Advanced ovarian cancer usually spreads to the visceral adipose tissue of the omentum. However, the omental stromal cell-derived molecular determinants that modulate ovarian cancer growth have not been characterized. Here, using next-generation sequencing technology, we identify significantly higher levels of microRNA-21 (miR21) isomiRNAs in exosomes and tissue lysates isolated from cancer-associated adipocytes (CAAs) and fibroblasts (CAFs) than in those from ovarian cancer cells. Functional studies reveal that miR21 is transferred from CAAs or CAFs to the cancer cells, where it suppresses ovarian cancer apoptosis and confers chemoresistance by binding to its direct novel target, APAF1. These data suggest that the malignant phenotype of metastatic ovarian cancer cells can be altered by miR21 delivered by exosomes derived from neighbouring stromal cells in the omental tumour microenvironment, and that inhibiting the transfer of stromal-derived miR21 is an alternative modality in the treatment of metastatic and recurrent ovarian cancer.
Proper immune responses are critical for successful biomaterial implantation. Here, four scales of honeycomb-like TiO2 structures were custom made on titanium (Ti) substrates to investigate cellular behaviors of RAW 264.7 macrophages and their immunomodulation on osteogenesis. We found that the reduced scale of honeycomb-like TiO2 structures could significantly activate the anti-inflammatory macrophage phenotype (M2), in which the 90-nanometer sample induced the highest expression level of CD206, interleukin-4, and interleukin-10 and released the highest amount of bone morphogenetic protein-2 among other scales. Afterward, the resulting immune microenvironment favorably triggered osteogenic differentiation of murine mesenchymal stem cells in vitro and subsequent implant-to-bone osteointegration in vivo. Furthermore, transcriptomic analysis revealed that the minimal scale of TiO2 honeycomb–like structure (90 nanometers) facilitated macrophage filopodia formation and up-regulated the Rho family of guanosine triphosphatases (RhoA, Rac1, and CDC42), which reinforced the polarization of macrophages through the activation of the RhoA/Rho–associated protein kinase signaling pathway.
One of the newest carbon allotropes synthesized are diamond nanothreads. Using molecular dynamics, we determine the stiffness (850 GPa), strength (26.4 nN), extension (14.9%), and bending rigidity (5.35 × 10(-28) N·m(2)). The 1D nature of the nanothread results in a tenacity of 4.1 × 10(7) N·m/kg, exceeding nanotubes and graphene. As the thread consists of repeating Stone-Wales defects, through steered molecular dynamics (SMD), we explore the effect of defect density on the strength, stiffness, and extension of the system.
BackgroundBracing has been shown to decrease significantly the progression of high-risk curves to the threshold for surgery in patients with adolescent idiopathic scoliosis (AIS), but the treatment failure rate remains high. There is evidence to suggest that Schroth scoliosis-specific exercises can slow progression in mild scoliosis. The aim of this study was to evaluate the efficacy of Schroth exercises in AIS patients with high-risk curves during bracing.MethodsA prospective, historical cohort-matched study was carried out. Patients diagnosed with AIS who fulfilled the Scoliosis Research Society (SRS) criteria for bracing were recruited to receive Schroth exercises during bracing. An outpatient-based Schroth program was given. Data for these patients were compared with a 1:1 matched historical control group who were treated with bracing alone. The assessor and statistician were blinded. Radiographic progression, truncal shift, and SRS-22r scores were compared between cases and controls.ResultsTwenty-four patients (5 males and 19 females, mean age 12.3 ± 1.4 years) were included in the exercise group, and 24 patients (mean age 11.8 ± 1.1 years) were matched in the control group. The mean follow-up period for the exercise group was 18.1 ± 6.2 months. In the exercise group, spinal deformity improved in 17% of patients (Cobb angle improvement of ≥ 6°), worsened in 21% (Cobb angle increases of ≥ 6°), and remained stable in 62%. In the control group, 4% improved, 50% worsened, and 46% remained stable. In the subgroup analysis, 31% of patients who were compliant (13 cases) improved, 69% remained static, and none had worsened, while in the non-compliant group (11 cases), none had improved, 46% worsened, and 46% remained stable. Analysis of the secondary outcomes showed improvement of the truncal shift, angle of trunk rotation, the SRS function domain, and total scores in favor of the exercise group.ConclusionThis is the first study to investigate the effects of Schroth exercises on AIS patients during bracing. Our findings from this preliminary study showed that Schroth exercise during bracing was superior to bracing alone in improving Cobb angles, trunk rotation, and QOL scores. Furthermore, those who were compliant with the exercise program had a higher rate of Cobb angle improvement. The results of this study form the basis for a randomized controlled trial to evaluate the effect of Schroth exercises during bracing in AIS.Trial registration HKUCTR-2226. Registered 22 June 2017 (retrospectively registered)
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