Int J Med Sci
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Background: Acute myeloid leukemia (AML) is a malignant hematological disease with high refractory rate. Immune escape of AML cells is one of the underlying mechanisms mediating the relapse of the cancers. Various immunotherapies based on the 'patients' immune response to tumor cells have been developed to targeting the immune escape of AML cells, which lead to the minimal residual disease (MRD) after treatment. ⋯ SZU-106-DAC-AML, constructed by conjugating SZU-106 to DAC treated tumor cells, exhibited increased expression of tumor antigens, and enhanced the activation of DC cells and T cells in vitro and in vivo. The result of xenograft tumor model showed that SZU-106-DAC-AML tumor vaccine greatly inhibited tumor growth and prolonged animal survival. Conclusions: Conjugation of TLR7 agonist combined with up-regulation of tumor antigen expression improved the effectiveness of whole-cell tumor vaccine in AML.
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Reconstruction of bone defects is one of the most substantial and difficult clinical challenges in orthopedics. Transforming growth factor beta 1 (TGFβ1) might play an important role in stimulating osteogenic differentiation of bone morphogenetic protein 9 (BMP9)-induced C3H10T1/2 mesenchymal stem cells. In our current study, we examined the potential synergy between TGFβ1 and BMP9 in promoting the osteogenesis of C3H10T1/2 cells, and whether such effects could contribute to bone formation in vivo. ⋯ Subsequent mechanistic studies found that TGFβ1-induced enhancement of osteogenesis in BMP9-overexpressing C3H10T1/2 cells was accompanied by augmented expression of heat shock protein 47 (HSP47), a collagen-specific molecular chaperone essential for collagen biosynthesis, and can be attenuated by pirfenidone, a known anti-fibrotic inhibitor. Interestingly, protein microarray analysis suggested that TGFβ1/BMP9-dependent osteogenesis of C3H10T1/2 cells seemed to involve several non-canonical signaling pathways such as Janus kinase-signal transducer and activator of transcription, phosphoinositide-3-kinase-protein kinase B, and mitogen-activated protein kinase. These results provided further evidence that TGFβ1 could promote bone formation from BMP9-induced C3H10T1/2 cells and shed important light on the underlying molecular mechanisms.
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Background: Hemorrhagic shock-induced ischemia and hypoxia elicit endoplasmic reticulum stress (ERS) that leads to cell apoptosis, tissue structural damage and organ dysfunction and failure. Stellate ganglion blockade (SGB) has been demonstrated to improve intestinal barrier dysfunction induced by hemorrhagic shock. The present study sought to investigate whether the beneficial effect of SGB on the intestinal mucosal barrier function is via suppression of ERS. ⋯ Results: Either SGB or administration of ERS inhibitor, 4-PBA, alleviated hemorrhagic shock-induced adverse effects such as intestinal mucosal barrier dysfunction and excessive autophagy, which were characterized by damaged intestinal tissue, enhanced intestinal permeability and D-LA and I-FABP levels in plasma, and increased expressions of ATF6α, PERK, IRE1α in intestinal tissue. In contrast, administration of ERS agonist, TM, suppressed the beneficial effects of SGB on intestinal tissue and function during hemorrhagic shock. Conclusion: The SGB repairs intestinal mucosal barrier through suppression of ERS following hemorrhagic shock.
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Aging is the most important current issue and is usually accompanied by complications, such as cardiovascular disorders and neurodegenerative diseases, which are the leading causes of death worldwide and the second major cause of death in Taiwan. In this study, we have investigated the protective effect of adipose-derived mesenchymal stem cells (ADSCs) and the role of epigallocatechin gallate (EGCG) in enhancing this effect in aging cerebral cortex of rats. Further, we attempted to elucidate the molecular mechanism through which EGCG influences the protective effects of ADSC. ⋯ Moreover, it increased the available brain-derived neurotrophic factor to a higher degree than that in the ADSC group. Furthermore, western blotting showed that EGCG improved the antioxidant activity of the ADSCs in the cortex tissues via the Nrf-2 and HO-1 pathway. Based on these findings, we propose that this variation in stem cell treatment may facilitate functional recovery and enhanced neuroprotection in aged brains.
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Tert-butylhydroquinone (tBHQ) is an antioxidant compound that exhibits cytoprotective effect in many tissues under pathological condition. However, its role in carbon tetrachloride (CCL4) induced liver injury is still unclear. Here we established a carbon tetrachloride induced hepatic injury model in mice to determine whether tBHQ can mitigate CCL4 induced liver damage. ⋯ Moreover, tBHQ mitigated apoptosis of hepatocytes, oxidative stress and lipid peroxidation in vivo and in vitro. We also found the possible mechanism of protective effects of tBHQ was associated with activation of Nrf2/ heme oxygenase-1 (HO-1) pathway. In conclusion, our study revealed tBHQ can be a potential therapeutic drug in treatment of acute hepatic injury.