Theranostics
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Rational: In a subset of cancers, arginine auxotrophy occurs due to the loss of expression of argininosuccinate synthetase 1 (ASS1). This loss of ASS1 expression makes cancers sensitive to arginine starvation that is induced by PEGylated arginine deiminase (ADI-PEG20). Although ADI-PEG20 treatment is effective, it does have important limitations. ⋯ Furthermore, in vivo PET imaging studies in mice with arginine-dependent osteosarcoma xenografts showed increased [18F]AFETP uptake in tumors 4 days after ADI-PEG20 treatment compared to baseline. Conclusion: CAT-1 transporters localizes to the plasma membrane as a result of arginine starvation with ADI-PEG20 in ASS1-deficient tumor cells and provides a mechanism for using cationic amino acid transport substrates such as [18F]AFETP for identifying tumors susceptible to ADI-PEG20 treatment though non-invasive PET imaging techniques. These findings indicate that [18F]AFETP-PET may be suitable for the early detection of tumor response to arginine depletion due to ADI-PEG20 treatment.
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Acute spinal cord injury (SCI) induces secondary hemorrhage and initial blood-spinal cord barrier (BSCB) disruption. The transient receptor potential melastatin 4 (Trpm4) together with sulfonylurea receptor 1 (Sur1) forms the Sur1-Trpm4 channel complex. The up-regulation of Sur1-Trpm4 after injury plays a crucial role in secondary hemorrhage, which is the most destructive mechanism in secondary injuries of the central nervous system (CNS). ⋯ Finally, FFA protected motor neurons and improved locomotor functions after SCI. Conclusion: This study indicates that FFA improves functional recovery, in part, due to the following reasons: (1) it inhibits the expression of Trpm4 to reduce the secondary hemorrhage; and (2) it inhibits the expression of MMP-2 and MMP-9 to block BSCB disruption. Thus, the results of our study suggest that FFA may represent a potential therapeutic agent for promoting functional recovery.
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Pre-vascularised cell sheets have been used to promote early angiogenesis and graft survival. However, the use of pre-vascularised mucosal cell sheets for burn wounds has been rarely evaluated. Therefore, we examined the applicability of an oral pre-vascularised mucosal cell sheet that we had previously developed for the treatment of cutaneous burn wounds. ⋯ The cell sheets had more microvessels and proliferating cells and less neutrophil infiltration and fibrotic features than the controls or skin grafts. The cell sheet induced higher mRNA expression of KRT14, VEGFA, IL10, and AQP3 and lower mRNA expression of TGFB1, IL6, ICAM1, ACTA2, and FN1 than did the controls or skin grafts. Conclusions: The pre-vascularised mucosal cell sheet promotes cutaneous burn wound healing.
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Chronic non-healing wounds represent one of the most common complications of diabetes and need advanced treatment strategies. Exosomes are key mediators of cell paracrine action and can be directly utilized as therapeutic agents for tissue repair and regeneration. Here, we explored the effects of exosomes from human urine-derived stem cells (USC-Exos) on diabetic wound healing and the underlying mechanism. ⋯ Particularly, a pro-angiogenic protein called deleted in malignant brain tumors 1 (DMBT1) was highly expressed in USC-Exos. Further functional assays showed that DMBT1 protein was required for USC-Exos-induced promotion of angiogenic responses of cultured endothelial cells, as well as angiogenesis and wound healing in diabetic mice. Conclusion: Our findings suggest that USC-Exos may represent a promising strategy for diabetic soft tissue wound healing by promoting angiogenesis via transferring DMBT1 protein.
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The application of blood plasma for soft tissue wound healing is receiving much more attention recently. Exosomes are critical paracrine mediators that can be obtained from biological fluids including plasma and be able to induce regenerative effects by transferring bioactive molecules such as microRNAs (miRNAs). This study aimed to investigate the effects of exosomes from human umbilical cord blood plasma (UCB-Exos) on wound healing and to elucidate the underlying mechanism. ⋯ In vitro, UCB-Exos could promote the proliferation and migration of fibroblasts, and enhance the angiogenic activities of endothelial cells. Notably, miR-21-3p was found to be highly enriched in UCB-Exos and served as a critical mediator in UCB-Exos -induced regulatory effects through inhibition of phosphatase and tensin homolog (PTEN) and sprouty homolog 1 (SPRY1). Conclusion: Our results suggest that UCB-Exos are important effectors of plasma activity and can be used as a novel promising strategy for soft tissue wound healing.