ObjectiveTo investigate the role of 4-week high-intensity interval training (HIIT) in modulating the metabolic homeostasis of the pyruvate-lactate axis in the hippocampus of rats with chronic unpredictable mild stress (CUMS) to improve their depressive-like behavior. MethodsForty-eight SPF-grade 8-week-old male SD rats were randomly divided into 4 groups: the normal quiet group (C), the CUMS quiet group (M), the normal exercise group (HC), and the CUMS exercise group (HM). The M and HM groups received 8 weeks of CUMS modeling, while the HC and HM groups were exposed to 4 weeks of HIIT starting from the 5th week (3 min (85%-90%) S_max+1 min (50%-55%) S_max, 3-5 cycles, S_max is the maximum movement speed). A lactate analyzer was used to detect the blood lactate concentration in the quiet state of rats in the HC and HM groups at week 4 and in the 0, 2, 4, 8, 12, and 24 h after exercise, as well as in the quiet state of rats in each group at week 8. Behavioral indexes such as sucrose preference rate, number of times of uprightness and number of traversing frames in the absenteeism experiment, and other behavioral indexes were used to assess the depressive-like behavior of the rats at week 4 and week 8. The rats were anesthetized on the next day after the behavioral test in week 8, and hippocampal tissues were taken for assay. LC-MS non-targeted metabolomics, target quantification, ELISA and Western blot were used to detect the changes in metabolite content, lactate and pyruvate concentration, the content of key metabolic enzymes in the pyruvate-lactate axis, and the protein expression levels of monocarboxylate transporters (MCTs). Results4-week HIIT intervention significantly increased the sucrose preference rate, the number of uprights and the number of traversed frames in the absent field experiment in CUMS rats; non-targeted metabolomics assay found that 21 metabolites were significantly changed in group M compared to group C, and 14 and 11 differential metabolites were significantly dialed back in the HC and HM groups, respectively, after the 4-week HIIT intervention; the quantitative results of the targeting showed that, compared to group C, lactate concentration in the hippocampal tissues of M group, compared with group C, lactate concentration in hippocampal tissue was significantly reduced and pyruvate concentration was significantly increased, and 4-week HIIT intervention significantly increased the concentration of lactate and pyruvate in hippocampal tissue of HM group; the trend of changes in blood lactate concentration was consistent with the change in lactate concentration in hippocampal tissue; compared with group C, the LDHB content of group M was significantly increased, the content of PKM2 and PDH, as well as the protein expression level of MCT2 and MCT4 were significantly reduced. The 4-week HIIT intervention upregulated the PKM2 and PDH content as well as the protein expression levels of MCT2 and MCT4 in the HM group. ConclusionThe 4-week HIIT intervention upregulated blood lactate concentration and PKM2 and PDH metabolizing enzymes in hippocampal tissues of CUMS rats, and upregulated the expression of MCT2 and MCT4 transport carrier proteins to promote central lactate uptake and utilization, which regulated metabolic homeostasis of the pyruvate-lactate axis and improved depressive-like behaviors.

ObjectiveThis study aimed to investigate the effects of 4-week high-intensity interval training (HIIT) on synaptic plasticity in the prefrontal cortex (PFC) of rats exposed to chronic unpredictable mild stress (CUMS), and to explore its potential mechanisms. MethodsA total of 48 male Sprague-Dawley rats were randomly divided into 4 groups: control (C), model (M), control plus HIIT (HC), and model plus HIIT (HM). Rats in groups M and HM underwent 8 weeks of CUMS to establish depression-like behaviors, while groups HC and HM received HIIT intervention beginning from the 5th week for 4 consecutive weeks. The HIIT protocol consisted of repeated intervals of 3 min at high speed (85%-90% maximal training speed, S_max) alternated with one minute at low speed (50%-55% S_max), with 3 to 5 sets per session, conducted 5 d per week. Behavioral assessments and tail-vein blood lactate levels were measured at the end of the 4th and 8th weeks. After the intervention, rat PFC tissues were collected for Golgi staining to analyze synaptic morphology. Enzyme-linked immunosorbent assays (ELISA) were employed to detect brain-derived neurotrophic factor (BDNF), monocarboxylate transporter 1 (MCT1), lactate, and glutamate levels in the PFC, as well as serotonin (5-HT) levels in serum. Additionally, Western blot analysis was conducted to quantify the expression of synaptic plasticity-related proteins, including c-Fos, activity-regulated cytoskeleton-associated protein (Arc), and N-methyl-D-aspartate receptor 1 (NMDAR1). ResultsCompared to the control group (C), the CUMS-exposed rats (group M) exhibited significant reductions in sucrose preference rates, number of grid crossings, frequency of upright postures, and entries into and duration spent in open arms of the elevated plus maze, indicating marked depressive-like behaviors. Additionally, the group M showed significantly reduced dendritic spine density in the PFC, along with elevated levels of c-Fos, Arc, NMDAR1 protein expression, and increased concentrations of lactate and glutamate. Conversely, BDNF and MCT1 contents in the PFC and 5-HT levels in serum were significantly decreased. Following HIIT intervention, rats in the group HM displayed considerable improvement in behavioral indicators compared with the group M, accompanied by significant elevations in PFC MCT1 and lactate concentrations. Furthermore, HIIT notably normalized the expression levels of c-Fos, Arc, NMDAR1, as well as glutamate and BDNF contents in the PFC. Synaptic spine density also exhibited significant recovery. ConclusionFour weeks of HIIT intervention may alleviate depressive-like behaviors in CUMS rats by increasing lactate levels and reducing glutamate concentration in the PFC, thereby downregulating the overexpression of NMDAR, attenuating excitotoxicity, and enhancing synaptic plasticity.

Objective To explore the influence of extracellular matrix protein ABI-interactor 3-binding protein(ABI3BP)on vesicular stomatitis virus(VSV)genome replication and innate immune signaling pathway. Methods The small interfering RNA(siRNA)was transfected to knock down ABI3BP gene in human skin fibroblast BJ-5ta cells.VSV-green fluorescent protein(VSV-GFP)-infected cell model was established.The morphological changes and F-actin stress fiber formation were detected on ABI3BP knockdown cells by phalloidin immunofluorescence staining.The mRNA level of virus replication was detected by RT-qPCR in BJ-5ta cells after VSV-GFP infection;western blotting was performed to detect the changes in interferon regulatory factor 3(IRF3)andTANK-binding kinase 1(TBK1)phosphorylation levels. Results The VSV-GFP-infected BJ-5ta cell model was successfully established.Efficient knockdown of ABI3BP in BJ-5ta cells was achieved.Phalloidin immunofluorescence staining revealed structural rearrangement of intracellular F-actin after ABI3BP gene knockdown.Compared with the control group,the gene copy number of VSV-GFP in ABI3BP knockdown cells increased by 2.2-3.5 times(P＜0.01)and 2.2-4.0 times(P＜0.01)respectively when infected with VSV of multiplicity of infection 0.1 and 1.The expression of viral protein significantly increased in ABI3BP knockdown cells after virus infection.The activation of type-Ⅰ interferon pathway,as determined by phosphorylated IRF3 and phosphorylated TBK1,was significantly decreased in ABI3BP knockdown cells after VSV-GFP infection. Conclusions Extracellular matrix protein ABI3BP plays an important role in maintaining the formation and rearrangement of actin structure.ABI3BP gene deletion promotes RNA virus replication,and ABI3BP is an important molecule that maintains the integrity of type Ⅰ interferon pathway.

The incidence rate of depression is increasing, but its pathological mechanism is still unknown. More evidence shows that the occurrence and development of depression is closely related to the changes of gut microbiome. However, due to the huge differences in bacterial composition among individuals caused by different environmental factors, researchers usually need a large number of samples to get reliable results. Experimental animal models play an important role in the pathogenesis of diseases and the mechanism of drug action because of their highly consistent background, controllable experimental environment, and the characteristics of artificial intervention. Therefore, the selection of appropriate experimental animal models can not only simulate the clinical symptoms of human depression, but also reveal the causal relationship between clinical characteristics and gut microbiome changes. In this review, the development and application of fecal microbiota transplantation technology, the close relationship between flora and depression, the application of humanized fecal microbiota transplantation experimental animal model in the study of depression, as well as the preparation methods and key technologies of humanized fecal microbiota were summarized, which provided a reference for the research on the pathogenesis of depression and the mechanism of antidepressant drugs of humanized fecal microbiota transplantation experimental animal model. This review provides a reference for the reasonable application of this aspect.

Objective To evaluate the effects of antiretroviral therapy(ART)for the prevention of mother-to-child transmission(PMTCT)of acquired immune deficiency syndrome(AIDS)on the growth and development of 18-month-old children born by human immunodeficiency virus(HIV)-positive pregnant women in Lingshan County,Guangxi Zhuang Autonomous Region,and provide scientific evidence for improving the ART medication plan for PMTCT.Methods Lingshan County,ranking the first in the HIV-epidemic counties of Guangxi,was selected as the research site.According to the design of retrospective case-control study,we assigned all the subjects into the case group and the control group:(1)The case group included the HIV-positive pregnant women who had received ART for PMTCT and their HIV-negative infants in Lingshan County from 2010 to 2017.The historical cards and PMTCT data of them were collected from the national PMTCT database.(2)The control group included the healthy pregnant women and their healthy babies born in the Lingshan Maternity and Infant Hospital in 2017,and the children's growth and development data were collected.The stunted growth in children was defined as at least one of the three main indicators of body height,body weight,and head circumference below the normal range.Results The number of HIV-positive mothers and their infants in the case group was 391 and 368,respectively,and 87.21%(341/391)and 95.38%(351/368)of mothers and infants respectively received ART medication.The HIV positive rate,mortality rate,and mother-to-child transmission rate of 18-month-old children were 1.36%(5/368),4.35%(16/368),and 2.01%(5/249),respectively.The incidence of stunted growth of 18-month-old children in the case group and the control group was 42.12%(155/368)and 23.06%(101/438),respectively,with significant difference(
Case-Control Studies ; China/epidemiology* ; Female ; Growth and Development ; HIV ; HIV Infections/prevention & control* ; Humans ; Infant ; Infectious Disease Transmission, Vertical/prevention & control* ; Mothers ; Pregnancy ; Pregnancy Complications, Infectious/drug therapy* ; Retrospective Studies

OBJECTIVE To explore the pathogenesis of depression according to the LC-MS/MS-based metabolo?mics in the mouse model which exhibits social avoidance state induced by the chronic social defeat stress model (CSDS). METHODS Twenty male C57BL/6N mice were randomly divided into control group and model group suffering CSDS, and the ICR retired breeder mice were used to attack the model group for 14 d of chronic social defeated stress. The open field test and source preference test were both used to observe depression-like behavior. Besides, the social inter?action test is used to observe the social interaction state, especially. After the stress, the serum samples of mice were collected, and the changes of endogenous metabolites were analyzed by LC-MS metabolomics technology, and the pathway analysis of the differential metabolites was performed to explore the pathogenesis of the CSDS induced depres?sive-like mouse model. RESULTS After the stress of CSDS was completed, the mice in the model group showed a significant slowdown in body weight growth, a reduction in the source preference rate, and a significant reduction in the total distance and the number of rearing in the open field test. Distinctively, the social interaction rate is remarkably decreasing. There are 24 differential metabolites found in the serum of CSDS model mice. CONCLUSION The mouse who suffered CSDS stress would show depressive-like behavior. Based on the LC-MS/MS metabolomics, 24 differential metabolites were found in the serum of CSDS model mice. The amino acid metabolism might be significant to the patho?genesis of the CSDS induced depressive-like mouse model.

Objective::To predict the action targets of anti-lung cancer active ingredients of Xiao Chaihutang, in order to explore the " multi-components, multi-targets and multi-pathways" mechanism using network pharmacology. Method::The active ingredients of Xiao Chaihutang that obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), traditional Chinese medicine integrative database for herb molecular mechanism analysis(TCMID) and literature were used to predict the targets by the reversed pharmacophore matching method.To screen out optimization targets, we chose elbow point analysis by using self-developed software TCMKD1.0, and screened out lung cancer-related targets by searching databases, such as Therapeutic Target Database (TTD), Online Mendelian Inheritance in Man(OMIM) and GeneCards, and reviewing literatures.Then components-target network, protein-protein interaction network and targets-pathways network were constructed.The pathway information was acquired with STRING.The Cytoscape 3.6 software was used to construct the ingredients-targets-pathways network of Xiao Chaihutang. Result::The 162 active components in Xiao Chaihutang were obtained, involving 71 anti-lung cancer targets and 11 related pathways.Through topological network analysis, 96 important components, such as quercetin, ginsenosideRh₂, formononetin and β-sitosterol were obtained, 28 key targets, such as epidermal growth factor receptor (EGFR), vascular endothelial growth factor (KDR), cysteine protease-3 (Caspase-3), mitogen-activated protein kinase1(MAPK1), hepatocyte growth factor (MET) were received, and 61 core pathways, such as non-small cell lung cancer, small cell lung cancer, ErbB signaling pathway, VEGF signaling pathway were acquired. Conclusion::The result suggests that the active components of Xiao Chaihutang against lung cancer may include quercetin, ginsenoside Rh₂, 6-shogaol, formononetin, β-sitosterol.And the mechanism may be related to ErbB signaling pathway, MAPK signaling pathway and VEGF signaling pathway.This research provides a scientific basis for further elucidation of the anti-lung cancer pharmacological mechanism of Xiao Chaihutang.