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IntroductionViral diseases have always been intricate and persistent issues throughout the world and there is a lack of holistic discoveries regarding the molecular dysregulations of virus-host interactions. The temporal proteomics strategy can identify various differentially expressed proteins and offer collaborated interaction networks under pathological conditions.MethodHerein, temporal proteomics at various hours post infection of Vero cells were launched to uncover molecular alternations during vaccinia virus (VACV)-induced cell migration. Different stages of infection were included to differentiate gene ontologies and critical pathways at specific time points of infection via bioinformatics.ResultsBioinformatic results showed functional and distinct ontologies and pathways at different stages of virus infection. The enrichment of interaction networks and pathways verified the significances of the regulation of actin cytoskeleton and lamellipodia during VACV-induced fast cell motility.DiscussionThe current results offer a systematic proteomic profiling of molecular dysregulations at different stages of VACV infection and potential biomedical targets for treating viral diseases.

The mitochondrial permeability transition pore is a nonspecific transmembrane channel. Inhibition of mitochondrial permeability transition pore opening has been shown to alleviate mitochondrial swelling, calcium overload, and axonal degeneration. Cyclophilin D is an important component of the mitochondrial permeability transition pore. Whether cyclophilin D participates in mitochondrial impairment and axonal injury after intracerebral hemorrhage is not clear. In this study, we established mouse models of intracerebral hemorrhage in vivo by injection of autologous blood and oxyhemoglobin into the striatum in Thy1-YFP mice, in which pyramidal neurons and axons express yellow fluorescent protein. We also simulated intracerebral hemorrhage in vitro in PC12 cells using oxyhemoglobin. We found that axonal degeneration in the early stage of intracerebral hemorrhage depended on mitochondrial swelling induced by cyclophilin D activation and mitochondrial permeability transition pore opening. We further investigated the mechanism underlying the role of cyclophilin D in mouse models and PC12 cell models of intracerebral hemorrhage. We found that both cyclosporin A inhibition and short hairpin RNA interference of cyclophilin D reduced mitochondrial permeability transition pore opening and mitochondrial injury. In addition, inhibition of cyclophilin D and mitochondrial permeability transition pore opening protected corticospinal tract integrity and alleviated motor dysfunction caused by intracerebral hemorrhage. Our findings suggest that cyclophilin D is used as a key mediator of axonal degeneration after intracerebral hemorrhage; inhibition of cyclophilin D expression can protect mitochondrial structure and function and further alleviate corticospinal tract injury and motor dysfunction after intracerebral hemorrhage. Our findings provide a therapeutic target for preventing axonal degeneration of white matter injury and subsequent functional impairment in central nervous diseases.