1.Effects of Huanglian Jiedutang on Neutrophil Infiltration in Brain of MCAO Mice via Regulation of Chemokine Expression in Exosomes
Haojia ZHANG ; Kai WANG ; Zijin SUN ; Chunyu WANG ; Wei SHAO ; Kunjing LIU ; Liyang DONG ; Dan CHEN ; Wenxiu XU ; Chuanzun WANG ; Wen WANG ; Changxiang LI ; Xueqian WANG ; Fafeng CHENG ; Qingguo WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):42-53
ObjectiveTo investigate whether Huanglian Jiedutang can inhibit neutrophil infiltration in the brains of middle cerebral artery occlusion (MCAO) mice by regulating the expression of neutrophil-related chemokines in exosomes, thereby achieving therapeutic effects. MethodsA total of 130 male specific pathogen-free (SPF) C57BL/6J mice were randomly divided into four groups: Sham-operated group, MCAO model group, Huanglian Jiedutang group (6 g·kg-1), and Ginaton group (21.6 mg·kg-1), with 10 mice in the Ginaton group and 40 mice in each of the remaining three groups. Mice in the Huanglian Jiedutang group and the Ginaton group were administered the corresponding drugs by oral gavage once daily at a volume of 0.15 mL·(10 g)-1 for 7 consecutive days, while the sham-operated and model groups received an equal volume of saline via the same route. After 7 days, MCAO surgery was performed. The distal and proximal ends of the right common carotid artery (CCA) were ligated, a small incision was made between the two ligatures, and a silicone rubber-coated monofilament with a rounded tip was inserted into the lumen to occlude the CCA. The filament was left in place for 1 h to establish a focal cerebral ischemia model. At 24 h after modeling, mice were evaluated. Neurological function was assessed using the Longa score. Cerebral infarct volume was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Cerebral blood flow was observed by laser speckle imaging. Hematoxylin and eosin (HE) staining and Nissl staining were used to observe pathological changes in brain tissues. Exosomes were isolated from mouse plasma and brain tissues by ultracentrifugation and molecular size exclusion and identified by electron microscopy, particle size analysis, and protein blotting. Long-chain RNA libraries of exosomes were constructed and sequenced. Real-time quantitative reverse transcription polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of inflammatory factors and neutrophil-related chemokines in exosomes from plasma and brain tissues of each group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the protein expression of inflammatory factors and neutrophil-related chemokines in exosomes from brain tissues of each group. Immunohistochemistry was used to detect the expression of the neutrophil-specific protein myeloperoxidase (MPO) in the brains of mice in each group. ResultsCompared with the sham-operated group, the model group showed decreased neurological function scores (P<0.01), obvious cerebral infarction (P<0.01), reduced cerebral blood flow (P<0.01), neuronal necrosis in the brain, and decreased numbers of Nissl bodies (P<0.01). The mRNA expression levels of IL-1β, MPO, CXCL1, CXCL2, CXCL3, CXCL10, CCL2, and CCL3 in exosomes from plasma and brain tissues were significantly increased (P<0.05, P<0.01). The protein expression levels of IL-1β, MPO, CXCL2, and CXCL10 in exosomes from brain tissues were increased (P<0.05, P<0.01), and MPO-positive rates and mean optical density values in brain tissues were elevated (P<0.01). Compared with the model group, the Huanglian Jiedutang group and the Ginaton group showed increased neurological function scores (P<0.05), reduced cerebral infarct volume (P<0.01), restored cerebral blood flow (P<0.01), reduced necrotic cells in the brain, and increased numbers of Nissl bodies (P<0.01). In the Huanglian Jiedutang group, the mRNA expression levels of IL-1β, MPO, CXCL1, CXCL2, CXCL3, CXCL10, CCL2, and CCL3 in exosomes from plasma and brain tissues were decreased (P<0.05, P<0.01). The protein expression levels of IL-1β, MPO, CXCL2, and CXCL10 in exosomes from brain tissues were reduced (P<0.05, P<0.01), and MPO-positive rates and mean optical density values in brain tissues were decreased (P<0.01). ConclusionHuanglian Jiedutang can effectively regulate the expression of neutrophil-related chemokines in exosomes from plasma and brain tissues of MCAO mice, thereby reducing neutrophil infiltration in the brain and achieving therapeutic effects.
2.Effects of Huanglian Jiedutang on Neutrophil Infiltration in Brain of MCAO Mice via Regulation of Chemokine Expression in Exosomes
Haojia ZHANG ; Kai WANG ; Zijin SUN ; Chunyu WANG ; Wei SHAO ; Kunjing LIU ; Liyang DONG ; Dan CHEN ; Wenxiu XU ; Chuanzun WANG ; Wen WANG ; Changxiang LI ; Xueqian WANG ; Fafeng CHENG ; Qingguo WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):42-53
ObjectiveTo investigate whether Huanglian Jiedutang can inhibit neutrophil infiltration in the brains of middle cerebral artery occlusion (MCAO) mice by regulating the expression of neutrophil-related chemokines in exosomes, thereby achieving therapeutic effects. MethodsA total of 130 male specific pathogen-free (SPF) C57BL/6J mice were randomly divided into four groups: Sham-operated group, MCAO model group, Huanglian Jiedutang group (6 g·kg-1), and Ginaton group (21.6 mg·kg-1), with 10 mice in the Ginaton group and 40 mice in each of the remaining three groups. Mice in the Huanglian Jiedutang group and the Ginaton group were administered the corresponding drugs by oral gavage once daily at a volume of 0.15 mL·(10 g)-1 for 7 consecutive days, while the sham-operated and model groups received an equal volume of saline via the same route. After 7 days, MCAO surgery was performed. The distal and proximal ends of the right common carotid artery (CCA) were ligated, a small incision was made between the two ligatures, and a silicone rubber-coated monofilament with a rounded tip was inserted into the lumen to occlude the CCA. The filament was left in place for 1 h to establish a focal cerebral ischemia model. At 24 h after modeling, mice were evaluated. Neurological function was assessed using the Longa score. Cerebral infarct volume was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Cerebral blood flow was observed by laser speckle imaging. Hematoxylin and eosin (HE) staining and Nissl staining were used to observe pathological changes in brain tissues. Exosomes were isolated from mouse plasma and brain tissues by ultracentrifugation and molecular size exclusion and identified by electron microscopy, particle size analysis, and protein blotting. Long-chain RNA libraries of exosomes were constructed and sequenced. Real-time quantitative reverse transcription polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of inflammatory factors and neutrophil-related chemokines in exosomes from plasma and brain tissues of each group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the protein expression of inflammatory factors and neutrophil-related chemokines in exosomes from brain tissues of each group. Immunohistochemistry was used to detect the expression of the neutrophil-specific protein myeloperoxidase (MPO) in the brains of mice in each group. ResultsCompared with the sham-operated group, the model group showed decreased neurological function scores (P<0.01), obvious cerebral infarction (P<0.01), reduced cerebral blood flow (P<0.01), neuronal necrosis in the brain, and decreased numbers of Nissl bodies (P<0.01). The mRNA expression levels of IL-1β, MPO, CXCL1, CXCL2, CXCL3, CXCL10, CCL2, and CCL3 in exosomes from plasma and brain tissues were significantly increased (P<0.05, P<0.01). The protein expression levels of IL-1β, MPO, CXCL2, and CXCL10 in exosomes from brain tissues were increased (P<0.05, P<0.01), and MPO-positive rates and mean optical density values in brain tissues were elevated (P<0.01). Compared with the model group, the Huanglian Jiedutang group and the Ginaton group showed increased neurological function scores (P<0.05), reduced cerebral infarct volume (P<0.01), restored cerebral blood flow (P<0.01), reduced necrotic cells in the brain, and increased numbers of Nissl bodies (P<0.01). In the Huanglian Jiedutang group, the mRNA expression levels of IL-1β, MPO, CXCL1, CXCL2, CXCL3, CXCL10, CCL2, and CCL3 in exosomes from plasma and brain tissues were decreased (P<0.05, P<0.01). The protein expression levels of IL-1β, MPO, CXCL2, and CXCL10 in exosomes from brain tissues were reduced (P<0.05, P<0.01), and MPO-positive rates and mean optical density values in brain tissues were decreased (P<0.01). ConclusionHuanglian Jiedutang can effectively regulate the expression of neutrophil-related chemokines in exosomes from plasma and brain tissues of MCAO mice, thereby reducing neutrophil infiltration in the brain and achieving therapeutic effects.
3.Evaluation of the application effectiveness and optimization strategies of confidential unit exclusion in Zhengzhou
Dan LIU ; Hongwei MA ; Tao WEN ; Yonglei LYU ; Mengru JI ; Ge SONG ; Huanyu LIU ; Mengdi FAN
Chinese Journal of Blood Transfusion 2026;39(3):379-383
Objective: To evaluate the practical effectiveness of confidential unit exclusion (CUE) in ensuring blood safety in Zhengzhou, analyze its application characteristics and existing problems, and provide a basis for optimizing blood safety management strategies. Methods: A retrospective analysis was conducted on CUE data handled by Henan Red Cross Blood Center from January 2019 to December 2024. Parameters such as the number of cases, demographic characteristics, reasons for exclusion, and time of report were statistically analyzed and compared with those of non-CUE. Results: From 2019 to 2024, the CUE reporting rate in Zhengzhou was 0.002 6% (40/1 547 666). CUE donors were predominantly male (65.00%, 26/40), aged 18-34 years (47.50%, 19/40), had college degree orabove (50.00%, 20/40), and were employees of enterprises or public institutions (32.50%, 13/40). Among the 40 CUE blood units, only one was reactive for anti-TP, while all others were qualified. The main reasons for CUE were recent vaccination (32.50%, 13/40), medical conditions unsuitable for donation (27.50%, 11/40), and high-risk sexual behavior (17.50%, 7/40). A total of 70.00% of reports occurred within 24 hours after donation, during which none of the corresponding blood units had been released; all units reported after more than 7 days had already been issued for clinical use, with no adverse transfusion reactions reported upon follow-up. Conclusion: The confidential unit exclusion program has played an active role in establishing a supplementary information feedback channel for blood donors. The procedure can be optimized by strengthening interactive communication and confirmation before donation, improving the accuracy of donors' self-assessment, and expanding convenient and rapid information-based reporting channels.
4.Targeting PPARα for The Treatment of Cardiovascular Diseases
Tong-Tong ZHANG ; Hao-Zhuo ZHANG ; Li HE ; Jia-Wei LIU ; Jia-Zhen WU ; Wen-Hua SU ; Ju-Hua DAN
Progress in Biochemistry and Biophysics 2025;52(9):2295-2313
Cardiovascular disease (CVD) remains one of the leading causes of mortality among adults globally, with continuously rising morbidity and mortality rates. Metabolic disorders are closely linked to various cardiovascular diseases and play a critical role in their pathogenesis and progression, involving multifaceted mechanisms such as altered substrate utilization, mitochondrial structural and functional dysfunction, and impaired ATP synthesis and transport. In recent years, the potential role of peroxisome proliferator-activated receptors (PPARs) in cardiovascular diseases has garnered significant attention, particularly peroxisome proliferator-activated receptor alpha (PPARα), which is recognized as a highly promising therapeutic target for CVD. PPARα regulates cardiovascular physiological and pathological processes through fatty acid metabolism. As a ligand-activated receptor within the nuclear hormone receptor family, PPARα is highly expressed in multiple organs, including skeletal muscle, liver, intestine, kidney, and heart, where it governs the metabolism of diverse substrates. Functioning as a key transcription factor in maintaining metabolic homeostasis and catalyzing or regulating biochemical reactions, PPARα exerts its cardioprotective effects through multiple pathways: modulating lipid metabolism, participating in cardiac energy metabolism, enhancing insulin sensitivity, suppressing inflammatory responses, improving vascular endothelial function, and inhibiting smooth muscle cell proliferation and migration. These mechanisms collectively reduce the risk of cardiovascular disease development. Thus, PPARα plays a pivotal role in various pathological processes via mechanisms such as lipid metabolism regulation, anti-inflammatory actions, and anti-apoptotic effects. PPARα is activated by binding to natural or synthetic lipophilic ligands, including endogenous fatty acids and their derivatives (e.g., linoleic acid, oleic acid, and arachidonic acid) as well as synthetic peroxisome proliferators. Upon ligand binding, PPARα activates the nuclear receptor retinoid X receptor (RXR), forming a PPARα-RXR heterodimer. This heterodimer, in conjunction with coactivators, undergoes further activation and subsequently binds to peroxisome proliferator response elements (PPREs), thereby regulating the transcription of target genes critical for lipid and glucose homeostasis. Key genes include fatty acid translocase (FAT/CD36), diacylglycerol acyltransferase (DGAT), carnitine palmitoyltransferase I (CPT1), and glucose transporter (GLUT), which are primarily involved in fatty acid uptake, storage, oxidation, and glucose utilization processes. Advancing research on PPARα as a therapeutic target for cardiovascular diseases has underscored its growing clinical significance. Currently, PPARα activators/agonists, such as fibrates (e.g., fenofibrate and bezafibrate) and thiazolidinediones, have been extensively studied in clinical trials for CVD prevention. Traditional PPARα agonists, including fenofibrate and bezafibrate, are widely used in clinical practice to treat hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) levels. These fibrates enhance fatty acid metabolism in the liver and skeletal muscle by activating PPARα, and their cardioprotective effects have been validated in numerous clinical studies. Recent research highlights that fibrates improve insulin resistance, regulate lipid metabolism, correct energy metabolism imbalances, and inhibit the proliferation and migration of vascular smooth muscle and endothelial cells, thereby ameliorating pathological remodeling of the cardiovascular system and reducing blood pressure. Given the substantial attention to PPARα-targeted interventions in both basic research and clinical applications, activating PPARα may serve as a key therapeutic strategy for managing cardiovascular conditions such as myocardial hypertrophy, atherosclerosis, ischemic cardiomyopathy, myocardial infarction, diabetic cardiomyopathy, and heart failure. This review comprehensively examines the regulatory roles of PPARα in cardiovascular diseases and evaluates its clinical application value, aiming to provide a theoretical foundation for further development and utilization of PPARα-related therapies in CVD treatment.
5.Analysis of developmental trajectories of oral hygiene compliance and its influencing factors in children after dental caries surgery
Dan LI ; Yan LIU ; Na LI ; Wen ZHAO ; Cen HUANG
Journal of Clinical Medicine in Practice 2025;29(17):65-70,84
Objective To explore the developmental trajectories of oral hygiene compliance and its influencing factors in children after dental caries surgery.Methods A prospective cohort study design was adopted.A total of 268 children who underwent dental caries surgery were selected as the research subjects.General and clinical data of the children were collected.The oral hygiene compli-ance changes after surgery were evaluated using the Oral Hygiene Compliance Scale.The develop-mental trajectories of oral hygiene compliance after surgery were described using the group-based traj-ectory model.Multivariate Logistic regression analysis was used to explore the influencing factors of the compliance developmental trajectories.Results The oral hygiene compliance of children after dental caries surgery could be divided into three types of developmental trajectories:the high-compliance slow-decline group[49(18.28%)],the medium-compliance slow-decline group[56(20.90%)],and the low-compliance stable-change group[163(60.82%)].Multivariate Logistic regression analysis showed that the child's gender,mother's educational level,fathers smoking history,annual per capi-ta household income,Social Support Scale score,Oral Health Self-Efficacy Scale score,and Expec-ted Social Impact Scale score were all independent influencing factors for the oral hygiene compliance to present different types of developmental trajectories(P<0.05).Conclusion The oral hygiene compliance of children after dental caries surgery presents different types of developmental trajectories,and there are individual differences in their initial compliance levels and rates of change.Clinically,oral hygiene care intervention measures should be implemented according to the specific conditions of children to maintain their oral health.
6.Intraspecific variation of Forsythia suspensa chloroplast genome.
Yu-Han LI ; Lin-Lin CAO ; Chang GUO ; Yi-Heng WANG ; Dan LIU ; Jia-Hui SUN ; Sheng WANG ; Gang-Min ZHANG ; Wen-Pan DONG
China Journal of Chinese Materia Medica 2025;50(8):2108-2115
Forsythia suspensa is a traditional Chinese medicine and a commonly used landscaping plant. Its dried fruit is used in medicine for its functions of clearing heat, removing toxins, reducing swelling, dissipating masses, and dispersing wind and heat. It possesses extremely high medicinal and economic value. However, the genetic differentiation and diversity of its wild populations remain unclear. In this study, chloroplast genome sequences were obtained from 15 wild individuals of F. suspensa using high-throughput sequencing technology. The sequence characteristics and intraspecific variations were analyzed. The results were as follows:(1) The full length of the F. suspensa chloroplast genome ranged from 156 184 to 156 479 bp, comprising a large single-copy region, a small single-copy region, and two inverted repeat regions. The chloroplast genome encoded a total of 132 genes, including 87 protein-coding genes, 37 tRNA genes, and 8 rRNA genes.(2) A total of 166-174 SSR loci, 792 SNV loci, and 63 InDel loci were identified in the F. suspensa chloroplast genome, indicating considerable genetic variation among individuals.(3) Population structure analysis revealed that F. suspensa could be divided into five or six groups. Both the population structure analysis and phylogenetic reconstruction results indicated significant genetic variation within the wild populations of F. suspensa, with no obvious correlation between intraspecific genetic differentiation and geographical distribution. This study provides new insights into the genetic diversity and differentiation within F. suspensa species and offers additional references for the conservation of species diversity and the utilization of germplasm resources in wild F. suspensa.
Genome, Chloroplast
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Forsythia/classification*
;
Phylogeny
;
Genetic Variation
;
Chloroplasts/genetics*
;
Microsatellite Repeats
7.Associations of Genetic Risk and Physical Activity with Incident Chronic Obstructive Pulmonary Disease: A Large Prospective Cohort Study.
Jin YANG ; Xiao Lin WANG ; Wen Fang ZHONG ; Jian GAO ; Huan CHEN ; Pei Liang CHEN ; Qing Mei HUANG ; Yi Xin ZHANG ; Fang Fei YOU ; Chuan LI ; Wei Qi SONG ; Dong SHEN ; Jiao Jiao REN ; Dan LIU ; Zhi Hao LI ; Chen MAO
Biomedical and Environmental Sciences 2025;38(10):1194-1204
OBJECTIVE:
To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease.
METHODS:
This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used.
RESULTS:
During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity.
CONCLUSION
Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans
;
Pulmonary Disease, Chronic Obstructive/epidemiology*
;
Exercise
;
Male
;
Female
;
Middle Aged
;
Prospective Studies
;
Aged
;
Genetic Predisposition to Disease
;
Risk Factors
;
United Kingdom/epidemiology*
;
Incidence
;
Adult
8.Long-term outcomes of endoscopic papillectomy for duodenal papillary adenomas and risk factors for incomplete resection
Kun LIU ; Xintong ZHANG ; Xiang ZHANG ; Muhan NI ; Peng YAN ; Bei TANG ; Wenting LI ; Dan XU ; Wen LI ; Pin WANG ; Dehua TANG ; Xiaoping ZOU ; Lei WANG ; Shanshan SHEN
Chinese Journal of Digestive Endoscopy 2025;42(7):545-551
Objective:To evaluate long-term outcomes of endoscopic papillectomy (EP) for duodenal papillary adenomas and to identify risk factors for incomplete resection.Methods:Clinical data of 180 patients diagnosed as having duodenal papillary adenoma via postoperative pathology after EP in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from January 2010 to December 2022 were retrospectively analyzed. Patients were divided into two groups based on their postoperative margin status: the complete resection group (negative resection margins) and the incomplete resection group (positive/uncertain resection margins). Recurrence rates were compared between the two groups, and logistic regression analysis was performed to identify risk factors for incomplete resection.Results:Among the 180 patients included in the study, 137 underwent complete resection, and 43 had incomplete resections. Recurrence rate was significantly higher in the incomplete resection group than that in the complete resection group (30.2% VS 15.3%, χ2=4.75, P=0.029). logistic regression analysis indicated that high-grade intraepithelial neoplasia was an independent risk factor for incomplete resection ( OR=2.43, 95% CI:1.12-5.26, P=0.024). Conclusion:Patients with incomplete resection after EP have a higher recurrence rate in the long-term follow-up. High-grade intraepithelial neoplasia is an independent risk factor for incomplete resection. Close surveillance and aggressive management are warranted for patients with positive or uncertain resection margins to mitigate the recurrence risk.
9.Investigation on ventilator use and management in secondary and tertiary medical institutions in Sichuan Province
Zheng-hua LIANG ; Si-mei WANG ; Qiu-yu LIU ; Jin-long XU ; Ze-fang LIU ; Dan WEN
Chinese Medical Equipment Journal 2025;46(3):75-80
Objective To investigate the current situation of the ventilator use and management in secondary and tertiary medical institutions in Sichuan Province to provide references for management and training of ventilator users.Methods A questionnaire survey involving in 235 nurses from 13 secondary and tertiary medical institutions in Sichuan Province was conducted in terms of general information of the respondents,pipeline connection and parameter setup of ventilators,cleaning,sterilization and maintenance of ventilators,identification and treatment of ventilator alarms and hospital-acquired infection prevention and control.Results The results showed 20.4%of the respondents were nurses from critical care departments,and 79.6%of the respondents underwent the training for using the ventilator in their department;91.9%of the respondents could conduct ventilator self-testing by connecting the simulated lungs after the ventilator was switched on;66.4%of the respondents indicated that the initial parameters of the ventilator were set by the doctor;60.9%of the respondents proved that the performance monitoring and routine maintenance of the ventilator were carried out by the nurse;63.4%of the respondents showed disposable lines were commonly used in the departments.There were 89.8%of the respondents said the daily sterilization and management of the ventilator were performed by the nurse;46.0%of the respondents expressed the external surface of the ventilator was disinfected mainly with gamma disinfectant wipes;44.7%of the respondents indicated the external surface of the ventilator was sterilized every day;48.5%of the respondents said the internal airway of the ventilator was disinfected;57.0%of the respondents proved the disinfection was conducted after the expiratory flow sensors were used by any patient.There were 74.5%of the respondents that had paid attention to the ventilator waveform,and by the ventilator waveform only 21.3%were correct in determining whether there was secretion or fluid in the circuit and 22.1%in clarifying whether there was air leakage in the circuit.There were 59.1%of the respondents indicated that the closed suction tube was replaced once every 24 h;71.1%of the respondents could perform airbag pressure monitoring by the special pressure gauge.Conclusion Most of the nurses from secondary and tertiary medical institutions in Sichuan Province can use ventilators correctly,who have problems in disinfection specifications,infection prevention and control or recognition of ventilation waveform.It's suggested the training be strengthened to enhance the clinical nursing staffs in ventilator management.[Chinese Medical Equipment Journal,2025,46(3):75-80]
10.Compound Chaijin Jieyu formula modulates TLR4/NLRP3 signaling pathway to suppress central oxidative stress and ameliorate hippocampal synaptic plasticity impairment in depression
Lian-mei XUE ; De-guo LIU ; Qing-ping ZHANG ; Zi-rong LI ; Qian LIU ; Yi SHU ; Xiu-wen HUANG ; Li-dan LAN
Chinese Pharmacological Bulletin 2025;41(10):1972-1981
Aim To explore the mechanism by which the compound Chaijin Jieyu formula(CCJJY)regulates the TLR4/NLRP3 signaling pathway to inhibit central oxidative stress and improve hippocampal synaptic plasticity damage in depression.Methods SD rats were randomly divided into the control group,chronic unpredictable mild stress group,sleep deprivation group,chronic unpredictable mild stress combined with sleep deprivation group,positive drug group(venlafax-ine+melatonin),low-dose group of CCJJY,medium dose group of CCJJY,and high-dose group of CCJJY,with nine rats in each group.Except for the control group,a rat model of depression complicated with in-somnia was established using chronic unpredictable mild stress combined with sleep deprivation.Depres-sion-like and sleep behaviors in rats were evaluated through weight,food intake,water maze,and pento-barbital sodium tests.ELisa was used to detect ROS,AANAT,and HPLC-EC was used to detect 5-HT con-tent,while Western blot/RT-PCR was used to detect the expression of IL-1β,TLR4,NLRP3,PSD-95,and SYN related proteins and mRNA.HE and Golgic stai-ning were used to observe the pathological changes in the third ventricle,hippocampus,and neuronal synap-ses.Results Compared with the control group,the depression-like behaviors of the model group rats were significant.The expression of IL-1β,TLR4,and NL-RP3 in the hippocampus increased,while the expres-sion of PSD-95 and SYN decreased.Activation of NL-RP3 inflammasomes led to "sleeve like" pathological changes in the third ventricle,with hippocampal neu-rons undergoing apoptosis and significant damage to neuronal synaptic plasticity.Compared with the model group,after intervention with CCJJY,the expression of ROS,IL-1β,TLR4,and NLRP3 decreased,while the expression of AANAT,5-HT,PSD-95,and SYN in-creased.Pathological damage to the third ventricle and hippocampal neurons was repaired.Conclusion The CCJJY improves hippocampal synaptic plasticity dam-age in depression by regulating the TLR4/NLRP3 sig-naling pathway to inhibit central oxidative stress.

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