1.Mechanism of Yishen Huoxue Tongqiao Formula in Improving Unilateral Vestibular Labyrinth Destruction by Regulating Metabolism-neuroplasticity
Yu TIAN ; Hui LENG ; Rupeng QU ; Xianglong HAO ; Aiping WANG ; Lei SHI ; Zhongyuan QU ; Ye DONG ; Xiande MA ; Yangling HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):54-64
ObjectiveThis study aims to explore the mechanism by which Yishen Huoxue Tongqiao Formula improves metabolism-neuroplasticity and treats unilateral vestibular labyrinth destruction by regulating the metabolic balance of glutamate (Glu)/γ-aminobutyric acid (GABA). Methods48 Sprague-Dawley (SD) adult rats were randomly divided into the sham operation group, model group, Yishen Huoxue Tongqiao Formula groups with low, medium, and high doses (9.20, 18.39, 36.78 g·kg-1), and betahistine group (1.62 mg·kg-1). A unilateral vestibular labyrinth destruction (vestibular dysfunction) model was established by intratympanic injection of chloroform into the right ear, while the control group received intratympanic injection of normal saline. Drugs were administered once daily for seven consecutive days. During the period, behavioral tests were performed to evaluate the behaviors of rats after unilateral vestibular labyrinth destruction. Hematoxylin-eosin (HE) staining and Nissl staining were used to observe the neuronal morphology in the medial vestibular nucleus. Golgi staining was employed to assess the number of dendritic spines of neurons in the medial vestibular nucleus. Ultra-performance liquid chromatography-tandem mass spectrometry (LC-ESI-MS/MS) was utilized to detect Glu/GABA. Immunofluorescence and immunohistochemistry were used to detect the expressions of neuronal nuclei (NeuN), growth-associated protein 43 (GAP-43), and glial fibrillary acidic protein (GFAP). Western blot and real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) were applied to determine the expressions of glutamate-immunoreactive (Glu-IR), GABA, GFAP, postsynaptic density protein 95 (PSD-95), and GAP-43. ResultsCompared with the sham operation group, the model group presented with head deviation, balance disorder, increased tail suspension score, nuclear consolidation of medial vestibular nerve neurons, and decreased Nissl bodies (P<0.01). The number of dendritic spines in neurons and NeuN-positive cells decreased. The content of Glu decreased. The content of GABA increased (Glu/GABA decreased). The expression of GAP-43 was down-regulated, and GFAP was up-regulated (P<0.05, P<0.01). The expressions of Glu-IR, PSD-95, and GAP-43 proteins, as well as Glu-IR mRNA decreased, while the expressions of GABA and GFAP proteins and mRNA increased (P<0.05, P<0.01). Compared with those in the model group, the head deviation, imbalanced behavior, and tail suspension scores in each treatment group decreased, with alleviated neuronal injury and recovered Nissl bodies (P<0.01). The number of dendritic spines of neurons increased, and the number of NeuN-positive cells rebounded. The content of Glu increased, and the content of GABA decreased (Glu/GABA increased). GFAP was down-regulated, and GAP-43 was up-regulated (P<0.05, P<0.01). The expressions of Glu-IR, PMD-95, and GAP-43 proteins, as well as Glu-IR mRNA increased, while the expressions of GABA and GFAP proteins and mRNA decreased. The effect was more significant in the high-dose group (P<0.01). ConclusionThe Yishen Huoxue Tongqiao Formula can alleviate vestibular dysfunction, and its mechanism may be associated with regulating the metabolic balance of Glu/GABA, mitigating neural damage, improving synaptic plasticity (promoting GAP-43 expression and inhibiting GFAP expression), and facilitating vestibular compensation.
2.Analysis of related factors for the comorbidity of allergic rhinitis and obesity among primary and secondary school students in Inner Mongolia
Chinese Journal of School Health 2026;47(1):27-31
Objective:
To investigate the factors influencing the co-prevalence of allergic rhinitis and obesity among primary and secondary school students in Inner Mongolia, so as to provide a data foundation and theoretical basis for developing targeted intervention measures.
Methods:
In September and October 2024, a stratified cluster random sampling method was employed to select 139 102 students from 539 schools across 12 leagues/cities and 103 banners/counties in Inner Mongolia Autonomous Region. Participants who were diagnosed with allergic rhinitis by a doctor at least once within one year and had a body mass index ≥ 28 kg/m 2 were considered to have comorbid conditions.
Results:
The coprevalence rate of allergic rhinitis and obesity among primary and secondary school students in Inner Mongolia was 6.4% (8 931 cases). Lasso-Logistic regression revealed that nonboarding status, higher maternal education, consuming high protein foods ≥1 time daily, occasionally or never eating breakfast, engaging in moderate to vigorous physical activity for ≥60 minutes on fewer than half of holidays, and having been exposed to second hand smoke in person within the past seven days were associated with higher odds ratios for co-prevalence of allergic rhinitis and obesity( OR = 1.23 , 1.22-1.63, 1.20, 1.19, 1.38, 1.35); being female, higher grade level, residence in flag/county/district areas, non only child status, never having consumed a full glass of alcohol, non hypertensive status, and households without pets were associated with lower co-prevalence risks ( OR =0.65, 0.67-0.77, 0.81, 0.87, 0.73, 0.41, 0.68) (all P <0.05). The ROC curve indicated an area under the curve of 0.64 for the predictive model, demonstrating satisfactory discriminatory ability. The calibration curve showed consistency between predicted and actual occurrence probabilities.
Conclusions
The co-prevalence of allergic rhinitis and obesity among primary and secondary school students in Inner Mongolia is closely associated with demographic characteristics, dietary behaviours, and lifestyle habits. Future prevention and control strategies should prioritize these factors to implement targeted interventions.
3.Evaluation of CARIFS Score and Negative Antigen Conversion Rate of Qingxuan Daozhi Formula in Treatment of Influenza in Children (Heat Accumulation in Lung and Stomach Syndrome):A Multi-center Randomized Controlled Clinical Study
Jing WANG ; Liqun WU ; Tiegang LIU ; Yongning CAO ; Jing QIU ; Jing LI ; Huaqing TAN ; Ying ZHANG ; Xulei GOU ; Jia WANG ; Jing LI ; Haipeng CHEN ; Xueying QIN ; Yuanshuo TIAN ; Yang WANG ; Chen BAI ; Zhendong WANG ; Qianqian LI ; He YU ; Xueyan MA ; Fei DONG ; Lin JIANG ; Yingqi XU ; Jianping LIU ; Xiaohong GU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(13):188-196
ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children (heat accumulation in the lung and stomach syndrome). MethodsThrough a multi-center randomized controlled methodology design,confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals,such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days,and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale (CARIFS) and the incidence of complications,severe cases, and critical cases. Follow-up observation was conducted on the day of enrollment,48 hours after medication,72 hours after medication, and (6+1) d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group (90 cases) or the control group (90 cases). All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was (5.29±1.25) d,and that in the control group was (5.40±1.68) d,without a statistically significant difference. After five days of intervention,52 cases in the experimental group and 51 cases in the control group converted to negative,without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention,there were statistically significant differences between the experimental group and the control group in three dimensions, including headache,muscle soreness, and the need for extra care (P<0.05). On the (6+1) days after the intervention,the differences in both the experimental group and the control group were statistically significant in 10 dimensions, including sore throat,bad sleep,uncomfortable feeling,poor spirit and fatigue,crying more than usual,the need for extra care,symptom,function,influence on parents,and total score (P<0.05). The comparison results within the group in the dimensional scores of symptom, function, and influence on parents,as well as the CARIFS total score showed that with the delay of follow-up time,scores of both groups decreased significantly,with a statistically significant difference (P<0.01). Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention,the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up,the mean score of the experimental group was lower than that of the control group,with no statistically significant difference. In terms of the incidence of complications,severe cases, and critical cases, there were no complications,severe cases, and critical cases in the two groups,without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children (heat accumulation in the lung and stomach syndrome) are not inferior to Oseltamivir Phosphate granules, and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children (heat accumulation in the lung and stomach syndrome).
4.Adolescent Smoking Addiction Diagnosis Based on TI-GNN
Xu-Wen WANG ; Da-Hua YU ; Ting XUE ; Xiao-Jiao LI ; Zhen-Zhen MAI ; Fang DONG ; Yu-Xin MA ; Juan WANG ; Kai YUAN
Progress in Biochemistry and Biophysics 2025;52(9):2393-2405
ObjectiveTobacco-related diseases remain one of the leading preventable public health challenges worldwide and are among the primary causes of premature death. In recent years, accumulating evidence has supported the classification of nicotine addiction as a chronic brain disease, profoundly affecting both brain structure and function. Despite the urgency, effective diagnostic methods for smoking addiction remain lacking, posing significant challenges for early intervention and treatment. To address this issue and gain deeper insights into the neural mechanisms underlying nicotine dependence, this study proposes a novel graph neural network framework, termed TI-GNN. This model leverages functional magnetic resonance imaging (fMRI) data to identify complex and subtle abnormalities in brain connectivity patterns associated with smoking addiction. MethodsThe study utilizes fMRI data to construct functional connectivity matrices that represent interaction patterns among brain regions. These matrices are interpreted as graphs, where brain regions are nodes and the strength of functional connectivity between them serves as edges. The proposed TI-GNN model integrates a Transformer module to effectively capture global interactions across the entire brain network, enabling a comprehensive understanding of high-level connectivity patterns. Additionally, a spatial attention mechanism is employed to selectively focus on informative inter-regional connections while filtering out irrelevant or noisy features. This design enhances the model’s ability to learn meaningful neural representations crucial for classification tasks. A key innovation of TI-GNN lies in its built-in causal interpretation module, which aims to infer directional and potentially causal relationships among brain regions. This not only improves predictive performance but also enhances model interpretability—an essential attribute for clinical applications. The identification of causal links provides valuable insights into the neuropathological basis of addiction and contributes to the development of biologically plausible and trustworthy diagnostic tools. ResultsExperimental results demonstrate that the TI-GNN model achieves superior classification performance on the smoking addiction dataset, outperforming several state-of-the-art baseline models. Specifically, TI-GNN attains an accuracy of 0.91, an F1-score of 0.91, and a Matthews correlation coefficient (MCC) of 0.83, indicating strong robustness and reliability. Beyond performance metrics, TI-GNN identifies critical abnormal connectivity patterns in several brain regions implicated in addiction. Notably, it highlights dysregulations in the amygdala and the anterior cingulate cortex, consistent with prior clinical and neuroimaging findings. These regions are well known for their roles in emotional regulation, reward processing, and impulse control—functions that are frequently disrupted in nicotine dependence. ConclusionThe TI-GNN framework offers a powerful and interpretable tool for the objective diagnosis of smoking addiction. By integrating advanced graph learning techniques with causal inference capabilities, the model not only achieves high diagnostic accuracy but also elucidates the neurobiological underpinnings of addiction. The identification of specific abnormal brain networks and their causal interactions deepens our understanding of addiction pathophysiology and lays the groundwork for developing targeted intervention strategies and personalized treatment approaches in the future.
5.Prevalence trends of elevated blood pressure and its association with nutritional status among primary and secondary school students in Inner Mongolia
Chinese Journal of School Health 2025;46(9):1342-1345
Objective:
To analyze the prevalence trends of different types of elevated blood pressure and their association with nutritional status among primary and secondary school students in Inner Mongolia from 2019 to 2024, providing references for targeted prevention strategies.
Methods:
From September 2019 to 2024, a stratified random cluster sampling method was used to select 12 primary and secondary schools from each league city in Inner Mongolia Autonomous Region. A total of 177 108, 137 758, 190 182, 180 084 , 188 056, 180 351 primary and secondary school students (excluding grades one to three of primary school) were included for physical examination. The correlation between their nutritional status and high blood pressure was analyzed based on the basic situation of 129 821 primary and secondary school students who completed a questionnaire survey at the same time in 2024. Statistical analysis was conducted using a Chi-square test and multiple Logistic regression model.
Results:
From 2019 to 2024, the detection rates of elevated blood pressure were 13.60%, 13.68%, 17.60%, 17.24%, 14.77% and 15.96%, respectively. The rates for isolated systolic hypertension were 4.24%, 5.83%, 7.26%, 7.19%, 6.24% and 6.93%; isolated diastolic hypertension rates were 6.38%, 4.99%, 6.23 %, 6.41%, 5.39% and 5.66%; and combined systolic and diastolic hypertension rates were 2.97%, 2.86%, 4.11%, 3.65%, 3.14 % and 3.36%. Multivariate Logistic regression analysis showed that girls, junior high school, senior high school, overweight, and obesity were positively associated with elevated blood pressure risk ( OR =1.27, 1.25, 1.32, 1.66, 3.07, all P <0.05); conversely, county residence, Mongolian ethnicity, and other ethnicities showed negative associations ( OR =0.90, 0.93, 0.90, all P <0.05).
Conclusions
Overweight and obesity among children and adolescents are closely related to various types of elevated blood pressure. Prevention strategies should prioritize effectively controlling weight issues among children and adolescents, thereby effectively reducing the incidence of elevated blood pressure.
6.Clinical Efficacy of Xiaoji Hufei Formula in Protecting Children with Close Contact Exposure to Influenza: A Multicenter,Prospective, Non-randomized, Parallel, Controlled Trial
Jing WANG ; Jianping LIU ; Tiegang LIU ; Hong WANG ; Yingxin FU ; Jing LI ; Huaqing TAN ; Yingqi XU ; Yanan MA ; Wei WANG ; Jia WANG ; Haipeng CHEN ; Yuanshuo TIAN ; Yang WANG ; Chen BAI ; Zhendong WANG ; Qianqian LI ; He YU ; Xueyan MA ; Fei DONG ; Liqun WU ; Xiaohong GU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):223-230
ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza, and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter, prospective, non-randomized, parallel, controlled trial was conducted from October 2021 to May 2022 in five hospitals, including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness (ILI) cases were collected, and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention, they were assigned to the observation group (108 cases) or the control group (108 cases). Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine (TCM) symptom score scale for influenza, influenza-related emergency (outpatient) visit rate, influenza hospitalization rate, and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled, with 108 in the observation group and 108 in the control group. Primary outcomes: (1) Incidence of ILI: The incidence was 12.0% (13/108) in the observation group and 23.1% (25/108) in the control group, with the observation group showing a significantly lower incidence (χ2=4.6, P<0.05). (2) Influenza confirmation rate: 3.7% (4/108) in the observation group and 4.6% (5/108) in the control group, with no statistically significant difference. Secondary outcomes: (1) TCM symptom score scale: after onset, nasal congestion and runny nose scores differed significantly between the two groups (P<0.05), while other symptoms such as fever, sore throat, and cough showed no significant differences. (2) Influenza-related emergency (outpatient) visit rate: 84.6% (11 cases) in the observation group and 96.0% (24 cases) in the control group, with no significant difference. (3) Time to onset after exposure: The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group, with a statistically significant difference (P<0.05). ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions, Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.
7.Clinical Efficacy of Xiaoji Hufei Formula in Protecting Children with Close Contact Exposure to Influenza: A Multicenter,Prospective, Non-randomized, Parallel, Controlled Trial
Jing WANG ; Jianping LIU ; Tiegang LIU ; Hong WANG ; Yingxin FU ; Jing LI ; Huaqing TAN ; Yingqi XU ; Yanan MA ; Wei WANG ; Jia WANG ; Haipeng CHEN ; Yuanshuo TIAN ; Yang WANG ; Chen BAI ; Zhendong WANG ; Qianqian LI ; He YU ; Xueyan MA ; Fei DONG ; Liqun WU ; Xiaohong GU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):223-230
ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza, and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter, prospective, non-randomized, parallel, controlled trial was conducted from October 2021 to May 2022 in five hospitals, including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness (ILI) cases were collected, and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention, they were assigned to the observation group (108 cases) or the control group (108 cases). Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine (TCM) symptom score scale for influenza, influenza-related emergency (outpatient) visit rate, influenza hospitalization rate, and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled, with 108 in the observation group and 108 in the control group. Primary outcomes: (1) Incidence of ILI: The incidence was 12.0% (13/108) in the observation group and 23.1% (25/108) in the control group, with the observation group showing a significantly lower incidence (χ2=4.6, P<0.05). (2) Influenza confirmation rate: 3.7% (4/108) in the observation group and 4.6% (5/108) in the control group, with no statistically significant difference. Secondary outcomes: (1) TCM symptom score scale: after onset, nasal congestion and runny nose scores differed significantly between the two groups (P<0.05), while other symptoms such as fever, sore throat, and cough showed no significant differences. (2) Influenza-related emergency (outpatient) visit rate: 84.6% (11 cases) in the observation group and 96.0% (24 cases) in the control group, with no significant difference. (3) Time to onset after exposure: The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group, with a statistically significant difference (P<0.05). ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions, Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.
8.Optimization of water extraction technology of Kaixin granules
Zuomin WU ; Shuxian BAI ; Meng NING ; Yunzhi WANG ; Huifen MA ; Jingyuan DONG ; Zhongjie YANG ; Zhishen XIE ; Zhenqiang ZHANG ; Xiaotao YU
China Pharmacy 2025;36(22):2790-2795
OBJECTIVE To optimize the water extraction technology for Kaixin granules. METHODS UPLC-MS/MS method was established for the simultaneous determination of ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1, tenuifolin, polygalaxanthone Ⅲ and 3, 6′-disinapoyl-sucrose. An orthogonal test was designed with extraction times, extraction duration, and the volume of added water as factors. Using the contents of the aforementioned six indicator components and the extract yield as evaluation indexes, analytic hierarchy process-entropy weight method was employed to determine the combined weights of each indicator. Subsequently, process optimization and validation were conducted by integrating grey relational analysis (GRA) and back propagation (BP) neural network. RESULTS The water extraction technology optimized by the orthogonal test and GRA was 10- fold water for the first decoction and 8-fold water for the subsequent two, extracting 3 times,extracting for 1 h each time; the average comprehensive score of the validation experiment was 91.10 (RSD=0.31%, n=3). The water extraction technology optimized by BP neural network was extracting 3 times with 10-fold water added each time, extracting for 1.5 h each time; the average comprehensive score of the validation experiment was 95.89 (RSD=0.73%, n=3). Considering practical production requirements, the optimal water extraction technology was extraction performed three times, with 10-fold water for the first decoction and 8-fold water for the subsequent two extractions, with an extraction time of 1 h each. CONCLUSIONS The optimized water extraction technology for Kaixin granules is stable and feasible.
9.Omics in IgG4-related disease.
Shaozhe CAI ; Yu CHEN ; Ziwei HU ; Shengyan LIN ; Rongfen GAO ; Bingxia MING ; Jixin ZHONG ; Wei SUN ; Qian CHEN ; John H STONE ; Lingli DONG
Chinese Medical Journal 2025;138(14):1665-1675
Research on IgG4-related disease (IgG4-RD), an autoimmune condition recognized to be a unique disease entity only two decades ago, has processed from describing patients' symptoms and signs to summarizing its critical pathological features, and further to investigating key pathogenic mechanisms. Challenges in gaining a better understanding of the disease, however, stem from its relative rarity-potentially attributed to underrecognition-and the absence of ideal experimental animal models. Recently, with the development of various high-throughput techniques, "omics" studies at different levels (particularly the single-cell omics) have shown promise in providing detailed molecular features of IgG4-RD. While, the application of omics approaches in IgG4-RD is still at an early stage. In this paper, we review the current progress of omics research in IgG4-RD and discuss the value of machine learning methods in analyzing the data with high dimensionality.
Humans
;
Immunoglobulin G4-Related Disease/metabolism*
;
Immunoglobulin G/metabolism*
;
Machine Learning
;
Animals
;
Proteomics/methods*
10.Arsenic trioxide preconditioning attenuates hepatic ischemia- reperfusion injury in mice: Role of ERK/AKT and autophagy.
Chaoqun WANG ; Hongjun YU ; Shounan LU ; Shanjia KE ; Yanan XU ; Zhigang FENG ; Baolin QIAN ; Miaoyu BAI ; Bing YIN ; Xinglong LI ; Yongliang HUA ; Zhongyu LI ; Dong CHEN ; Bangliang CHEN ; Yongzhi ZHOU ; Shangha PAN ; Yao FU ; Hongchi JIANG ; Dawei WANG ; Yong MA
Chinese Medical Journal 2025;138(22):2993-3003
BACKGROUND:
Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI.
METHODS:
In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy.
RESULTS:
A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent.
CONCLUSION
Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals
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Arsenic Trioxide
;
Autophagy/physiology*
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Reperfusion Injury/prevention & control*
;
Mice
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Male
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Proto-Oncogene Proteins c-akt/physiology*
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Arsenicals/therapeutic use*
;
Oxides/therapeutic use*
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Liver/metabolism*
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Extracellular Signal-Regulated MAP Kinases/metabolism*
;
Mice, Inbred C57BL


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