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Conclusion Incorporation of doxorubicin-loaded microbubble in the TACE formulation facilitated drug delivery to the tumor with real-time monitoring and enhanced the therapeutic efficacy of TACE. Thus, the enhanced TACE formulation may represent a new treatment strategy against liver cancer.Background Conventional therapeutic strategies for advanced hepatocellular carcinoma (HCC) remains a great challenge, therefore the alternative therapeutic modality for specific and efficient HCC suppression is urgently needed. Methods In this work, HCC-derived extracellular vesicles (EVs) were applied as surface nanocarrier for sequential nanocatalysts GOD-ESIONs@EVs (GE@EVs) of tumor-specific and cascade nanocatalytic therapy against HCC. By enhancing the intracellular endocytosis through arginine-glycine-aspartic acid (RGD)-targeting effect and membrane fusion, sequential nanocatalysts led to more efficient treatment in the HCC tumor region in a shorter period of time. Results Through glucose consumption as catalyzed by the loaded glucose oxidase (GOD) to overproduce hydrogen peroxide (H2O2), highly toxic hydroxyl radicals were generated by Fenton-like reaction as catalyzed by ESIONs, which was achieved under the mildly acidic tumor microenvironment, enabling the stimuli of the apoptosis and necrosis of HCC cells. This strategy demonstrated the high active-targeting capability of GE@EVs into HCC, achieving highly efficient tumor suppression both in vitro and in vivo. In addition, the as-synthesized nanoreactor could act as a desirable nanoscale contrast agent for magnetic resonance imaging, which exhibited desirable imaging capability during the sequential nanocatalytic treatment. Conclusion This application of surface-engineering EVs not only proves the high-performance catalytic therapeutic modality of GE@EVs for HCC, but also broadens the versatile bio-applications of EVs.The most important requirements of biomedical substitutes used in muscle tissue regeneration are appropriate topographical cues and bioactive components for the induction of myogenic differentiation/maturation. Here, we developed an electric field-assisted 3D cell-printing process to fabricate cell-laden fibers with a cell-alignment cue. Methods We used gelatin methacryloyl (GelMA) laden with C2C12 cells. The cells in the GelMA fiber were exposed to electrical stimulation, which induced cell alignment. Various cellular activities, such as cell viability, cell guidance, and proliferation/myogenic differentiation of the microfibrous cells in GelMA, were investigated in response to parameters (applied electric fields, viscosity of the bioink, and encapsulated cell density). In addition, a cell-laden fibrous bundle mimicking the structure of the perimysium was designed using gelatin hydrogel in conjunction with a 4D bioprinting technique. Results Cell-laden microfibers were fabricated using optimized process parameters (electric field intensity = 0.8 kV cm-1, applying time = 12 s, and cell number = 15 × 106 cells mL-1). Sotuletinib research buy The cell alignment induced by the electric field promoted significantly greater myotube formation, formation of highly ordered myotubes, and enhanced maturation, compared to the normally printed cell-laden structure. The shape change mechanism that involved the swelling properties and folding abilities of gelatin was successfully evaluated, and we bundled the GelMA microfibers using a 4D-conceptualized gelatin film. Conclusion The C2C12-laden GelMA structure demonstrated effective myotube formation/maturation in response to stimulation with an electric field. Based on these results, we propose that our cell-laden fibrous bundles can be employed as in vitro drug testing models for obtaining insights into the various myogenic responses.Low back pain (LBP) is a major reason for disability, and symptomatic intervertebral disc (IVD) degeneration (IDD) contributes to roughly 40% of all LBP cases. Current treatment modalities for IDD include conservative and surgical strategies. Unfortunately, there is a significant number of patients in which conventional therapies fail with the result that these patients remain suffering from chronic pain and disability. Furthermore, none of the current therapies successfully address the underlying biological problem - the symptomatic degenerated disc. Both spinal fusion as well as total disc replacement devices reduce spinal motion and are associated with adjacent segment disease. Thus, there is an unmet need for novel and stage-adjusted therapies to combat IDD. Several new treatment options aiming to regenerate the IVD are currently under investigation. The most common approaches include tissue engineering, growth factor therapy, gene therapy, and cell-based treatments according to the stage of degeneration. Recently, the regenerative activity of small molecules (low molecular weight organic compounds with less than 900 daltons) on IDD was demonstrated. However, small molecule-based therapy in IDD is still in its infancy due to limited knowledge about the mechanisms that control different cell signaling pathways of IVD homeostasis. Small molecules can act as anti-inflammatory, anti-apoptotic, anti-oxidative, and anabolic agents, which can prevent further degeneration of disc cells and enhance their regeneration. This review pursues to give a comprehensive overview of small molecules, focusing on low molecular weight organic compounds, and their potential utilization in patients with IDD based on recent in vitro, in vivo, and pre-clinical studies.Rationale Liver fibrosis is frequently associated with gut barrier dysfunction, and the lipopolysaccharides (LPS) -TLR4 pathway is common to the development of both. Intestinal alkaline phosphatase (IAP) has the ability to detoxify LPS, as well as maintain intestinal tight junction proteins and gut barrier integrity. Therefore, we hypothesized that IAP may function as a novel therapy to prevent liver fibrosis. Methods Stool IAP activity from cirrhotic patients were determined. Common bile duct ligation (CBDL) and Carbon Tetrachloride-4 (CCl4)-induced liver fibrosis models were used in WT, IAP knockout (KO), and TLR4 KO mice supplemented with or without exogenous IAP in their drinking water. The gut barrier function and liver fibrosis markers were tested. Results Human stool IAP activity was decreased in the setting of liver cirrhosis. In mice, IAP activity and genes expression decreased after CBDL and CCl4 exposure. Intestinal tight junction related genes and gut barrier function were impaired in both models of liver fibrosis.
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