The immune response mechanism of Nilaparvata lugens against a combined infection of rice ragged stunt virus and Metarhizium anisopliae.

BACKGROUND: Previous studies of brown planthopper (BPH), Nilaparvata lugens, showed that carrying the plant pathogenic virus, rice ragged stunt virus (RRSV), enhanced the lethality of the entomopathogenic fungus, Metarhizium anisopliae (YTTR). The underlying mechanism for this was not established but a serine protease cascade was hypothesized to be involved. RESULTS: Two immune response genes, NlKPI and NlVenomase, were identified and shown to be involved. The synthesized double-strand RNA (dsRNA) techniques used in this study to explore gene function revealed that treatment with dsRNA to silence either gene led to a higher BPH mortality from M. anisopliae infection than the dsRNA control treatment. NlKPI and NlVenomase play vital roles in BPH immunity to defend against alien pathogens. Both genes participate in the immune response process of BPH against co-infection with RRSV and M. anisopliae YTTR by regulating the expression of antimicrobial peptides and phenoloxidase activity. CONCLUSION: Our study provided new targets for BPH biocontrol and laid a solid foundation for further research on the interaction of virus-insect-EPF (entomopathogenic fungus). © 2023 Society of Chemical Industry.

Nano-CuO causes cell damage through activation of dose-dependent autophagy and mitochondrial lncCyt b-AS/ND5-AS/ND6-AS in SH-SY5Y cells.

Metal copper oxide nanoparticles (nano-CuO) are under mass production and have been widely utilized in many fields including catalysis, gas sensors, semiconductor materials, etc. The broad applications of nano-CuO have increased the possibility of risk to incidental exposure to the environment, and therefore, an in-depth investigation of their effects on live cells is required. This study investigated the impact of the nano-CuO on SH-SY5Y cells, and findings showed that the ratio of LC3-II/LC3-I was significantly increased in SH-SY5Y cells when the cells were treated with nano-CuO. However, if the autophagy inhibitor Bafilomycin A1 (Baf A1) was co-treated, the ratio of LC3-II/LC3-I was further improved. These outcomes might indicate that autophagy flux was permanently elevated by adding nano-CuO. Further results found highly activated levels of long noncoding RNAs (lncRNAs) under nano-CuO treatment. The data illustrate a mechanism that nano-CuO can promote autophagy and activate lncCyt b-AS/ND5-AS/ND6-AS in SH-SY5Y cells and have critical implications for nanoparticle biomedical applications.

Asparagine endopeptidase deletion ameliorates cognitive impairments by inhibiting proinflammatory microglial activation in MPTP mouse model of Parkinson disease.

In addition to motor dysfunction, cognitive impairments have been reported to occur in patients with early-stage Parkinson's disease (PD). In this study, we examined a PD mouse model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This treatment led to the degeneration of nigrostriatal dopaminergic neurons in mice, a phenomenon that is consistent with previous studies. Besides, spatial memory and object recognition of MPTP-treated mice were impaired, as denoted by the Morris water maze (MWM) and novel object recognition (NOR) tests, respectively. Moreover, hippocampal synaptic plasticity (long-term potentiation and depotentiation) and the levels of synaptic proteins in hippocampus were decreased after MPTP treatment. We also found that MPTP resulted in the microglial activation and an inflammatory response in the striatum and hippocampus. Mammalian asparagine endopeptidase (AEP), a cysteine lysosomal protease, is involved in the cleavage and activation of Toll-like receptors (TLRs). The deletion of AEP can inhibit TLR4 in a mouse model of Alzheimer's disease, and TLR4 is upregulated in PD, inducing microglial activation and inflammation. We found that AEP deletion provided greater resistance to the toxic effects of MPTP. AEP knockout ameliorated the cognition and the synaptic plasticity defects in the hippocampus. Furthermore, AEP deletion decreased the expression of TLR4 and reduced microglial activation and the levels of several proinflammatory cytokines. Thus, we suggest that AEP plays a role in the inflammation induced by MPTP, and TLR4 might also involve in this process. AEP deletion could be a possible treatment strategy for the cognitive deficits of PD.

Legumain knockout improved cognitive impairment via reducing neuroinflammation in right unilateral common carotid artery occlusion mice.

AIMS: Chronic cerebral hypoperfusion (CCH) is a state of chronic cerebral blood flow reduction, and it is the main cause of cognitive impairment and neurodegenerative diseases. The abnormal upregulation of legumain, a lysosomal cysteine protease, trigger synaptic plasticity impairment and neuroinflammation, which are involved in the underlying pathophysiology of CCH. At present, few studies have reported the role of legumain in cognitive impairment caused by CCH. In our study, we aimed to investigate the involvement of legumain knockout in cognitive function and neuroinflammation in a CCH mouse model. MAIN METHODS: In this study, right unilateral common carotid artery occlusion (rUCCAO) was used to simulate the pathological state of cerebral ischemic injury. Various behavioural tests were executed to assess cognitive performance. In vivo electrophysiological recordings were used to measure synaptic functions. Western blotting, Golgi staining, haematoxylin/eosin staining, and immunofluorescence assays were conducted to examine pathological changes and molecular mechanisms. KEY FINDINGS: The data showed that the level of legumain was significantly increased in the hippocampus of mice subjected to rUCCAO. Legumain knockout significantly improved cognitive function and synaptic plasticity induced by rUCCAO, suggesting that legumain knockout-regulation effectively protected against CCH-induced behavioural dysfunctions. Moreover, legumain knockout suppressed rUCCAO-induced microglial activation, reduced the abnormal expression of inflammatory cytokines and the inflammasome complex, and impeded the activation of P65 and pyroptosis. SIGNIFICANCE: These findings suggest that legumain is an effective regulator of CCH, and may be an ideal target for the development of cerebral ischemia treatments in the future.

Legumain knockout improves repeated corticosterone injection-induced depression-like emotional and cognitive deficits.

Emotional and cognitive impairment has been recognized as a central feature of depression, which is closely related to hyperfunction of the hypothalamic-pituitary-adrenal (HPA) axis caused by down-regulation of glucocorticoid receptor (GR) expression in patients. A decrease in GR expression can cause pathological changes and lead to the impairment of synaptic plasticity. Legumain, a lysosomal cysteine protease, plays an important role in neurological diseases. It is reported that legumain activates the MAPK signaling pathway, which modifies the GR. Therefore, we hypothesize that regulation of the GR by legumain plays a crucial role in the pathological process of depression. The relationships between legumain, GR, synaptic plasticity and emotional and cognitive deficits were explored in this study. The results demonstrated that repeated corticosterone (CORT) injections (3 weeks) induced emotional and cognitive deficits in mice, based on behavioral experiments and the detection of synaptic plasticity. Furthermore, CORT injections decreased the expression of hippocampal synapse-related proteins, cell density and dendritic spine density in the hippocampus, accompanied by increased protein expression in the MAPK signaling pathway and decreased expression of the GR. In conclusion, our results demonstrated that legumain knockout up-regulated expression of the GR by reducing protein expression in the MAPK signaling pathway, thereby improving hippocampal synaptic plasticity as well as the emotional and cognitive impairment of model mice. This suggests that legumain may be an effective therapeutic target for emotional and cognitive deficits.