1.Mechanism of Wenyang Jieyu Prescription in Regulating Activation of Mouse Hippocampal Microglia Based on JAK2/STAT3 Signaling Pathway
Ying WANG ; Zihan GONG ; Wenqing LIANG ; Jingwen YANG ; Guangxin YUE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):88-96
ObjectiveTo explore the mechanism of the Wenyang Jieyu prescription in regulating depression-like behavior in mice after maternal-infant separation combined with secondary stress. MethodsAfter birth, the rats were randomly divided into blank (NC) group, maternal-infant separation (MS) group, restraint stress (RS) group, maternal-infant separation combined with restraint stress (MRS) group, Wenyang group, Jieyu group, Wenyang Jieyu (XSF) group, and minocycline group. Maternal-infant separation was performed on day 5 (PD5), followed by weaning at PD21 and prophylactic administration. The dose of Wenyang group, Xiaoyao group, XSF group and minocycline group were 5.85, 12.03, 16.71 g·kg-1 and 50 mg·kg-1, respectively. Restraint stress was applied on PD90. The model was evaluated using glucose, social interaction, open field, and O-maze behavior tests, as well as high-performance liquid chromatography to measure serotonin, dopamine, and other neurotransmitters. The expression level of ionized calcium-binding adaptor molecule-1 (Iba-1) protein, a marker of hippocampal microglia, was detected by immunohistochemistry. Protein expression levels of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) in the hippocampus were analyzed by an automatic protein expression analysis system. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect mRNA expression levels of M1 markers, JAK2/STAT3 pathway-related genes, and cytokines in hippocampal microglia in each group. ResultsCompared with the NC group, the MRS group exhibited depression-like behavior, with significantly decreased levels of neurotransmitters in the hippocampus (P<0.05, P<0.01), increased expression of Iba-1 (P<0.01), and elevated protein levels of JAK2 and STAT3 (P<0.05). The mRNA expression levels of CD68, CD11b, IL-1β, JAK2, and STAT3 were significantly increased (P<0.01), while IL-10 mRNA expression was significantly decreased (P<0.01). Compared with the MRS group, the XSF and minocycline groups showed some improvement in depression-like behavior. In these groups, the hippocampal neurotransmitter content was significantly increased (P<0.05, P<0.01), and Iba-1 expression was significantly decreased (P<0.01). The protein levels of JAK2 and STAT3 in the XSF group showed a downward trend. The mRNA expression levels of CD68, CD11b, JAK2, STAT3, and IL-1β in the hippocampus were significantly decreased in the XSF and minocycline groups (P<0.05, P<0.01), while IL-10 mRNA expression was significantly increased (P<0.05, P<0.01). ConclusionWenyang Jieyu prescription can regulate depression-like behavior in maternal-infant separation mice combined with secondary stress by inhibiting the polarization of hippocampal microglia to the M1 phenotype. The regulation of hippocampal microglia polarization by Wenyang Jieyu prescription may be associated with the JAK2/STAT3 pathway.
2.Effects of miR-204-3p inhibitor on epithelial-mesenchymal transition and silicosis fibrosis in silicon dioxide-induced alveolar epithelial cells
Fang CHEN ; Jing YU ; Wenxuan HU ; Yangyang PI ; Xi ZHANG ; Luning WANG ; Ping ZHAO ; Faxuan WANG
Journal of Environmental and Occupational Medicine 2025;42(5):622-629
Background The pathogenesis of silicosis has not been fully elucidated, and microRNAs (miRNA) may be involved in the occurrence and development of silicosis. Objective To investigate the effect of miR-204-3p inhibitor on the epithelial-mesenchymal transition (EMT) process and silicosis fibrosis in silicon dioxide dust-induced alveolar epithelial cells. Methods A co-culture model of macrophages and epithelial cells was established using a Transwell chamber. NR8383 macrophages were seeded into the upper chamber of the Transwell, and RLE-6TN cells were seeded into the lower chamber. After 24 h of culture, the medium in the lower chamber was discarded, washed three times with phosphate-buffered saline (PBS), and replaced with serum-free medium. The cells were divided into four groups: control group, silicosis group, miRNA NC group, and miR-204-3p inhibitor group. The lower chamber was transfected with miRNA NC for the miRNA NC group or the miR-204-3p inhibitor for the miR-204-3p inhibitor group. The lower chambers of the remaining two groups were added by equal amounts of serum-free medium. After 24 h, except for the control group that received an equal volume of serum-free medium, the upper chambers of the remaining three groups were treated with 800 μg·mL−1 silicon dioxide dust. Morphological changes in each group were observed under a microscope. The mRNA and protein expression levels of EMT-related factors, including α-smooth muscle actin (α-SMA), Vimentin, N-Cadherin, and E-Cadherin, were detected by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot. The mRNA and protein expression levels of fibrosis-related factors, including Collagen I, Collagen III, and Fibronectin, were also assessed by RT-qPCR and Western blot. The fluorescence expression intensities of α-SMA, N-Cadherin, and E-Cadherin were evaluated by immunofluorescence. Results The morphological observation revealed that RLE-6TN cells in the control group exhibited a regular oval shape. After treatment with silicon dioxide, the cells predominantly displayed a long spindle shape. Following the intervention with the miR-204-3p inhibitor, the number of long spindle-shaped cells increased, and the intercellular gaps widened. The RT-qPCR results showed that, compared with the control group, the silicosis group exhibited significantly higher relative mRNA expression levels of EMT-related markers (α-SMA, Vimentin, and N-Cadherin) (P<0.05), while the relative mRNA expression level of E-Cadherin was significantly reduced (P<0.05); the relative mRNA expression levels of fibrosis-related markers (Collagen I, Collagen III, and Fibronectin) were also significantly elevated (P<0.05). Compared with the miRNA NC group, the miR-204-3p inhibitor group showed significantly increased relative mRNA expression levels of α-SMA, Vimentin, and N-Cadherin (P<0.05), decreased E-Cadherin mPNA expression (P<0.05), and elevated mPNA expression of Collagen I, Collagen III, and Fibronectin (P<0.05). The Western blot analysis indicated that, compared with the control group, the silicosis group had significantly higher protein expression levels of α-SMA, Vimentin, and N-Cadherin (P<0.05), lower E-Cadherin protein expression (P<0.05), and increased protein expression of Collagen I, Collagen III, and Fibronectin (P<0.05). Compared with the miRNA NC group, the miR-204-3p inhibitor group exhibited significantly elevated protein expression levels of α-SMA, Vimentin, and N-Cadherin (P<0.05), reduced E-Cadherin expression (P<0.05), and increased protein expression of Collagen I, Collagen III, and Fibronectin (P<0.05). The immunofluorescence analysis demonstrated that, compared with the control group, the silicosis group showed enhanced fluorescence intensities of α-SMA and N-Cadherin and reduced fluorescence intensity of E-Cadherin. Compared with the miRNA NC group, the miR-204-3p inhibitor group exhibited increased fluorescence intensities of α-SMA and N-Cadherin and decreased fluorescence intensity of E-Cadherin. Conclusion The miR-204-3p inhibitor may exacerbate the EMT process and silicosis fibrosis in silicon dioxide-induced RLE-6TN cells. miR-204-3p plays a negative regulatory role in silicosis fibrosis.
3.Observation on the therapeutic effect of a modified Devine procedure with subcutaneous sliding fixation method for concealed penis.
Mohammed Abdulkarem AL-QAISI ; Hai-Fu TIAN ; Jia-Jin FENG ; Ke-Ming CHEN ; Jin ZHANG ; Yun-Shang TUO ; Xue-Hao WANG ; Bin-Cheng HUANG ; Muhammad Arslan Ul HASSAN ; Rui HE ; Guang-Yong LI
Asian Journal of Andrology 2025;27(4):470-474
To evaluate the therapeutic effect of a modified Devine procedure with a subcutaneous sliding fixation method for the treatment of congenital concealed penis, we retrospectively selected 45 patients with congenital concealed penises who were admitted to General Hospital of Ningxia Medical University (Yinchuan, China) between September 2020 and November 2023. In all cases, the penis was observed to be short, and retracting the skin at the base revealed a normal penile body, which immediately returned to its original position upon release. All patients underwent the modified Devine procedure with subcutaneous sliding fixation and completed a 12-week postoperative follow-up. A statistically significant increase in penile length was observed postoperatively, with the median length increasing from 4.0 (interquartile range [IQR]: 3.5-4.8; 95% confidence interval [CI]: 3.9-4.4) cm to 8.0 (IQR: 7.8-8.0; 95% CI: 7.7-7.9) cm, with P < 0.001. The parents were satisfied with the outcomes, including increased penile length, improved hygiene, and enhanced esthetics. Except for mild foreskin edema in all cases, no complications (such as infections, skin necrosis, or penile retraction) were observed. The edema was resolved within 4 weeks after the operation. This study demonstrates that the modified Devine procedure utilizing the subcutaneous sliding fixation method yields excellent outcomes with minimal postoperative complications, reduced penile retraction, and high satisfaction rates among patients and their families.
Humans
;
Male
;
Penis/abnormalities*
;
Retrospective Studies
;
Urologic Surgical Procedures, Male/methods*
;
Treatment Outcome
;
Child
;
Plastic Surgery Procedures/methods*
4.Three-dimensional finite element analysis of digital wire loop space maintainers for missing deciduous teeth.
Lijuan MA ; Yonghui TENG ; Yong WANG ; Yijiao ZHAO ; Xinyue ZHANG ; Qingzhao QIN ; Dong YIN
Journal of Peking University(Health Sciences) 2025;57(2):376-383
OBJECTIVE:
To establish a three-dimensional finite element model of a digital wire loop space maintainer for the mandible and primary tooth loss, in order to investigate the stress, deformation, and shear force experienced by patients with the loss of the second primary molar when wearing the wire loop space maintainer.
METHODS:
Cone beam computed tomography (CBCT) scans were performed on the patients to create a digital model of the mandible with the absence of the second primary molar using Mimics 21.0 software. A digital model integrating the crown's retention and the wire loop structure of the full crown and ring wire loop space maintainer was constructed using pediatric space maintainer design software, utilizing three different materials: cobalt-chromium alloy, polyether ether ketone (PEEK), and titanium alloy. In ANSYS Work Beach 2023 R2 software, vertical loads of 70 N, tilted 45° along the long axis of the tooth loads of 70 N, and a 10 N load on the surface of the wire loop were applied to the occlusal surfaces of models 46 and 84, simulating centric and lateral occlusions during chewing with the wire loop space maintainer in place. The stress states of the wire loop space maintainer and supporting teeth were analyzed.
RESULTS:
Under various loading conditions, the maximum principal stress of the ring wire loop space maintainer was significantly lower than that of the full crown. Stress contour maps indicated that the peak of the maximum principal stress occurred at the junction of the wire loop and crown structure, indicating that this area was more susceptible to fracture. The ring wire loop space maintainer made from PEEK material exhibited the lowest maximum shear stress on the internal organizational surfaces, with equivalent stresses of 23.18 MPa and 36.35 MPa for models 46 and 84, respectively. Stress contour maps demonstrated that the maximum stress on tooth 46 was located at its mesial, while the maximum stress on tooth 84 was situated near the root area on its distal, in contact with the wire loop space maintainer.
CONCLUSION
In cases of second primary molar loss, wearing the digital ring wire loop space maintainer can effectively distribute stress, and the ring wire loop space maintainer made from PEEK material reduces the stress experienced by supporting teeth to some extent, demonstrating its superiority in clinical application.
Finite Element Analysis
;
Humans
;
Tooth, Deciduous
;
Cone-Beam Computed Tomography
;
Space Maintenance, Orthodontic/methods*
;
Imaging, Three-Dimensional
;
Orthodontic Wires
;
Dental Stress Analysis
;
Mandible
;
Stress, Mechanical
5.Exploring urban versus rural disparities in atrial fibrillation: prevalence and management trends among elderly Chinese in a screening study.
Wei ZHANG ; Yi CHEN ; Lei-Xiao HU ; Jia-Hui XIA ; Xiao-Fei YE ; Wen-Yuan-Yue WANG ; Xin-Yu WANG ; Quan-Yong XIANG ; Qin TAN ; Xiao-Long WANG ; Xiao-Min YANG ; De-Chao ZHAO ; Xin CHEN ; Yan LI ; Ji-Guang WANG ; FOR THE IMPRESSION INVESTIGATORS AND COORDINATORS
Journal of Geriatric Cardiology 2025;22(2):246-254
BACKGROUND:
Atrial fibrillation (AF) is a common cardiac arrhythmia in the elderly. This study aimed to evaluate urban-rural disparities in its prevalence and management in elderly Chinese.
METHODS:
Consecutive participants aged ≥ 65 years attending outpatient clinics were enrolled for AF screening using handheld single-lead electrocardiogram (ECG) from April 2017 to December 2022. Each ECG rhythm strip was reviewed from the research team. AF or uninterpretable single-lead ECGs were referred for 12-lead ECG. Primary study outcome comparison was between rural and urban areas for the prevalence of AF. The Student's t-test was used to compare mean values of clinical characteristics between rural and urban participants, while the Pearson's chi-square test was used to compare between-group proportions. Multivariate stepwise logistic regression analysis was performed to estimate the association between AF and various patient characteristics.
RESULTS:
The 29,166 study participants included 13,253 men (45.4%) and had a mean age of 72.2 years. The 7073 rural participants differed significantly (P ≤ 0.02) from the 22,093 urban participants in several major characteristics, such as older age, greater body mass index, and so on. The overall prevalence of AF was 4.6% (n = 1347). AF was more prevalent in 7073 rural participants than 22,093 urban participants (5.6% vs. 4.3%, P < 0.01), before and after adjustment for age, body mass index, blood pressure, pulse rate, cigarette smoking, alcohol consumption and prior medical history. Multivariate logistic regression analysis identified overweight/obesity (OR = 1.35, 95% CI: 1.17-1.54) in urban areas and cigarette smoking (OR = 1.62, 95% CI: 1.20-2.17) and alcohol consumption (OR = 1.42, 95% CI: 1.04-1.93) in rural areas as specific risk factors for prevalent AF. In patients with known AF in urban areas (n = 781) and rural areas (n = 338), 60.6% and 45.9%, respectively, received AF treatment (P < 0.01), and only 22.4% and 17.2%, respectively, received anticoagulation therapy (P = 0.05).
CONCLUSIONS
In China, there are urban-rural disparities in AF in the elderly, with a higher prevalence and worse management in rural areas than urban areas. Our study findings provide insight for health policymakers to consider urban-rural disparity in the prevention and treatment of AF.
6.Relationship between psychological distress and psychosomatic symptoms in obsessive-compulsive disorder patients: the mediating role of anhedonia
Yuhan LI ; Fangqing SONG ; Shaoxia WANG ; Xueting ZHANG ; Yanrong WANG ; Jianqun FANG
Sichuan Mental Health 2025;38(3):217-222
BackgroundObsessive-compulsive disorder (OCD) is a common neuropsychiatric illness and is listed as one of the top ten disabling conditions causing loss of income and reduced quality of life. Psychological distress is an important cause of anhedonia in OCD patients, and is closely related to psychosomatic symptoms. Therefore, exploring the role of anhedonia in the relationship between psychological distress and psychosomatic symptoms is of great significance for optimizing clinical psychological treatment protocols for OCD patients. ObjectiveTo explore the role of anhedonia in the relationship between psychological distress and psychosomatic symptoms in OCD patients, with the aim of providing references for managing psychosomatic symptoms in patients. MethodsA total of 90 patients who met the diagnostic criteria for OCD according to the International Classification of Diseases, tenth edition (ICD-10), and who visited the Mental Health Center outpatient clinic of General Hospital of Ningxia Medical University from September 2023 to November 2024 were selected as the study objects. The instruments and techniques used for the evaluation were: Dimensional Anhedonia Rating Scale (DARS), 10-item Kessler Psychological Distress Scale (K10) and Psychosomatic Symptom Scale (PSSS). Model 4 of the Process for SPSS 26.0 was used to test the mediating role of anhedonia in the relationship between psychological distress and psychosomatic symptoms, with Bootstrapping used to assess the significance of mediating effect. ResultsA total of 84 patients (93.33%) completed the valid questionnaire. K10 score was positively correlated with PSSS total score, psychological symptom score and physical symptom score (r=0.559, 0.460, 0.551, P<0.01). K10 score was negatively correlated with DARS total score (r=-0.527, P<0.01). The total score of DARS was negatively correlated with PSSS total score (r=-0.497, P<0.01). Anhedonia mediated the relationship between psychological distress and psychosomatic symptoms, with an indirect effect value was 0.148 (95% CI: 0.042~0.278), accounting for 26.48% of the total effect. ConclusionPsychological distress can affect the psychosomatic symptoms in OCD patients both directly and indirectly via anhedonia.
7.Influence of chronic psychological stress during pregnancy on intestinal flora and eczema incidence of offspring rats
Chunyan WANG ; Ying GAO ; Deguang YANG ; Rui WANG ; Hongyu LI ; Ye LI ; Can LIU ; Suzhen GUAN
Journal of Environmental and Occupational Medicine 2025;42(8):962-970
Background Prenatal chronic psychological stress may increase the risk of allergic diseases in children, and eczema is the most common allergic disease in children, the pathogenesis of which is not yet fully understood. Objective To preliminarily clarify the changes in offspring intestinal flora after chronic stress exposure during pregnancy in rats that increases offspring immune imbalance and eczema susceptibility. Methods Thirty SPF-grade adult female SD rats were selected and randomly divided into a model group and a control group (n=15). Sixteen male rats were randomly divided into a model mating group and a control mating group (n=8). A 28-day chronic unpredictable mild stress (CUMS) model during pregnancy was established. On the 7th day of stress, male and female rats were caged in a ratio of 3:1. Blood samples were collected from female rats in each group via angular vein on the 1st day before stress, and on the 7th, 14th, 21st, and 28th days after stress. The content of plasma corticosterone during pregnancy was determined by enzyme-linked immunosorbent assay (ELISA). For the offspring rats, an eczema model was constructed using 2,4-dinitrochlorobenzene (DNCB). The number of scratching times of the offspring rats within 5 min was recorded. The offspring rats were divided into 4 groups: DNCB-CUMS group (MM), DNCB-control group (MC), solvent control-CUMS group (CM), and blank control group (CC), with 8 rats in each group. The eczema was induced once every 3 days, and the induction period was 12 d. The expression level of immunoglobulin E (IgE) in the serum of offspring rats after the eczema induction experiment were determined by ELISA. The concentrations of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-2 (IL-2), interleukin-4 (IL-4), and interleukin-13 (IL-13) in the serum were quantified by multi-parameter flow cytometry. The composition and abundance of intestinal microbiota in the feces of offspring rats were detected by 16S rRNA high-throughput sequencing technology. Results The plasma corticosterone concentrations in the model group were higher than those in the control group on the 7th and 21st days of stress (P<0.05). On the 14th and 21st days of stress, the 1% sucrose preference percentages of female rats in the model group were lower than that in the control group. On the 7th, 14th, and 21st days of stress, the horizontal movement scores of female rats in the model group and the vertical movement scores on the 7th and 14th days were lower than those in the control group (P<0.05). After 6, 9, and 12 d of model building, the scratching frequencies in the MC group and MM group were significantly higher than those in the CC group and CM group (P<0.05). Moreover, there were differences in the contents of cytokines including IFN-γ, IL-2, TNF-α, IL-4, IL-13, and IgE among the offspring rat groups (P<0.05). The CM group and MM group led to an increase in the contents of TNF-α, IL-4, IL-13, and IgE cytokines (P<0.05), while the MM group caused a decrease in the contents of IFN-γ and IL-2 (P<0.05). After the eczema induction experiment, the α-diversity analysis showed that the Simpson index and Shannon index in the CM were higher than those in the CC (P<0.05), indicating that CUMS during the pregnancy of female rats could increase the species abundance of their offspring. The abundances of Prevotella and Lactobacillus in the CM group decreased (P<0.05). Conclusion Intestinal dysbiosis in offspring due to chronic prenatal psychological stress, which may be one of the mechanisms linking maternal stress to immune imbalance and increased susceptibility to eczema in offspring.
8.Pharmaceutical care for a ulcerative colitis and ankylosing spondylitis patient who developed pustular psoriasis induced by infliximab
Xiaoling TUO ; Zhao WANG ; Shijie JU ; Shaoqi YANG ; Lijuan MA
China Pharmacy 2025;36(18):2312-2316
OBJECTIVE To provide a reference for pharmaceutical care in patients with ulcerative colitis (UC) and ankylosing spondylitis (AS) who developed pustular psoriasis induced by infliximab. METHODS Clinical pharmacists participated in the pharmaceutical care process of a patient with UC and AS who developed pustular psoriasis after using infliximab. The clinical pharmacists determined, using Naranjo’s Scale, that the correlation between the patient’s pustular psoriasis and infliximab was “likely”. Regarding the patient’s development of pustular psoriasis after using infliximab, the clinical pharmacists recommended discontinuing infliximab and switching to Upadacitinib extended-release tablets. For the patient’s skin allergic reaction after using upadacitinib, the clinical pharmacists advised continuing the use of upadacitinib and closely monitoring any potential adverse reactions during the treatment period. RESULTS The clinicians adopted the clinical pharmacists’ recommendation. Following the treatment, the patient’s symptoms were significantly alleviated, and the patient was discharged with medication. The follow-up after discharge showed that the treatment was effective and well-tolerated. CONCLUSIONS The clinical pharmacists analyzed the causal relationship between infliximab and pustular psoriasis. Through pharmaceutical care measures such as dynamic monitoring of skin lesions, evaluation of treatment responses, and optimization of drug regimens, they assisted the physicians in formulating an individualized medication plan, ensuring the safety and efficacy of the patient’s medication use.
9.Total Flavonoids from Cuscutae Semen Inhibit Depression in CUMS Mice via UCP2/TXNIP/NLRP3 Signaling Pathway
Andong SONG ; Guohua LI ; Bo YUAN ; Menghui JIA ; Zhantao LI ; Xiaoli WANG ; Long WANG ; Huiling FU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):109-119
ObjectiveTo investigate the antidepressant effects and mechanisms of total flavonoids from Cuscutae Semen (TFCC) in the mouse model of chronic unpredictable mild stress (CUMS). MethodsFifty male 4-week-old ICR mice were randomized into five groups (n=10 per group): blank control, model, Cuscutae Semen decoction (10.2 g·kg-1·d-1), paroxetine (2.6 mg·kg-1·d-1), and TFCC (173.2 mg·kg-1·d-1). The other groups except the blank control group underwent chronic unpredictable mild stress (CUMS) for 4 weeks. Behavioral assessments were conducted post-modeling. Then, the model group received distilled water (10 mL·kg-1·d-1), while treatment groups were administrated with respective agents via oral gavage (10 mL·kg-1) for 4 weeks. Depression-like behaviors were evaluated by the sucrose preference test (SPT), forced swimming test (FST), and tail suspension test (TST). Hippocampal neuronal morphology was observed via hematoxylin-eosin staining, and apoptosis in the brain tissue was assessed via terminal- deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). Enzyme-linked immunosorbent assay (ELISA) was employed to measure the hippocampal levels of inflammatory cytokines [interleukin (IL)-1β, IL-6, and TNF-α)] and neurotransmitters [5-hydroxytryptamine (5-HT), dopamine (DA), and brain-derived neurotrophic factor (BDNF)], while the reactive oxygen species (ROS) levels were quantified via the DCFH-DA probe. Real-time PCR was performed to measure the mRNA levels of NOD-like receptor protein 3 (NLRP3), apoptosis-associated Speck-like protein containing a CARD (ASC), cysteinyl aspartate-specific proteinase-1 (Caspase-1), IL-1β, and inducible nitric oxide synthase (iNOS). Western blot was employed to evaluate the protein levels of NLRP3, ASC, Caspase-1, uncoupling protein 2 (UCP2), and thioredoxin-interacting protein (TXNIP). ResultsCompared with the blank control group, the model group exhibited weight loss (P<0.01), reduced sucrose preference (P<0.01), prolonged immobility time in FST and TST (P<0.01), neuron disarrangement with nuclear pyknosis in hippocampal CA3 region, increased apoptosis in the brain tissue, elevated levels of IL-1β, IL-6, and TNF-α (P<0.01), declined levels of 5-HT, DA, and BDNF (P<0.01), increased ROS accumulation (P<0.01), upregulated mRNA levels of NLRP3, ASC, Caspase-1, IL-1β, and iNOS (P<0.01), down-regulated protein level of UCP2 (P<0.01), and up-regulated protein levels of NLRP3, ASC, Caspase-1, and TXNIP (P<0.01). Compared with the model group, the interventions restored sucrose preference (P<0.01), shortened immobility time (P<0.01), repaired hippocampal neuronal structure, reduced apoptosis, lowered the levels of inflammatory cytokines (P<0.01), restored the levels of neurotransmitters (P<0.01), alleviated ROS accumulation (P<0.01), downregulated the mRNA levels of NLRP3, ASC, Caspase-1, IL-1β, and iNOS (P<0.01), upregulated the protein level of UCP2 (P<0.01), and reduced the protein levels of NLRP3, ASC, Caspase-1, and TXNIP (P<0.01). Moreover, TFCC outperformed Cuscutae Semen decoction in ameliorating depressive behaviors. TFCC excelled in neuronal repair, neurotransmitter regulation, anti-inflammatory effects, and modulation of the UCP2/TXNIP/NLRP3 pathway (P<0.05). ConclusionTFCC modulates the hippocampal UCP2/TXNIP/NLRP3 pathway to inhibit inflammasome activation, reduce oxidative stress, restore neurotransmitters, thus suppressing neuronal apoptosis and promoting the rearrangement and morphology recovery of hippocampal cells. It outperforms Cuscutae Semen decoction in the antidepressant efficacy.
10.Total Flavonoids from Cuscutae Semen Inhibit Depression in CUMS Mice via UCP2/TXNIP/NLRP3 Signaling Pathway
Andong SONG ; Guohua LI ; Bo YUAN ; Menghui JIA ; Zhantao LI ; Xiaoli WANG ; Long WANG ; Huiling FU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):109-119
ObjectiveTo investigate the antidepressant effects and mechanisms of total flavonoids from Cuscutae Semen (TFCC) in the mouse model of chronic unpredictable mild stress (CUMS). MethodsFifty male 4-week-old ICR mice were randomized into five groups (n=10 per group): blank control, model, Cuscutae Semen decoction (10.2 g·kg-1·d-1), paroxetine (2.6 mg·kg-1·d-1), and TFCC (173.2 mg·kg-1·d-1). The other groups except the blank control group underwent chronic unpredictable mild stress (CUMS) for 4 weeks. Behavioral assessments were conducted post-modeling. Then, the model group received distilled water (10 mL·kg-1·d-1), while treatment groups were administrated with respective agents via oral gavage (10 mL·kg-1) for 4 weeks. Depression-like behaviors were evaluated by the sucrose preference test (SPT), forced swimming test (FST), and tail suspension test (TST). Hippocampal neuronal morphology was observed via hematoxylin-eosin staining, and apoptosis in the brain tissue was assessed via terminal- deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). Enzyme-linked immunosorbent assay (ELISA) was employed to measure the hippocampal levels of inflammatory cytokines [interleukin (IL)-1β, IL-6, and TNF-α)] and neurotransmitters [5-hydroxytryptamine (5-HT), dopamine (DA), and brain-derived neurotrophic factor (BDNF)], while the reactive oxygen species (ROS) levels were quantified via the DCFH-DA probe. Real-time PCR was performed to measure the mRNA levels of NOD-like receptor protein 3 (NLRP3), apoptosis-associated Speck-like protein containing a CARD (ASC), cysteinyl aspartate-specific proteinase-1 (Caspase-1), IL-1β, and inducible nitric oxide synthase (iNOS). Western blot was employed to evaluate the protein levels of NLRP3, ASC, Caspase-1, uncoupling protein 2 (UCP2), and thioredoxin-interacting protein (TXNIP). ResultsCompared with the blank control group, the model group exhibited weight loss (P<0.01), reduced sucrose preference (P<0.01), prolonged immobility time in FST and TST (P<0.01), neuron disarrangement with nuclear pyknosis in hippocampal CA3 region, increased apoptosis in the brain tissue, elevated levels of IL-1β, IL-6, and TNF-α (P<0.01), declined levels of 5-HT, DA, and BDNF (P<0.01), increased ROS accumulation (P<0.01), upregulated mRNA levels of NLRP3, ASC, Caspase-1, IL-1β, and iNOS (P<0.01), down-regulated protein level of UCP2 (P<0.01), and up-regulated protein levels of NLRP3, ASC, Caspase-1, and TXNIP (P<0.01). Compared with the model group, the interventions restored sucrose preference (P<0.01), shortened immobility time (P<0.01), repaired hippocampal neuronal structure, reduced apoptosis, lowered the levels of inflammatory cytokines (P<0.01), restored the levels of neurotransmitters (P<0.01), alleviated ROS accumulation (P<0.01), downregulated the mRNA levels of NLRP3, ASC, Caspase-1, IL-1β, and iNOS (P<0.01), upregulated the protein level of UCP2 (P<0.01), and reduced the protein levels of NLRP3, ASC, Caspase-1, and TXNIP (P<0.01). Moreover, TFCC outperformed Cuscutae Semen decoction in ameliorating depressive behaviors. TFCC excelled in neuronal repair, neurotransmitter regulation, anti-inflammatory effects, and modulation of the UCP2/TXNIP/NLRP3 pathway (P<0.05). ConclusionTFCC modulates the hippocampal UCP2/TXNIP/NLRP3 pathway to inhibit inflammasome activation, reduce oxidative stress, restore neurotransmitters, thus suppressing neuronal apoptosis and promoting the rearrangement and morphology recovery of hippocampal cells. It outperforms Cuscutae Semen decoction in the antidepressant efficacy.

Result Analysis
Print
Save
E-mail