The current severe situation of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not been reversed and posed great threats to global health. Therefore, there is an urgent need to find out effective antiviral drugs. The 3-chymotrypsin-like protease (3CLpro) in SARS-CoV-2 serve as a promising anti-virus target due to its essential role in the regulation of virus reproduction. Here, we report an improved integrated approach to identify effective 3CLpro inhibitors from effective Chinese herbal formulas. With this approach, we identified the 5 natural products (NPs) including narcissoside, kaempferol-3-O-gentiobioside, rutin, vicenin-2 and isoschaftoside as potential anti-SARS-CoV-2 candidates. Subsequent molecular dynamics simulation additionally revealed that these molecules can be tightly bound to 3CLpro and confirmed effectiveness against COVID-19. Moreover, kaempferol-3-o-gentiobioside, vicenin-2 and isoschaftoside were first reported to have SARS-CoV-2 3CLpro inhibitory activity. In summary, this optimized integrated strategy for drug screening can be utilized in the discovery of antiviral drugs to achieve rapid acquisition of drugs with specific effects on antiviral targets.
Objective:The present study was designed to explore the long-term differences between three mouse models for depression.
Method:In the present study, the unpredictable chronic mild stress (UCMS) model, the glucocorticoid/corticosterone model, and the olfactory bulbectomy model were compared at two, three, and five weeks after model induction. Behavioral testing performed included forced-swimming, tail suspension, open-field and elevated plusmaze tests. In addition, 5-hydroxytryptamine (5-HT) and dopamine levels, and mRNA and protein expressions related to 5-HT synthesis, transport, and signaling were analyzed in the hippocampus of tested animals.
Results:Our results revealed that each model demonstrated a specific profile of markers, whereas the stability of them differed over testing time.
Conclusions:Each model provided a unique set of advantages that can be considered depending on the context and aims of each study. Among the three models, the UCMS model was mostly stable and appeared to the best model for testing long-term depression-like state. K E Y W O R D S 5-HT, corticosterone, depression model, glucocorticoid, olfactory bulbectomy, UCMS How to cite this article: Zhu H, Tao Y, Wang T, et al. Long-term stability and characteristics of behavioral, biochemical, and molecular markers of three different rodent models for depression. Brain Behav. 2020;10:e01508. https ://doi.
Objective:
The aim of the present study is to determine whether plasma bile acids (BAs) could be used as an auxiliary diagnostic biomarker to distinguish patients with schizophrenia from healthy controls.
Methods:
Seventeen different BAs were quantitatively measured in plasma of 12 healthy participants and 12 patients with schizophrenia. Then, the data were subjected to correlation and linear discriminant analysis (LDA).
Results:
The concentrations of cholic acid (CA), taurochenodeoxycholic acid (TCDCA) and taurodeoxycholic acid (TDCA) were significantly decreased in plasma of the schizophrenia patients. Correlation analysis showed the concentrations of CA, TCDCA and TDCA were negatively correlated with schizophrenia. In addition, LDA demonstrated that combination of CA, TCDCA and TDCA with a classification formula could predict correctly classified cases and the accuracy of prediction was up to 95.83 %.
Conclusion:
Combination of the three BAs may be useful to diagnose schizophrenia in plasma samples.
Background: Hyodeoxycholic acid (HDCA) is a natural secondary bile acid with enormous pharmacological effects, such as modulating inflammation in neuron. However, whether HDCA could suppress microglial inflammation has not been elucidated yet. Aims: To determine the anti-microglial inflammatory effect of HDCA in lipopolysaccharide (LPS) models and its mechanisms. Methods: The effect of HDCA was evaluated in LPS-stimulated BV2 microglial cells in vitro and the cortex of LPS-treated mice in vivo. Immunohistochemistry and immunofluorescence were used to visualize the localization of nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) and ionized calcium-binding adaptor protein-1 (Iba-1), respectively. The mRNA expression of inflammatory cytokines was measured by RT-qPCR. The protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), takeda G-coupled protein receptor 5 (TGR5), and the phosphorylation of protein kinase B (AKT), NF-κB, and inhibitor of NF-κB protein α (IκBα) was examined by Western blot. Results: HDCA inhibited the inflammatory responses in LPS-treated BV2 cells and in the cortex of LPS-treated mice, evidenced by decreased production of inflammatory mediators such as iNOS, COX-2, tumor necrosis factor (TNF-α), interleukin (IL)-6, and IL-1β. Further study demonstrated that HDCA repressed the phosphorylation, nuclear translocation, and transcriptional activity of NF-κB and inhibited the activation of AKT in BV-2 cells induced by LPS. Meanwhile, addition of TGR5 inhibitor, triamterene, abolished the effects of HDCA on TGR5, AKT, and NF-κB. Conclusion: The present study demonstrated that HDCA prevents LPS-induced microglial inflammation in vitro and in vivo, the action of which is via regulating TGR5/AKT/NF-κB signaling pathway.
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