Various cancer metastasis models based on organ-on-a-chip platforms have been established to study molecular mechanisms and screen drugs. However, current platforms can neither reveal hypoxia-induced cancer metastasis mechanisms nor allow drug screening under a hypoxia environment on a multiorgan level. We have developed a three-dimensional-culture multiorgan microfluidic (3D-CMOM) platform in which the dissolved oxygen concentration can be precisely controlled. An organ-level lung cancer and liver linkage model was established under normoxic/hypoxic conditions. A transcriptomics analysis of the hypoxia-induced lung cancer cells (A549 cells) on the platform indicated that the hypoxia-inducible factor 1α (HIF-1α) pathway could elevate epithelial-mesenchymal transition (EMT) transcription factors (Snail 1 and Snail 2), which could promote cancer metastasis. Then, protein detection demonstrated that HIF-1α and EMT transcription factor expression levels were positively correlated with the secretion of cancer metastasis damage factors alphafetoprotein (AFP), alkaline phosphatase (ALP), and gamma-glutamyl transpeptidase (γ-GT) from liver cells. Furthermore, the cancer treatment effects of HIF-1α inhibitors (tirapazamine, SYP-5, and IDF-11774) were evaluated using the platform. The treatment effect of SYP-5 was enhanced under the hypoxic conditions with fewer side effects, similar to the findings of TPZ. We can envision its wide application in future investigations of cancer metastasis and screening of drugs under hypoxic conditions with the potential to replace animal experiments.
BackgroundArthroscopic ankle arthrodesis (AAA) is recognized as the standard treatment for the end-stage ankle arthritis. Two-screw configuration fixation is a typical technique for AAA; however, no consensus has been reached on how to select most suitable inserted position and direction. For better joint reduction, we developed a new configuration (2 home run-screw configuration: 2 screws are inserted from the lateral-posterior and medial-posterior malleolus into the talar neck) and investigated whether it turned out to be better than the other commonly used 2-screw configurations.MethodsIn this study, we investigated three kinds of 2-screw configurations: 2 “home run”-screw configuration (group A), crossed transverse configuration (the screw is inserted from the medial malleolus into the anterior talus and the other from the lateral tibia maintains posterior talus, group B), and 2 parallel screw configuration (2 parallel screws are inserted from the posteromedial side of the tibia into talus, group C). The effects of the above three insertions on the loading stress of the tibio-talar joint were comparatively analyzed with a three-dimensional finite element model.ResultsGroup A was better than groups B and C in respect of stress distribution uniformity and superior to both groups B and C in anti-flexion strength and anti-internal rotation strength. Group A was slightly worse than group C but better than group B in anti-dorsiflexion and anti-valgus and varus strength.ConclusionsTwo “home run”-screw configuration facilitates the reduction of anterior talus dislocation of end-stage ankle arthritis. Our finite element analysis demonstrates the configuration is superior to crossed transverse and parallel configuration for arthroscopic ankle arthrodesis in terms of stress distribution and initial stability.
BackgroundThe aim of this study was to determine whether the local application of tendon stem cells (TSCs) with chitosan/b-glycerophosphate/collagen(C/GP/Co) hydrogel promotes healing after an acute Achilles tendon injury in a rat model.Material/MethodsNinety-six Sprague-Dawley (SD) rats were used to make an Achilles tendon defect model, then the animals were randomly divided into 4 groups consisting of 8 rats each: control group, hydrogel group, TSCs group, and TSCs with hydrogel group. At 2, 4, and 6 weeks after treatment, tendon samples were harvested, and the quality of tendon repair was evaluated based on histology, immunohistochemistry, and biomechanical properties.ResultsCombining TSCs with C/GP/Co hydrogel significantly enhances tendon healing compared with the control, hydrogel, and TSCs groups. The improved healing was indicated by the improvement in histological and immunohistochemistry outcomes and the increase in the biomechanical properties of the regenerated tissue at both 4 and 6 weeks post-injury.ConclusionsThis study demonstrates that the transplantation of TSCs combined with C/GP/Co hydrogel significantly improved the histological, immunohistochemistry, and biomechanical outcomes of the regenerated tissue at 4 and 6 weeks after implantation. TSCs with C/GP/Co hydrogel is a potentially effective treatment for tendon injury.
Muscle damage is a common form of injury. The incidence of muscle damage accounts for up to half of the sports injuries. The aim of this study was to investigate the effect of pulsed ultrasound on the healing process in an animal contusion injury model. SD rats (62) were randomly divided into control group (CG, 14 rats) and treatment group (48). According to the intensities of Ultrasound therapy, the treatment group was divided into 4 subgroups of 12 rats, each: A (0.25 W/cm(2), US(1)), B (0.5 W/cm(2), US(2)), C (0.75 W/cm(2), US(3)) and D (0.25 W/cm(2)). The effectiveness of ultrasound treatment on muscle injuries was evaluated, and the optimal intensity of ultrasound in treating muscle injuries was explored. The results obtained provide experimental and theoretical evidence for the clinical effectiveness of Ultrasound therapy in treating muscle injuries.
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