These authors contributed equally to this work. Keywords: MicroRNA, osteoclast, osteoporosisAbbreviations: GM-CSF, Granulocyte macrophage colony-stimulating factor; MiRNA, microRNA; 3'-UTR; 3' untranslated region; BMMs, bone marrow macrophages; PDCD4, programmed cell death 4; FasL, Fas ligand; PIO, particle-induced osteolysis; Calcr, calcitonin receptor; RDX, radixin; M-RIP, myosin phosphatase-Rho interacting protein; ITGA5, integrin a5; Fzd3, frizzled 3; ALP, alkaline phosphatase; TRAP, tartrate-resistant acid phosphatase; CXCL11, chemokine (C-X-C motif) ligand 11; CXCR3, chemokine (C-X-C motif) receptor 3; SLC39A1, solute carrier family (zinc transporter) member 1; TRAF6, TNF receptor-associated factor 6; OVX, ovariectomy; MAFB, V-maf musculoaponeurotic fibrosarcoma oncogene homolog B; CBL, Casitas B-lineage lymphoma proto-oncogene; PAG1, phosphoprotein associated with glycosphingolipid microdomains; TOB2, transducer of ERBB2; sICAM1, soluble intracellular adhesion molecule.Osteoclasts are the exclusive cells of bone resorption. Abnormally activating osteoclasts can lead to low bone mineral density, which will cause osteopenia, osteoporosis, and other bone disorders. To date, the mechanism of how osteoclast precursors differentiate into mature osteoclasts remains elusive. MicroRNAs (miRNAs) are novel regulatory factors that play an important role in numerous cellular processes, including cell differentiation and apoptosis, by post-transcriptional regulation of genes. Recently, a number of studies have revealed that miRNAs participate in bone homeostasis, including osteoclastic bone resorption, which sheds light on the mechanisms underlying osteoclast differentiation. In this review, we highlight the miRNAs involved in regulating osteoclast differentiation and bone resorption, and their roles in osteoporosis.

BackgroundInfected nonunion of tibia and femur are common in clinical practice, however, the treatment of these diseases has still been a challenge for orthopaedic surgeons. Ilizarov methods can eradicate infection, compensate bone defects and promote the bone union through progressive bone histogenesis. The objective of this systematic review was to review current available studies reporting on Ilizarov methods in the treatment of infected nonunion of tibia and femur, and to perform meta-analysis of bone and functional results and complications to evaluate the efficacy of Ilizarov methods.MethodsA comprehensive literature search was performed from the SCI, PubMed, Cochrane Library; and Embase between January 1995 and August 2015. Some major data were statistically analyzed using weighted means based on the sample size in each study by SPSS 13.0, including number of patients, mean age, mean previous surgical procedures, mean bone defects, mean length of follow-up, bone union, complications per patient, external fixation time, and external fixation index(EFI). Bone results (excellent, good, fair and poor rate), functional results (excellent, good, fair and poor rate) and complications were analyzed by Stata 9.0.FindingsA total of 590 patients from 24 studies were included in this systematic review. The average of bone union rate was 97.26% in all included studies. The poor rate in bone results and functional results was 8% (95%CI, 0.04–0.12; I2 = 44.1%, P = 0.065) and 10% (95%CI, 0.05–0.14; I2 = 34.7%, P = 0.121) in patients with infected nonunion of tibia and femur treated by Ilizarov methods. The rate of refracture, malunion, infectious recurrence, knee stiffness, amputation, limb edema and peroneal nerve palsy was respectively 4%, 7%, 5%, 12%, 4%, 13% and 13%.ConclusionsOur systematic review showed that the patients with infected nonunion of tibia and femur treated by Ilizarov methods had a low rate of poor bone and functional results. Therefore, Ilizarov methods may be a good choice for the treatment of infected nonunion of tibia and femur.

ObjectiveThe objective of this study was to evaluate the effectiveness of the treatment of infected nonunion of tibia and femur by bone transport.Material and methodsWe retrospectively reviewed 110 patients with infected nonunion of tibia and femur treated by bone transport. Our study included 92 males and 18 females with a mean age of 38.90 years. The site of infected nonunion involved 72 tibias and 38 femurs. The mean length of the bone defects after radical debridement was 6.15 cm (range 3–13 cm).ResultsThe mean follow-up after removal of the apparatus was 23.12 months (14–46 months). Ten patients including seven patients with infected tibia nonunion and three patients with infected femur nonunion were lost to follow-up. All the patients achieved bone union, and no recurrence of infection was observed. The time of bone transport took a mean of 67.50 days (range 33 to 137 days), and the mean external fixation index was 1.48 months/cm (range 1.15–1.71 months/cm). According to Association for the Study and Application of the Method of Ilizarov (ASAMI) classification, bone results were excellent in 68, good in 28, fair in 12, and poor in 2; functional results were excellent in 37, good in 42, fair in 21, and no poor.ConclusionsOur study and the current evidence suggested that Ilizarov methods in the treatment of infected nonunion of tibia and femur acquired satisfied results. Radical debridement is the key step to control bone infection.

Curcumin, phloretin and structurally related phytopolyphenols have well-described neuroprotective properties that appear to be at least partially mediated by 1,3-dicarbonyl enol substructures that form nucleophilic enolates. Based on their structural similarities, we tested the hypothesis that enolates of simple 1,3-dicarbonyl compounds such as acetylacetone might also possess neuroprotective actions. Our results show that the b-diketones, particularly 2-acetylcyclopentanone, protected rat striatal synaptosomes and a neuronal cell line from thiol loss and toxicity induced by acrolein, an electrophilic a,b-unsaturated aldehyde. The 1,3-dicarbonyl compounds also provided substantial cytoprotection against toxicity induced by hydrogen peroxide in a cellular model of oxidative stress. Initial chemical characterization in cell-free systems indicated that the 1,3-dicarbonyl compounds acted as surrogate nucleophilic targets that slowed the rate of sulfhydryl loss caused by acrolein. Although the selected 1,3-dicarbonyl congeners did not scavenge free radicals, metal ion chelation was a significant property of both acetylacetone and 2-acetylcyclopentanone. Our data suggest that the 1,3-dicarbonyl enols represent a new class of neuroprotectants that scavenge electrophilic metal ions and unsaturated aldehydes through their nucleophilic enolate forms. As such, these enols might be rational candidates for treatment of acute or chronic neurodegenerative conditions that have oxidative stress as a common molecular etiology.

Despite the systemic antibiotics prophylaxis, orthopedic implants still remain highly susceptible to bacterial adhesion and resulting in device-associated infection. Surface modification is an effective way to decrease bacterial adhesion. In this study, we prepared surfaces with different wettability on titanium surface based on TiO2nanotube to examine the effect of bacterial adhesion. Firstly, titanium plates were calcined to form hydrophilic TiO2nanotube films of anatase phase. Subsequently, the nanotube films and inoxidized titaniums were treated with 1H, 1H, 2H, 2H-perfluorooctyl-triethoxysilane (PTES), forming superhydrophobic and hydrophobic surfaces. Observed by SEM and contact angle measurements, the different surfaces have different characteristics.Staphylococcus aureus(SA) adhesion on different surfaces was evaluated. Our experiment results show that the superhydrophobic surface has contact angles of water greater than 150∘and also shows high resistance to bacterial contamination. It is indicated that superhydrophobic surface may be a factor to reduce device-associated infection and could be used in clinical practice.

α,β-Unsaturated carbonyls are an important class of chemicals involved in environmental toxicity and disease processes. Whereas adduction of cysteine residues on proteins is a well-documented reaction of these chemicals, such a generic effect cannot explain the molecular mechanism of cytotoxicity. Instead, more detailed information is needed regarding the possible specificity and kinetics of cysteine targeting and the quantitative relationship between adduct burden and protein dysfunction. To address these datagaps, purified human glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was incubated with acrylamide (ACR), acrolein or methylvinyl ketone (MVK). Results show that these α,β-unsaturated carbonyl toxicants inhibited GAPDH activity in a concentration-and time-dependent manner. The rank order of enzyme inhibition (KI); i.e., ACR << MVK < acrolein, was related to the calculated electrophilic reactivity of each compound and to the corresponding kinetics of cysteine adduct formation. Tandem mass spectrometry revealed that adduct formation was selective at lower concentrations; i.e., ACR preferentially formed adducts with Cys152 (residues 146-162). At higher concentrations, ACR also formed adducts with Cys156 and Cys247 (residues 235-248). Adduct formation at Cys152 was correlated to enzyme inhibition, which is consistent with the regulatory role of this residue in enzyme function and its location within the GAPDH active site. Further analyses indicated that Cys152 was present in a pKa-lowering microenvironment (pKa = 6.03) and, at physiological pH, the corresponding sulfhydryl group exists in the highly reactive nucleophilic thiolate-state. These data suggest a general cytotoxic mechanism where electrophilic α,β-unsaturated carbonyls selectively form adducts with reactive nucleophilic cysteine residues specifically associated with the active sites of proteins. These specialized cysteine residues are toxicologically relevant molecular targets, since chemical derivitization causes loss of protein function.

Objective: The aim of this study was to validate a novel pictorial-based Longshi Scale for evaluating a patient’s disability by healthcare professionals and non-professionals. Design: Prospective study. Setting: Rehabilitation departments from a grade A, class 3 public hospital, a grade B, class 2 public hospital, and a private hospital and seven community rehabilitation centers. Subjects: A total of 618 patients and 251 patients with functional disabilities were recruited in a two-phase study, respectively. Main measures: Outcome measure: pictorial scale of activities of daily living (ADLs, Longshi Scale). Reference measure: Barthel Index. The Spearman correlation coefficient was used to analyze the validity of Longshi Scale against Barthel Index. Results: In phase 1 study, from March 2016 to August 2016, the results demonstrated that the Longshi Scale was both reliable and valid (intraclass correlation coefficient based on two-way random effect (ICC2,1) = 0.877–0.974 for intra-rater reliability; ICC2,1 = 0.928–0.979; κ = 0.679–1.000 for inter-rater reliability; intraclass correlation coefficient based on one-way random effect (ICC1,1) = 0.921–0.984 for test–retest reliability and Spearman correlation coefficient = 0.836–0.899). In the second phase, in March 2018, results further demonstrated that the Longshi Scale had good inter-rater and intra-rater reliability among healthcare professionals and non-professionals including therapists, interns, and personal care aids (ICC1,1 = 0.822–0.882 on Day 1; ICC1,1 = 0.842–0.899 on Day 7 for inter-rater reliability). In addition, the Longshi Scale decreased assessment time significantly, compared with the Barthel Index assessment ( P < 0.01). Conclusion: The Longshi Scale could potentially provide an efficient way for healthcare professionals and non-professionals who may have minimal training to assess the ADLs of functionally disabled patients.

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