1.Liquiritin improves depressive behavior in rats with post-stroke depression by reducing apoptosis of amygdala cells
Fengfeng XU ; Da XU ; Hanxiao ZHU ; Riwei OUYANG ; Ning RONG ; Changqin XU ; Yun LI
International Journal of Cerebrovascular Diseases 2021;29(4):277-284
Objective:To investigate the effect of liquiritin on the apoptosis of amygdala cell and the expression of apoptosis-related factors Bax and Bcl-2 protein in rats with post-stroke depression (PSD).Methods:Sixty rats were randomly divided into normal control group, stroke group, PSD group, citalopram group, liquiritin group, and normal saline control group ( n=10 in each group). The middle cerebral artery was occluded with a suture method to induce focal cerebral ischemia, and the PSD model was established by chronic and unpredictable mild stress stimulation and orphanism. At the same time every week after the model was made, the weight of rats in each group was measured and the depression behavior was evaluated, including sucrose water test and open field test. At 6 weeks after the model was made, TUNEL staining was used to detect the apoptosis of amygdala cell, immunofluorescence staining was used to detect the expression of Bax and Bcl-2 in the amygdala, and Western blot analysis was used to detect the protein expression of Bax and Bcl-2 in the amygdala. Results:Compared with the liquiritin group, citalopram group and normal control group, the body weight and sucrose solution preference of rats in the stroke group, PSD group and normal saline control group were decreased, and the horizontal and vertical movements in open field test were decreased; the differences were statistically significant (all P<0.01). TUNEL staining results showed that compared with the liquiritin group, citalopram group and normal control group, the number of apoptotic cells was significantly increased in the stroke group, PSD group, and normal saline control group; the difference was statistically significant (all P<0.01). The results of immunofluorescence staining showed that compared with the liquiritin group, citalopram group and normal control group, the number of bcl-2 immunoreactive cells in amygdala of the stroke group, PSD group and normal saline control group was significantly decreased, while the number of Bax immunoreactive cells was significantly increased; the difference was statistically significant (all P<0.01). Western blot analysis showed that compared with the liquiritin group and citalopram group, the expression of bcl 2 protein in amygdala of the stroke group, PSD group and normal saline control group was significantly decreased, while the expression of Bax protein was significantly increased; the difference was statistically significant (all P<0.01). Conclusion:Liquiritin can alleviate the symptoms of PSD, and its mechanism may be related to inhibiting the apoptosis of amygdala cells and regulating the expression of apoptosis-related factors.
2.Mechanism of axonal transport dysfuction of mitochondria in Alzheimer's disease
Yihan SHEN ; Hanxiao XU ; Linhao JIANG ; Minhui XU ; Tianjiao XIA
Chinese Journal of Neuromedicine 2023;22(5):476-479
Alzheimer's disease (AD) is a central neurodegenerative disease with still unclear pathogenesis. Recent studies have shown that axonal transport dysfuction of mitochondria may contribute to AD progression. Normal mitochondrial axonal transport mainly involves microtubules, molecular motors and connexins, while AD early pathological changes can damage mitochondrial axonal transport by interfering with these proteins: accumulated β-amyloid (Aβ) impairs the function of molecular motors; abnormally modified Tau protein reduces microtubule stability; mutant presenilin-1 (PS1) can induce phosphorylation of some related proteins by activating glycogen synthase kinase-3β (GSK-3β); all these processes can damage mitochondrial axonal transport, leading to synaptic dysfunction. This review aims to clarify the possible mechanisms of axonal transport dysfuction of mitochondria in AD and provides new ideas for AD treatment.
3.In silico investigation of agonist activity of a structurally diverse set of drugs to hPXR using HM-BSM and HM-PNN.
Yi-Ming ZHANG ; Mei-Jia CHANG ; Xu-Shu YANG ; Xiao HAN
Journal of Huazhong University of Science and Technology (Medical Sciences) 2016;36(3):463-468
The human pregnane X receptor (hPXR) plays a critical role in the metabolism, transport and clearance of xenobiotics in the liver and intestine. The hPXR can be activated by a structurally diverse of drugs to initiate clinically relevant drug-drug interactions. In this article, in silico investigation was performed on a structurally diverse set of drugs to identify critical structural features greatly related to their agonist activity towards hPXR. Heuristic method (HM)-Best Subset Modeling (BSM) and HM-Polynomial Neural Networks (PNN) were utilized to develop the linear and non-linear quantitative structure-activity relationship models. The applicability domain (AD) of the models was assessed by Williams plot. Statistically reliable models with good predictive power and explain were achieved (for HM-BSM, r (2)=0.881, q LOO (2) =0.797, q EXT (2) =0.674; for HM-PNN, r (2)=0.882, q LOO (2) =0.856, q EXT (2) =0.655). The developed models indicated that molecular aromatic and electric property, molecular weight and complexity may govern agonist activity of a structurally diverse set of drugs to hPXR.
Computer Simulation
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Humans
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Models, Statistical
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Molecular Weight
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Neural Networks (Computer)
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Quantitative Structure-Activity Relationship
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Receptors, Steroid
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agonists
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chemistry
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Small Molecule Libraries
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chemistry
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Static Electricity
4. Incidence and risk factors of peripartum mood disorder: a prospective cohort study
Hanxiao ZUO ; Xiaohong XU ; Chunyan REN ; Mingming CUI ; Dongming HUANG ; Rong MI ; Li LI ; Qingyong XIU ; Yanyu LYU
Chinese Journal of Perinatal Medicine 2019;22(12):859-866
Objective:
To investigate the incidence and risk factors of peripartum mood disorder (PPMD) in order to improve clinical prevention and intervention of this condition.
Methods:
This was a prospective cohort study recruiting first-trimester pregnant women (<13 gestational weeks) from Beijing Daxing Maternal and Child Care Hospital from October 1, 2016 to December 31, 2017. Zung Self-rating Anxiety Scale (SAS) and Zung Self-rating Depression Scale (SDS) were used to evaluate the anxiety and depression status in the second and third trimesters, respectively. Their life styles, social and environmental factors exposure during pregnancy were also collected. Statistical analysis was conducted using