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1.
ACS Chem Neurosci ; 13(23): 3291-3302, 2022 12 07.
Article in English | MEDLINE | ID: mdl-36399525

ABSTRACT

Depression is a serious mental illness, mainly characterized as large mood swings and sleep, diet, and cognitive function disorders. NLPR3, one of the inflammasomes that can be activated by a variety of stimuli to promote the maturation and secretion of pro-inflammatory cytokines, has been considered to be involved in the pathophysiology of depression. In this study, the putative role of CY-09, a selective and direct inhibitor of NLRP3, was evaluated in the lipopolysaccharide (LPS)-induced mice. The results of the study indicated that CY-09 significantly decreased the levels of NLRP3 in the hippocampus of LPS-induced mice. In addition, CY-09 increased the sucrose preference and shortened the immobility time in LPS-induced mice, suggesting the antidepressant-like effects of inhibiting NLRP3 inflammasome. Biochemical analysis showed that LPS significantly activated the NLRP3/ASC/cytokine signaling pathway and caused microglial activation, while CY-09 prevented the changes. Moreover, CY-09 increased the brain-derived neurotrophic factor (BDNF) only in microglia but not in the whole hippocampus. Meanwhile, CY-09 did not promote neurogenesis in the hippocampus of LPS mice. In conclusion, the results of the study showed that the antidepressant-like effects of NLRP3 inhibitor CY-09 were mediated by alleviating neuroinflammation in microglia and independent of the neurotrophic function in the hippocampus.


Subject(s)
Depression , Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , Neuroinflammatory Diseases , Thiazolidines , Thiones , Animals , Mice , Inflammasomes/drug effects , Lipopolysaccharides/toxicity , NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitors , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Thiones/pharmacology , Thiones/therapeutic use , Thiazolidines/pharmacology , Thiazolidines/therapeutic use , Neuroinflammatory Diseases/complications , Depression/drug therapy , Depression/etiology , Hippocampus/drug effects , Hippocampus/metabolism
2.
J Invertebr Pathol ; 183: 107625, 2021 07.
Article in English | MEDLINE | ID: mdl-34058216

ABSTRACT

Bombyx mori nucleopolyhedrovirus (BmNPV) is one of the most serious pathogens in sericulture, and the underlying antiviral mechanism in silkworm is still unclear. Bombyx mori Nedd2-like caspase (BmNc) has been identified as a candidate antiviral gene from previous transcriptome data, since it is differentially expressed in the midgut of differentially resistant silkworm strains following BmNPV infection. However, the molecular mechanism by which BmNc responds to BmNPV is unknown. In this study, the relationship between BmNc and BmNPV was confirmed by its significantly different expression in different tissues of differentially resistant strains after BmNPV infection. Moreover, the antiviral role of BmNc was confirmed by the significantly higher fluorescence signals of BV-eGFP after knockdown of BmNc in BmN cells, and a reduced signal after overexpression. This was further verified by the capsid gene vp39 expression, DNA copy number, and GP64 protein level in the RNAi and overexpression groups. Furthermore, the antiviral phenomenon of BmNc was found to be associated with apoptosis. In brief, BmNc showed a relatively high expression level in the metamorphosis stages, and the effect of BmNc on BmNPV infection following RNAi and overexpression was eliminated after treatment with the inducer, Silvestrol, and the inhibitor, Z-DEVD-FMK, respectively. Therefore, it is reasonable to conclude that BmNc is involved in anti-BmNPV infection via the mitochondrial apoptosis pathway. The results provide valuable information for elucidating the molecular mechanism of silkworm resistance to BmNPV infection.


Subject(s)
Bombyx/genetics , Bombyx/virology , Caspases/genetics , Drosophila Proteins/genetics , Nucleopolyhedroviruses/physiology , Animals , Bombyx/enzymology , Bombyx/growth & development , Caspases/metabolism , Drosophila Proteins/metabolism , Larva/growth & development , Larva/virology
3.
J Hazard Mater ; 365: 196-204, 2019 03 05.
Article in English | MEDLINE | ID: mdl-30439619

ABSTRACT

The high-efficiency capture of Tobacco Specific Nitrosamines by Hß zeolite in solution is reported for the first time, along with the adsorption of 4-methylnitrosamino-1-3-pyridyl-1-butanone in aqueous solution. Different from other zeolites such as NaZSM-5, the specific pore size of Hß exerted a crucial function endowing the zeolite a higher removal of TSNA and selectivity of NNK. The adsorption thermodynamics of NNK by Hß in aqueous adsorption was fitted to Temkin adsorption model with a linearly decreasing isosteric heat of adsorption. In addition, the adsorptive capacity of Hß zeolite for NNK reached over 70 mg g-1, offering a powerful sorbent of TSNA to protect environment.


Subject(s)
Carcinogens/chemistry , Nicotiana/chemistry , Nitrosamines/chemistry , Zeolites/chemistry , Adsorption , Solutions , Thermodynamics
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