. The quality of the included studies was critically assessed, and the data analysis was performed by the Cochrane Collaboration's RevMan 4.2. We defined statistical significance as a P value <0.05. RESULTS: Five studies were included in this systematic review. In the final analysis, there were 172 patients in the dynamic cervical plate and 143 in the static cervical group. Four studies compared the clinical and radiographic outcomes between the two plate groups in the one-level or two-level fusion segmentation patients, while one studied the patients with the multiple levels. The similar clinical outcomes between the two cervical plate systems were reported in two studies. However, another study suggested that a better clinical outcome was found in the dynamic plate group for the multiple-level fusion patients, although the similar clinical outcome was found in the one-level fusion patients. The two RCT studies with the same clinical data reported that four patients in the static group developed hardware complications, while there was no implant complication in the dynamic group. CONCLUSION: The clinical outcome was similar in ACDF for one-level fusion patients, although the hardware failure rate was higher in ACDF with static plates.

[Arthroscopic treatment of tibial intercondylar eminence fracture in children].

OBJECTIVE: To study clinical effects of extractable steel wire for the treatment of tibial intercondylar eminence fracture in children under arthroscopy. METHODS: From October 2008 to December 2010,21 children with intercondyloid eminence fractures were treated with fixation by extractable steel wire under arthroscopy. Among the patients, 14 patients were male and 7 patients were female,ranging in age from 7 to 14 years old with a mean of 10 years old. The period from injury to operation ranged from 3 to 8 days, with an average of 4 days. Before operation, X-ray, CT and MRI were used to determine fracture and joint injury type. Lysholm criteria were used to evaluate clinical effects. RESULTS: All fractures were healed. The Lysholm score improved from preoperative 30.2 +/- 4.2 to postoperative 92.8 +/- 9.1; 18 patients got an excellent result and 3 good. CONCLUSION: The extractable steel wire in treatment of tibial intercondyloid eminence fractures in children under arthroscopy has advantage of economics, firm fixation, in favour of early functional exercise, decreasing the opportunity of bony avulsion of the anterior cruciate ligament and less iatrogenic injury of osteoepiphysis due to small diameter and slick steel wire.

Levels of metalloproteinase (MMP-3, MMP-9), NF-kappaB ligand (RANKL), and nitric oxide (NO) in peripheral blood of osteoarthritis (OA) patients.

BACKGROUND: The aim of this study was to judge whether there is a correlation between some biochemical features of knee osteoarthritic blood and clinical characteristics and to evaluate the potential relationship between osteoarthitis (OA) severity and putative biomarkers for the disease. METHODS: 105 patients suffering from knee OA were analyzed clinically (Lequesne's index) and radiographically (Kellgren and Lawrence, K&L). Plasma and peripheral blood mononuclear cells (PBMC) were harvested separately. Specimens were analyzed for concentrations of nitric oxide (NO), matrix metalloproteinase-3 (MMP-3), and matrix metalloproteinase-9 (MMP-9). Transcript levels of the receptor activator of NF-kB ligand (RANKL) mRNA, MMP-3mRNA, and MMP-9mRNA were measured using real-time quantitative RT-PCR. RESULTS: Data certified significantly increasing concentrations of plasma MMP-3, MMP-9, and NO as well as transcript levels of RANKL mRNA and MMP-9 mRNA in early OA (at grade I). There was a positive correlation of MMP-3 and MMP-9 content in plasma and MMP-9 mRNA expression levels in PBMC with the severity of clinical symptoms (total Lequesne's scores) in early OA. NO content in plasma correlated with total Lequesne's scores, pain scores in response to pressure, and swelling scores of early OA patients (atgGrade I). Analogously, there were positive correlations of RANKL mRNA expression with total Lequesne's scores, pain scores in response to pressure, and swelling scores in OA patients at Grade I. CONCLUSIONS: [corrected] Some biochemical factors, including content of NO, MMP-3, MMP-9, and transcript levels of some genes, including MMP-9 mRNA and RANKL mRNA, may be specific and sensitive enough to diagnose OA diseases at an early stage in the pathological process of OA when radiological features do not reflect degradation of articular cartilage. Therefore, proper regulation of these factors may be a promising and realistic new target for the treatment of degenerative osteoarticular diseases.

[Serum levels of cartilage oligomeric matrix protein in the diagnosis of knee osteoarthritis].

OBJECTIVE: To select sub-clinical patients with symptoms of knee osteoarthritis (KOA) without X-ray changes by measuring the serum level of cartilage oligomeric matrix protein (COMP) with ELISA, so as to diagnose and treat patients with knee osteoarthritis at early stage. METHODS: The 115 patients with KOA or with symptomatic primary KOA were enrolled from August 2007 to September 2009, which was OA group; and 35 healthy people in the control group. In OA group, there were 55 males and 60 females,ranging in age from 39 to 76 years, with an average of (55 +/- 13.32) years; the body mass index (BMI) ranged from 15.1 to 29.8; the disease course ranged from 6 to 60 months. In the control group, there were 16 males and 19 females, ranging in age from 36 to 77 years, with an average of (53 +/- 12.53) years; the BMI ranged from 14.8 to 29.2. Patients with symptomatic primary knee OA of Kellgren-Lawrence (K-L) grade I-IV were evaluated. Serum level of COMP and its correlation with OA grade were analyzed by ELISA method. The patients were treated with Celecoxib capsules. The patients in OA group were followed up, and the duration ranged from 24 to 38 months (averaged, 33.4 months), and the serum level of COMP were analyzed before and after treatment. RESULTS: The serum level of COMP in the control group varied with age (t= 2.50, P=0.02). The serum level of COMP did not correlate with gender (control group: t=0.98, P=0.34; OA group: t=0.18, P= 0.86), BMI (control group: t=0.56, P=0.92; OA group: t=0.17, P=0.85) and smoking (control group: t=1.89, P=0.08; OA group: t=0.70, P=0.49). The serum level of COMP was higher in the patients with higher K-L grades than in the patients with lower K-L grades (F=15.56, P=0.001) . The sub-clinical KOA patients without X-ray changes can be detected significant higher COMP levels than sub-clinical patients with other diseases (t=2.55, P=0.03). Therefore, according to this method, subclinical OA patients can be detected from people with other sub-clinical diseases successfully. CONCLUSION: The serum level of COMP can be used as a potential prognostic marker to diagnose KOA.

[Repair of soft tissue defects on the lower limbs with the facial pedicled flap with vascular perforating branch of leg].

OBJECTIVE: To investigate the operative techniques and clinical results of the facial pedicled flap with vascular perforating branch of leg. METHODS: From May 1998 to January 2009,62 patients with soft tissue defects on the lower limbs were treated by four kinds of flap pedicled with the medial, posterior,anterolateral and posterolateral vascular perforating branches in the leg, included 50 males and 12 females, aged from 7 to 78 years old. There were 23 cases of the facial pedicled flap based on the perforating branch of the tibialis posterior artery, 9 cases of the facial pedicled flap based on the distal perforating branch of peroneal artery, 22 cases of the facial pedicled flap based on the peroneal artery perforator, 8 cases of the facial pedicled flap based on the lateral popliteal cutaneous artery. RESULTS: The remaining flaps were completely survived except for 2 cases with epidermal necrosis and scab of distal flap, and 1 case with skin necrosis and skingrafting later. The patients were followed-up for from 1 month to 3 years, the appearance of the flaps were satisfied and the function were good. CONCLUSION: The blood supply area of single perforator vascular of the leg is insufficient, so the presence facial pedicled flap of arterial chains will expend obviously the area of perforator flap that be good to blood supply and venous return.

[Changes of somatosensory and transcranial magnetic stimulation motor evoked potentials in experimental spinal cord injury].

OBJECTIVE: To study the changes of somatosensory evoked potential (SEP) and transcranial magnetic simulation motor evoked potential (TMS-MEP) in experimental spinal cord injury (SCI). METHODS: Thirty-two rabbits were randomly divided into 4 equal groups. All rabbits were anesthetized for 90 min. A group (Group A) underwent only laminectomy of T12 without SCI, stimulation with different intensities was used to induce SEP and TMS-MEP to determine the most appropriate stimulation intensity. The EPs were recorded before and after the operation. The other 3 groups underwent laminectomy of T12 to expose the dura, and a spinal cord compressing apparatus weighing 40 g was put on the intact dura and dorsal surface of spinal cord underneath for 5, 15, and 30 min respectively (Groups B, C, and D). SEP and TMS-MEP were detected after anesthesia, after exposure of spinal cord, and 5 and 30 min, 1 and 6 h, and 1, 3, and 7 d. The latency and amplitude of each wave were measured. The data were analyzed by analysis of variance, t-test and linear correlation. Tarlov behavior score was used to assess the motor function before the operation and 1, 3, and 7 days after SCI. RESULTS: It was found that 100% intensity stimulus obtained stable and reliable MEP waves. Anesthetic did not influence the EPs. The amplitude of SEP began to decrease 5 min after SCI and the latency began to increase 30 min after SCI. And both the amplitude and latency, especially the former, of MEP began to significantly change 5 min after SCI. The latency levels of SEP and MEP increased and the amplitude decreased after compression time-dependently during a certain range of time (all P <0. 05). The latency of SEP recovered 1 d after SCI and the amplitude recovered 7 d after; and the latency of MEP recovered 3 d after SCI and the amplitude did not recover even 7 d after SCI. The Tarlov scores of all groups were all 5 before operation, and the Tarlov scores of Group C and D became 1 d after operation and then increased later, however, still lower than 5 even at day 7. CONCLUSION: SEP and TMS-MEP are very sensitive to SCI, in particular, the change of amplitude is more sensitive then the latency change and can more accurately reflect the degree of SCI. Combination of SEP and TMS-MEP objectively reflects the SCI degree. EP measurement, as a noninvasive technique, has great value in monitoring spinal cord function.