RESUMO
Several clinical studies reported that the elevated expression of Chitinase-3-like 1 (CHI3L1) was observed in patients suffering from a wide range of diseases: cancer, metabolic, and neurological diseases. However, the role of CHI3L1 in AD is still unclear. Our previous study demonstrated that 2-({3-[2-(1-Cyclohexen-1-yl)ethyl]-6,7-dimethoxy-4-oxo-3,4-dihydro-2-quinazolinyl}culfanyl)-N-(4-ethylphenyl)butanamide, a CHI3L1 inhibiting compound, alleviates memory and cognitive impairment and inhibits neuroinflammation in AD mouse models. In this study, we studied the detailed correlation of CHI3L1 and AD using serum from AD patients and using CHI3L1 knockout (KO) mice with Aß infusion (300 pmol/day, 14 days). Serum levels of CHI3L1 were significantly elevated in patients with AD compared to normal subjects, and receiver operating characteristic (ROC) analysis data based on serum analysis suggested that CHI3L1 could be a significant diagnostic reference for AD. To reveal the role of CHI3L1 in AD, we investigated the CHI3L1 deficiency effect on memory impairment in Aß-infused mice and microglial BV-2 cells. In CHI3L1 KO mice, Aß infusion resulted in lower levels of memory dysfunction and neuroinflammation compared to that of WT mice. CHI3L1 deficiency selectively inhibited phosphorylation of ERK and IκB as well as inhibition of neuroinflammation-related factors in vivo and in vitro. On the other hand, treatment with recombinant CHI3L1 increased neuroinflammation-related factors and promoted phosphorylation of IκB except for ERK in vitro. Web-based gene network analysis and our results showed that CHI3L1 is closely correlated with PTX3. Moreover, in AD patients, we found that serum levels of PTX3 were correlated with serum levels of CHI3L1 by Spearman correlation analysis. These results suggest that CHI3L1 deficiency could inhibit AD development by blocking the ERK-dependent PTX3 pathway.
Assuntos
Peptídeos beta-Amiloides , Proteína 1 Semelhante à Quitinase-3 , Disfunção Cognitiva , Sistema de Sinalização das MAP Quinases , Camundongos Knockout , Doenças Neuroinflamatórias , Animais , Proteína 1 Semelhante à Quitinase-3/genética , Proteína 1 Semelhante à Quitinase-3/metabolismo , Camundongos , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/genética , Peptídeos beta-Amiloides/metabolismo , Humanos , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/etiologia , Masculino , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteína C-Reativa/metabolismo , Feminino , Doença de Alzheimer/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/tratamento farmacológico , Regulação para Baixo , Modelos Animais de Doenças , Idoso , Camundongos Endogâmicos C57BLRESUMO
Chinese shrimp Fennerpenaeus chinensis (mean length 1.86 ± 0.15 cm, and weight 137.4 ± 12.7 mg) were reared in the different concentrations of bio-floc (control, 60, 80, 100, 120, and 140%) for 90 days. The growth rate was significantly increased over 100% bio-floc concentrations. In the immunological parameters, the gene expression of proPO and lysozyme was considerably increased over 120% bio-floc concentrations. The gene expression of SP was notably elevated at 140% bio-floc concentration. In the antioxidant enzymes, the activity of SOD was considerably decreased over 80% bio-floc concentrations. A notable decline in the activity of CAT was observed over 120% bio-floc concentrations. The results indicate that rearing of Chinese shrimp in bio-floc system can induce the increase of growth performance, enhancement of immune responses, and reduction of oxidative stress.