Summary Objectives To investigate the association of ultrasound (US) features with pain and the functional scores in patients with equal radiographic grades of osteoarthritis (OA) in both knees. ...Methods Fifty-six consecutive patients with knee OA: 85 symptomatic knees (81 knees with medial pain) and 27 asymptomatic knees, and 10 healthy patients without knee OA as a control were enrolled. US was done by two ultrasonographers blinded to patient diagnoses. US features were semiquantitatively scored (0–3) when appropriate. Results In the OA group, common US findings were marginal osteophyte, suprapatellar synovitis, suprapatellar effusion (SPE), medial meniscus protrusion, medial compartment synovitis (MCS), lateral compartment synovitis, and Baker's cyst. Only SPE and MCS were significantly associated with knee pain. Visual analog pain scale (VAS) scores on motion were positively linearly associated with SPE and MCS ( P < 0.01). Only MCS was degree-dependently associated with VAS scores at rest, the Western Ontario and McMaster Universities pain subscale, and the presence of medial knee pain ( P < 0.01) after adjustments for age, gender, body mass index (BMI), radiographic grade, and other US features. In the control group, no US features were associated with knee pain. Conclusions US inflammation features, including SPE and MCS, were positively linearly associated with knee pain in motion. MCS was also degree-dependently associated with pain at rest and the presence of medial knee pain. These findings show that synovitis was one important predictive factor of pain. Further studies to confirm the association of US features and pain are warranted.
Summary Objective Immune cells are involved in the pathogenesis of osteoarthritis (OA). We examined the effects of T helper (Th) cells, which induce the expression of macrophage inflammatory protein ...(MIP-1γ), on the progression of OA. Design Using anterior cruciate ligament-transection (ACLT), we induced OA in one hind-leg knee joint of B6 mice. The CD4+ T cells from splenocytes and synovium were flow-cytometrically and immunochemically evaluated, respectively. The knee joints were histologically assessed for manifestations of OA. MIP-1γ levels and nuclear factor-κB (NF-κB) in the knee joints were measured using enzyme-linked immunosorbent and immunoblotting assays, respectively; osteoclastogenesis was detected by tartrate-resistant acid phosphatase (TRAP) staining. The inflammatory responses and MIP-1γ expression were examined using immunohistochemistry. Results The number of CD4+ T cells and the expression of interferon-γ (IFN-γ) increased during OA onset (30 days after ACLT) and then decreased at a later stage of OA (90 days after ACLT). Tissue damage induced by CD4+ T cells was evident at the later stage. The activation of CD4+ T cells induced the expression of MIP-1γ and NF-κB. The expression of MIP-1γ can be detected in synovium which CD4+ T cells were infiltrated. The increased MIP-1γ expression caused an increase in the number of osteoclasts in joints. The regulation of CD4+ T cells was accompanied by increased macrophage infiltration and matrix metalloproteinase (MMP)-9 expression. Histopathological examinations revealed that CD4+ T cell knockout (CD4−/− ) mice had less expression of MIP-1γ and slower cartilage degeneration than control mice had. Conclusions CD4+ T cells were activated during the onset of OA, but cartilage damage was more prominent at a later stage. CD4+ T cells were involved in the pathogenesis of OA: they induced MIP-1γ expression and subsequent osteoclast formation.
Atherosclerosis is a process of imbalanced lipid metabolism in the vascular walls. The underlying pathology mainly involves the deposition of oxidized lipids in the endothelium and the accumulation ...of cholesterol in macrophages. Macrophages export excessive cholesterol (cholesterol efflux) through ATP-binding cassette transporter A1 (ABCA1) to counter the progression of atherosclerosis. We synthesized novel chalcone derivatives and assessed their effects and the underlying mechanisms on ABCA1 expression in macrophages. Human THP-1 macrophages were treated with synthetic chalcone derivatives for 24 h. In Western blot and flow cytometry analyses, a chalcone derivative, (
)-
(
), was observed to significantly enhance ABCA1 protein expression in THP-1 cells (10 µM, 24 h). Levels of mRNA of ABCA1 and liver X receptor alpha (LXRα) were quantified using a real-time quantitative polymerase chain reaction technique and were found to be significantly increased after treatment with the novel chalcone derivative
. Several microRNAs, including miR155, miR758, miR10b, miR145, miR33, and miR106b, which functionally inhibit ABCA1 expression were suppressed after treatment with 1m. Collectively, 1m increases ABCA1 expression in human THP-1 macrophages. The mechanisms involve the activation of the LXRα-ABCA1 pathway and suppression of certain microRNAs that regulate ABCA1 expression.
We compared the accuracy of the fluoroscopic dorsal tangential view (DTV) and an ultrasound (US) examination in detecting dorsal screw penetration during volar distal radius plating. In six fresh ...cadaveric distal radii, seven periarticular locking screws in two rows for each plate were inserted according to the measured length using a depth gauge and then replaced with another that was 1 and 2 mm longer, respectively. The actual protruded length of each screw was determined using computed tomography (CT) images. The accuracy of US and DTV measurements was determined using the intraclass correlation coefficient (ICC), as both measurements were compared with CT measurements. The ICC of US and DTV was 0.96 and 0.75, respectively, for all screws. After excluding the data for proximal‐row screws, the ICC of US remained unchanged at 0.96, and that of DTV improved to 0.86. The ICC of US was significantly higher than that of DTV (p < 0.01). US had a 100% detection rate for screw protrusion of more than 1.0 mm. US examination showed excellent consistency with CT measurements and its accuracy was not affected by screw location. US might thus be a practical tool for detecting dorsal cortex screw penetration during volar distal radius plating.
Caregiver rating scales often give an unclear picture of the actual self-care performance of preschool children with autism spectrum disorder (ASD).
To assess self-care performance among preschool ...children with ASD using two standardized instruments.
Cross-sectional study.
Clinics, hospitals, and early intervention centers in Tainan, Taiwan.
Sixty children with ASD (ages 48-71 mo). Outcomes and Measures: The Standard Version of the Childhood Autism Rating Scale-Second Edition, the Assessment of Motor and Process Skills (AMPS), and the Chinese version of the Pediatric Evaluation of Disability Inventory (PEDI-C).
About 53.3% of children with ASD scored below 1.5 logits for AMPS motor skills and below 1 logit for AMPS process skills, indicating difficulties performing activities of daily living tasks. The average PEDI-C self-care normative standard scores were moderately low (between -1 and -2 SDs), indicating poor self-care performance. The correlations between the two measures were also low (rs = .27-.44). Overall, the results for 36 children were consistent with AMPS and PEDI-C scores; however, those for 24 children (40.0%) were discrepant.
These findings have implications for how preschool children with ASD perform their self-care activities and suggest that more than half of preschool children with ASD have a need for occupational therapy interventions that target self-care skills. Occupational therapy practitioners can work with preschool children with ASD and their families to help them improve their self-care performance. What This Article Adds: Many children with ASD need occupational therapy interventions that target self-care skills. Both the AMPS and the PEDI-C provide valuable information from different perspectives on the self-care performance of preschool children with ASD.
Although the height of the proliferating layer that was suppressed in the growth plate has been recognized as an adverse effect of cisplatin in pediatric cancer survivors, the detailed pathological ...mechanism has not been elucidated. Sirtuin-1 (SIRT1) has been reported as an essential modulator of cartilage homeostasis, but its role in cisplatin-induced damage of chondrocytes remains unclear. In this study, we examined how cisplatin affected the expression of SIRT1 and cell viability. Next, we showed downregulation of SIRT1 after cisplatin treatment resulted in suppression of Peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α), leading to inhibition of Nrf2 nuclear translocation and subsequently decreased Heme oxygenase-1(HO-1) and NAD(P)H Quinone Dehydrogenase 1(NQO-1) expression. Blockage of the SIRT1/ PGC-1α axis not only increased oxidative stress with lower antioxidant SOD and GSH, but also contributed to mitochondrial dysfunction evidenced by the collapse of membrane potential and repression of mitochondrial DNA copy number and ATP. We also found that Cisplatin up-regulated the p38 phosphorylation, pro-inflammatory events and matrix metalloproteinases (MMPs) in chondrocytes through the SIRT1-modulated antioxidant manner. Collectively, our findings suggest that preservation of SIRT1 in chondrocytes may be a potential target to ameliorate growth plate dysfunction for cisplatin-receiving pediatric cancer survivors.
Osteoarthritis (OA) is a common degenerative joint disease. The pathological changes of chondrocytes involve oxidative stress, the pro‐inflammatory response, and pro‐apoptotic events. Galectin‐3 ...(Gal‐3) is a 35 kDa protein with a special chimeric structure. Gal‐3 participates in the progression of many diseases, such as cancer metastasis and heart failure. A previous study demonstrated that Gal‐3 expression in human cartilage with OA is increased. However, the role of Gal‐3 in chondrocyte dysfunction in joints is still unclear. In this study, we applied Gal‐3 (5–20 μg/ml) to TC28a2 human chondrocyte cells for 24 h to induce chondrocyte dysfunction. We found that Gal‐3 upregulated TLR‐4 and MyD88 expression and NADPH oxidase, thereby increasing intracellular ROS in the chondrocytes. Gal‐3 increased phosphorylated MEK1/2 and ERK levels, and promoted NF‐κB activity. This activation of NF‐κB was reduced by silencing TLR‐4 and NOX‐2. In addition, Gal‐3 caused apoptosis of chondrocytes through the mitochondrial‐dependent pathway via the TLR‐4/NADPH oxidase/MAPK axis. Our study proves the pathogenic role of Gal‐3 in Gal‐3‐induced chondrocyte dysfunction and injuries.
Reporter proteins have broad applications in visualizing molecular events at the cellular, tissue and whole‐body levels. Transmembrane transporters recognizing specific molecular domains are of ...particular interest because they enable the migration of signal‐source molecules from the extracellular space to the cytoplasm for subsequent application in multimodality imaging. Organic anion‐transporting polypeptides (OATPs) have demonstrated their MRI reporter efficacy. We further expanded their use as a dual‐modality reporter in MRI and noninvasive in vivo imaging system (IVIS). We overexpressed OATP1B3 in the HT‐1080 sarcoma cell line. Both Gd‐EOB‐DTPA, an MRI contrast agent, and indocyanine green (ICG), a near‐infrared fluorescent dye that provides better deep‐tissue detection because of its long wavelength, could be delivered to the intracellular space and imaged in a tumor‐bearing nude mouse model. Our in vivo dual‐imaging reporter system achieved high sensitivity in MRI and observation periods lasting as long as 96 h in IVIS. Because of the superior temporal and spatial resolutions and the clinical availability of both ICG and Gd‐EOB‐DTPA, this dual‐imaging OATP1B3 system will find biomedical use in tumor biology, stem cell trafficking, and tissue engineering.—Wu, M.‐R., Liu, H.‐M., Lu, C.‐W., Shen, W.‐H., Lin, I.‐J., Liao, L.‐W., Huang, Y.‐Y., Shieh, M.‐J., Hsiao, J.‐K. Organic anion‐transporting polypeptide 1B3 as a dual reporter gene for fluorescence and magnetic resonance imaging. FASEB J. 32,1705‐1715 (2018). www.fasebj.org
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