Background: Microsporum canis is a zoonotic disease that can cause dermatophytosis in animals and humans. Objectives: In clinical practice, ketoconazole (KTZ) and other imidazole drugs are commonly used to treat M. canis infection, but its molecular mechanism is not completely understood.The antifungal mechanism of KTZ needs to be studied in detail. Methods: In this study, one strain of fungi was isolated from a canine suffering with clinical dermatosis and confirmed as M. canis by morphological observation and sequencing analysis.The clinically isolated M. canis was treated with KTZ and transcriptome sequencing was performed to identify differentially expressed genes in M. canis exposed to KTZ compared with those unexposed thereto. Results: At half-inhibitory concentration (½MIC), compared with the control group, 453 genes were significantly up-regulated and 326 genes were significantly down-regulated (p < 0.05). Quantitative reverse transcription polymerase chain reaction analysis verified the transcriptome results of RNA sequencing. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the 3 pathways of RNA polymerase, steroid biosynthesis, and ribosome biogenesis in eukaryotes are closely related to the antifungal mechanism of KTZ. Conclusions The results indicated that KTZ may change cell membrane permeability, destroy the cell wall, and inhibit mitosis and transcriptional regulation through CYP51, SQL, ERG6, ATM, ABCB1, SC, KER33, RPA1, and RNP genes in the 3 pathways. This study provides a new theoretical basis for the effective control of M. canis infection and the effect of KTZ on fungi.

Objective:To explore the effect of oxidative stress on cognitive function following chest blast injury in mice.Methods:Sixty male C57BL/6 mice were divided into control group ( n=15) and chest blast group ( n=45) according to a random number table. The chest blast group was subgrouped at 1, 3, 7 days after injury for subsequent experiments. A self-developed blast injury device was used to prepare the mouse model of chest blast injury. Toklu score was used to evaluate the behavior changes in mice. Morris water maze test was used to evaluate the changes in spatial memory. HE staining was used to observe the pathological changes in the frontal cortex and hippocampus. Tissue reactive oxygen species (ROS) assay kit was used to detect ROS expression in the frontal cortex and hippocampus. Western blotting was used to assess changes of malondialdehyde (MDA) and cyclooxygenase-2 (COX2) in the frontal cortex and hippocampus. Results:The Toklu score of the chest blast group at 1 day after injury was (6.7±2.1)points, significantly higher than that of the control group [(2.0±0.0)points], as well as those of the chest blast group at 3 and 7 days after injury [(2.7±1.2)points and (2.0±0.0)points] (all P<0.01). There was no significant difference in the Toklu score between the control group and the chest blast group at 3 and 7 days after injury (all P>0.05). The Morris water maze test showed that the latency periods at 1 and 3 days after injury were 60.1(60.1, 60.1)seconds and 60.1(56.3, 60.1)seconds, significantly longer than that of the control group [10.1(3.9, 18.3)seconds] (all P<0.01). The latency period of the chest blast group at 7 days after injury was 60.1(30.5, 60.1)seconds, with no difference from the control group ( P>0.05). No significant differences were found in the latency periods of the chest blast group at 1, 3 and 7 days after injury (all P>0.05). In the control group, the pyramidal cells in the frontal cortex and hippocampus were regular in shape, with intensely-stained and clearly visible nuclei as well as uniform cytoplasm. In the chest blast group, diflerent degree of necrosis of pyramidal cells in the frontal cortex and strong cytoplasmic eosinophilia in the hippocampus were observed at different time points after injury. The levels of ROS in the frontal cortex of the chest blast group were (10.43±0.36)RFU/mg and (2.91±0.35)RFU/mg at 3 and 7 days after injury, which were significantly higher than that of the control group [(0.70±0.01)RFU/mg] ( P<0.05 or 0.01). The level of ROS in the frontal cortex of the chest blast group at 3 days after injury was significantly higher than that at 1 day [(2.13±0.65)RFU/mg] and that at 7 days after injury (all P<0.01). There were no statistical differences in the levels of ROS in the frontal cortex of the chest blast group at 1 and 7 days after injury ( P>0.05). The levels of ROS in the hippocampus of the chest blast group were (5.39±0.79)RFU/mg and (5.65±1.17)RFU/mg at 3 and 7 days after injury, which were significantly higher than those of the control group and of the chest blast group at 1 day after injury [ (0.73±0.06)RFU/mg and (2.33±0.02)RFU/mg] (all P<0.01). No significant differences were found between the levels of ROS in the hippocampus of the chest blast group at 3 and 7 days after injury and between the ROS levels of the control group and of the chest blast group at 1 day after injury (all P>0.05). The levels of ROS in the frontal cortex and hippocampus showed significant differences between the chest blast group at 3 and 7 days after injury (all P<0.01) but no significant differences between the control group and the chest blast group at 1 day after injury (all P>0.05). Western blotting showed that the levels of MDA in the frontal cortex of the chest blast group were 0.73±0.04, 0.83±0.04 and 0.99±0.06 at 1, 3 and 7 days after injury, which were significantly higher than that of the control group (0.56±0.04) ( P<0.05 or 0.01). The level of MDA in the frontal cortex of the chest blast group was significantly higher at 7 days after injury compared with that at 1 and 3 days after injury ( P<0.05 or 0.01), but there was no statistical difference between 1 day and 3 days after injury ( P>0.05). The levels of COX2 in the frontal cortex of the chest blast group were 2.93±0.02, 4.82±0.15 and 4.76±0.06 at 1, 3 and 7 days after injury, which were significantly higher than that of the control group (1.93±0.06) (all P<0.01). There were statistical differences in the levels of COX2 in the frontal cortex of the chest blast group at 3 and 7 days after injury compared with that at 1 day after injury (all P<0.01), but no statistical significance was found between 3 and 7 days after injury ( P>0.05). The levels of MDA in the hippocampus of the chest blast group were 0.92±0.11, 0.83±0.03 and 0.68±0.03 at 1, 3 and 7 days after injury, which were significantly higher than that of the control group (0.49±0.03) (all P<0.01). There was a significant difference in the level of MDA in the hippocampus of the chest blast group at 7 days after injury compared with those at 1 and 3 days after injury ( P<0.05 or 0.01), but the difference was not statistically significant among other groups (all P>0.05). The levels of COX2 in the hippocampus of the chest blast group were 0.88±0.06, 0.87±0.06 and 0.80±0.06 at 1, 3 and 7 days after injury, which were significantly higher than that of the control group (0.37±0.04) (all P<0.01). There were significant differences in the levels of COX2 of the chest blast group among 1, 3 and 7 days after injury (all P>0.05). Statistically significant differences were found between the levels of MDA in the frontal cortex and hippocampus of the chest blast group at 1 and 7 days after injury (all P<0.01), but no statistical significant difference between the control group and the chest blast group at 1 day after injury ( P>0.05). The levels of COX2 in the frontal cortex and hippocampus were significantly different among all groups (all P<0.01). Conclusions:In the short term after chest blast injury, there will be cognitive dysfunction in mice. Oxidative stress is one of the important contributing factors, and the cognitive damage in the frontal cortex is more serious than that in the hippocampus.