Translational research : the journal of laboratory and clinical medicine
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Due to soared obesity population worldwide, hepatosteatosis is becoming a major risk factor for hepatocellular carcinoma (HCC). Undertaken molecular events during the progression of steatosis to liver cancer are thus under intensive investigation. In this study, we demonstrated that high-fat diet potentiated mouse liver AKT2. ⋯ Activated AKT2 enhanced the production of monounsaturated fatty acid which was dependent on SREBP1 upregulation of SCD1. Blockage of active SREBP1 and ablation of SCD1 reduced steatosis, inflammation, and tumor burden in DEN-treated Akt2E17K mice. Therefore, AKT2 activation is crucial for the development of steatosis-associated HCC which can be treated with blockage of AKT2-SREBP1-SCD1 signaling cascade.
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Prolonged sevoflurane anesthesia is the primary factor contributing to the development of perioperative neurocognitive disorders (PND). Recent studies have highlighted neuronal apoptosis and abnormal dendritic structures as crucial features of PND. Astrocytes-derived exosomes (ADEs) have been identified as carriers of microRNAs (miRNAs), playing a vital role in cell-to-cell communication through transmitting genetic material. ⋯ Subsequent gain- and loss-of-function experiments were conducted to validate the role of the miR-26a-5p/NCAM axis. Finally, we found that the AKT/GSK3-β/CRMP2 signaling pathway was involved in regulating neurons through exosomal miR-26a-5p. Taken together, our findings suggest that the treatment with miR-26a-5p in ADEs can improve neurocognitive outcomes induced by long-term sevoflurane anesthesia, suggesting a promising approach for retarding the progress of PND.
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Traumatic brain injury (TBI) has a significant impact on cognitive function, affecting millions of people worldwide. Myelin loss is a prominent pathological feature of TBI, while well-functioning myelin is crucial for memory and cognition. Utilizing drug repurposing to identify effective drug candidates for TBI treatment has gained attention. ⋯ In contrast, animals treated with clemastine showed an increase in mature oligodendrocytes, enhanced myelination, and improved performance in the behavioral tests. These preliminary findings support the therapeutic value of clemastine in alleviating TBI-induced cognitive impairment, with substantial clinical translational potential. Our findings also underscore the potential of remyelinating therapies for TBI.
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Transplant centers are currently facing a lack of tools to ensure adequate evaluation of the quality of the available organs, as well as a significant shortage of kidney donors. Therefore, efforts are being made to facilitate the effective use of available organs and expand the donor pool, particularly with expanded criteria donors. Fulfilling a need, we aim to present an innovative analytical method based on solid-phase microextraction (SPME) - chemical biopsy. ⋯ Following metabolomic and lipidomic profiling using high-performance liquid chromatography coupled to a mass spectrometer, we observed differences in the profiles of HBD and DCD kidneys. The alterations were predominantly related to energy and glucose metabolism, and differences in the levels of essential amino acids, purine nucleosides, lysophosphocholines, phosphoethanolamines, and triacylglycerols were noticed. Our results indicate the potential of implementing chemical biopsy in the evaluation of graft quality and monitoring of renal function during perfusion.