1.Effect of Xiaoqinglong Decoction (小青龙汤) on Th2 Immune Responses and Nasal Mucosal TSLP/OX40L Pathway in Allergic Rhinitis Model Rats
Yimeng CHEN ; Yuye CHEN ; Guangchun YU ; Bei CHEN ; Jianwei ZHANG ; Shanshan DING ; Xiaoting YANG ; Baifan YU ; Yating CAI ; Xuejuan LIN ; Mengting ZHANG
Journal of Traditional Chinese Medicine 2026;67(9):994-1002
ObjectiveTo explore the potential mechanism of Xiaoqinglong Decoction (小青龙汤, XD) in the treatment of allergic rhinitis. MethodsForty-five rats were randomly assigned to a control group, a model group, a loratadine group, low-, medium- and high-dose XD groups, and low-, medium- and high-dose Mahuang Decoction and Cang'erzi Powder (麻黄汤合苍耳子散, MDCP) groups. Except for the control group, rats were administered with ovalbumin (OVA) and aluminum hydroxide via intraperitoneal injection for 14 days to establish an allergic rhinitis model. After the 14th-day injection, nasal stimulation was continued with 20 μl of 10% OVA solution to maintain the model. Rats in the control group and the model group received 10 ml/(kg·d) of saline, whereas those in the loratadine group were administered with 0.9 mg/(kg·d) of loratadine. The low-, medium- and high-dose XD groups were administered XD at the dose of 2.7, 5.4, and 10.8 g/(kg·d), respectively. The low-, medium- and high-dose MDCP groups were administered MDCP at the dose of 2.43, 4.86, and 9.72 g/(kg·d), respectively. All treatments were administered by gavage once daily for 7 consecutive days. One hour after the final gavage, nasal symptom scores were recorded for all group of rats. The next day, serum levels of immunoglobulin E (IgE), interleukin-4 (IL-4), and interleukin-13 (IL-13) were measured. HE staining was used to observe the pathological morphology of the nasal mucosal tissue. Quantitative reverse transcription PCR (RT-qPCR) and Western Blot were performed to assess mRNA and protein expression of thymic stromal lymphopoietin (TSLP) and OX40 ligand (OX40L) in the nasal mucosa. ResultsCompared to the control group, total nasal symptom score in the model group significantly increased (P<0.01). HE staining revealed disrupted and adhered cilia, thickened basement membranes, and extensive inflammatory cell infiltration in the nasal mucosa. Serum levels of total IgE, IL-4, and IL-13, as well as TSLP and OX40L mRNA and protein expression in the nasal mucosa, were significantly elevated in the model group (P<0.05 or P<0.01). Compared to the model group, the total nasal symptom scores in all drug intervention groups were significantly reduced; the serum total IgE levels in the loratadine group, the low- and medium-dose XD groups, and the low- and high-dose MDCP groups were significantly reduced; and the serum levels of IL-4 and IL-13 in the high-dose XD group and the high-dose MDCP group decreased (P<0.05 or P<0.01). Nasal mucosal structure was improved. Except for the low-dose MDCP group, all other intervention groups showed a significant reduction in TSLP and OX40L mRNA expression in the nasal mucosa (P<0.01). All doses of XD and the medium- and high-dose MDCP groups significantly decreased the protein levels of TSLP and OX40L (P<0.05). The medium-dose XD group exhibited more improvement of nasal symptom scores and greater suppression of expression of TSLP and OX40L mRNA, and TSLP protein levels compared to the loratadine group (P<0.05). ConclusionXD may protect nasal mucosa of rats and alleviate allergic rhinitis by suppressing the TSLP/OX40L pathway, thereby attenuating Th2-mediated immune responses.
2.Effect of Xiaoqinglong Decoction (小青龙汤) on Th2 Immune Responses and Nasal Mucosal TSLP/OX40L Pathway in Allergic Rhinitis Model Rats
Yimeng CHEN ; Yuye CHEN ; Guangchun YU ; Bei CHEN ; Jianwei ZHANG ; Shanshan DING ; Xiaoting YANG ; Baifan YU ; Yating CAI ; Xuejuan LIN ; Mengting ZHANG
Journal of Traditional Chinese Medicine 2026;67(9):994-1002
ObjectiveTo explore the potential mechanism of Xiaoqinglong Decoction (小青龙汤, XD) in the treatment of allergic rhinitis. MethodsForty-five rats were randomly assigned to a control group, a model group, a loratadine group, low-, medium- and high-dose XD groups, and low-, medium- and high-dose Mahuang Decoction and Cang'erzi Powder (麻黄汤合苍耳子散, MDCP) groups. Except for the control group, rats were administered with ovalbumin (OVA) and aluminum hydroxide via intraperitoneal injection for 14 days to establish an allergic rhinitis model. After the 14th-day injection, nasal stimulation was continued with 20 μl of 10% OVA solution to maintain the model. Rats in the control group and the model group received 10 ml/(kg·d) of saline, whereas those in the loratadine group were administered with 0.9 mg/(kg·d) of loratadine. The low-, medium- and high-dose XD groups were administered XD at the dose of 2.7, 5.4, and 10.8 g/(kg·d), respectively. The low-, medium- and high-dose MDCP groups were administered MDCP at the dose of 2.43, 4.86, and 9.72 g/(kg·d), respectively. All treatments were administered by gavage once daily for 7 consecutive days. One hour after the final gavage, nasal symptom scores were recorded for all group of rats. The next day, serum levels of immunoglobulin E (IgE), interleukin-4 (IL-4), and interleukin-13 (IL-13) were measured. HE staining was used to observe the pathological morphology of the nasal mucosal tissue. Quantitative reverse transcription PCR (RT-qPCR) and Western Blot were performed to assess mRNA and protein expression of thymic stromal lymphopoietin (TSLP) and OX40 ligand (OX40L) in the nasal mucosa. ResultsCompared to the control group, total nasal symptom score in the model group significantly increased (P<0.01). HE staining revealed disrupted and adhered cilia, thickened basement membranes, and extensive inflammatory cell infiltration in the nasal mucosa. Serum levels of total IgE, IL-4, and IL-13, as well as TSLP and OX40L mRNA and protein expression in the nasal mucosa, were significantly elevated in the model group (P<0.05 or P<0.01). Compared to the model group, the total nasal symptom scores in all drug intervention groups were significantly reduced; the serum total IgE levels in the loratadine group, the low- and medium-dose XD groups, and the low- and high-dose MDCP groups were significantly reduced; and the serum levels of IL-4 and IL-13 in the high-dose XD group and the high-dose MDCP group decreased (P<0.05 or P<0.01). Nasal mucosal structure was improved. Except for the low-dose MDCP group, all other intervention groups showed a significant reduction in TSLP and OX40L mRNA expression in the nasal mucosa (P<0.01). All doses of XD and the medium- and high-dose MDCP groups significantly decreased the protein levels of TSLP and OX40L (P<0.05). The medium-dose XD group exhibited more improvement of nasal symptom scores and greater suppression of expression of TSLP and OX40L mRNA, and TSLP protein levels compared to the loratadine group (P<0.05). ConclusionXD may protect nasal mucosa of rats and alleviate allergic rhinitis by suppressing the TSLP/OX40L pathway, thereby attenuating Th2-mediated immune responses.
3.Study on the current status and pathway optimization of traditional Chinese medicine preparations record-filing management in medical institutions across different provinces
Chao LIN ; Chenjie SHU ; Chuchu WAN ; Yang DONG ; Mengting DI ; Huiying SHEN ; Bo ZHANG
China Pharmacy 2026;37(13):1673-1678
OBJECTIVE To provide scientific reference for perfecting the record-filing management policy of traditional Chinese medicine preparations formulated via traditional processes for medical applications (hereinafter referred to as “TCM preparations”) in medical institutions, and further promote the sound development of the research and record-filing work of such preparations. METHODS A literature review combined with cross-sectional research was carried out. We collected policy documents and preparation information related to the record-filing of TCM preparations issued by national and provincial drug administration authorities on official websites during 2018-2025. A comparative analysis was conducted on the implementation and revision of core policy documents for the registration management of TCM preparations across provinces, the scope of record-filing dosage forms, conditions for rejection of record-filing, and exemptions for registration materials. Statistical analysis on the quantity and dosage forms of record-filing preparations in each province was conducted by means of data induction and trend chart plotting, and targeted suggestions were put forward to optimize the management pathway of record-filing. RESULTS CONCLUSIONS There was obvious heterogeneity in record-filing policies among provinces. Twelve provinces refined the applicable dosage forms for record-filing, fifteen provinces supplemented conditions for rejection of record-filing (16 items in total), and nine provinces expanded the scope of material exemptions. The number of recorded preparations presented a striking regional imbalance:Qinghai had the largest quantity of 4 269 varieties, while Hainan only had 14 varieties, with a gap of more than 300 times. The recorded preparations were mainly traditional dosage forms including pills (6 928 varieties) and powders (4 360 varieties). Only 12 provinces formulated the provincial catalog for TCM preparations allocation. In most regions, preparation circulation was only permitted within medical consortia, leading to a low transformation rate of scientific and technological achievements of preparations. It is recommended to optimize the record-filing management pathway from three aspects: strengthening policy standardization while maintaining flexibility, streamlining record-filing procedures and documentary requirements, and reinforcing technical support and achievement transformation. These measures can reduce regional policy differences, improve work efficiency of record-filing, and advance the standardized development and clinical value transformation of hospital-made TCM preparations.
4.Association of adverse childhood experiences with psychopathology, sleep, and cognitive function in children: the mediating role of putamen volume
Mengting ZHANG ; Min XIE ; Jiashuo ZHANG ; Xiaoying MA ; Menghan WEI ; Yubing YIN ; Yang CHEN ; Yulu WU ; Qiang WANG
Sichuan Mental Health 2026;39(3):263-273
BackgroundAdverse childhood experiences (ACEs) are strong predictors of psychopathology across the lifespan, exerting extensive adverse effects on physical and mental health during early development. While ACEs increase the risk of childhood psychopathology, sleep quality and impair cognitive function, the early neurobiological mechanisms mediating ACE-induced cognitive impairment remain unclear. ObjectiveTo explore the association between ACEs exposure and the risk of psychopathology, sleep disorders, and cognitive function, and to examine the mediating role of the putamen volume in the relationship between ACEs and cognitive function from a neurodevelopment perspective. MethodsData were obtained from the Adolescent Brain Cognitive Development (ABCD) study, comprising 10 572 children aged 9 to 10. Participants were categorized into five groups based on the cumulative score of ACEs reported by their parents and the children themselves: no-exposure group (0 types of ACEs), the one-exposure group, the two-exposure group, the three-exposure group, and the high-risk exposure group (≥ 4 types of ACEs). Logistic regression analysis was employed to evaluate the association between ACEs and psychopathological symptoms [T score of the Child Behavior Checklist (CBCL) ≥ 65]. Multiple linear regression analysis was ultilized to analyze the correlations between ACEs and the scores of the Sleep Disturbance Scale for Children (SDSC), the NIH Toolbox Cognition Battery (NIHTB-CB), as well as the multiple structures in the cerebral cortex and subcortex. The Bootstrap method was applied to test the mediating effect of the putamen volume between ACEs and neurocognitive function. ResultsAfter adjusting for confounders, ACEs cumulative score was correlated with children's psychopathological symptoms in a dose-response manner. Compared with the no-exposed group, the high-risk exposure group had a 2.08-fold (OR=2.080, 95% CI: 1.401–3.088) increased risk of internalizing problems and a 3.13-fold (OR=3.132, 95% CI: 1.703–5.760) increased risk of externalizing problems, and the risk of conduct problems was 4.68 times that of the no-exposed group (OR=4.681, 95% CI: 2.528–8.669). ACEs cumulative score positively predicted the total score of SDSC (β=0.080, 95% CI: 0.059–0.102), with relatively stronger predictive effects on sleep-wake transition disorder (β=0.086, 95% CI: 0.063–0.109) and sleep onset and maintenance disorder (β=0.066, 95% CI: 0.043–0.089). In terms of neurocognition and brain structure, ACEs cumulative score negatively predicted the overall cognitive composite score (β=-0.025, 95% CI: -0.050–-0.001), the crystallized cognitive composite score (β=-0.035, 95% CI: -0.060–-0.010), the volume of the left putamen nucleus (β=-0.025, 95% CI: -0.046– 0.003), and the volume of the right putamen nucleus (β=-0.023, 95% CI: -0.044– 0.003). The total putamen volume played a partial mediating role between ACEs and the overall cognitive composite score, the effect value was -0.002 (95% CI: -0.004–-0.001), accounting for 7.49% of the total effect. ConclusionACEs exposure may increase the risk of psychopathological and sleep disturbances in children and may impair neurocognitive function. Reduced putamen volume may serve a potential neurobiological pathway underlying the impact of ACEs on childhood cognition. [Funded by National Natural Science Foundation of China-Young Scientists Program (number, 82401763); Sichuan University West China Hospital Full-time Postdoctoral Research and Development Fund Project (number, 2023HXBH084)]
5.Study on the current status and pathway optimization of traditional Chinese medicine preparations record-filing management in medical institutions across different provinces
Chao LIN ; Chenjie SHU ; Chuchu WAN ; Yang DONG ; Mengting DI ; Huiying SHEN ; Bo ZHANG
China Pharmacy 2026;37(13):1673-1678
OBJECTIVE To provide scientific reference for perfecting the record-filing management policy of traditional Chinese medicine preparations formulated via traditional processes for medical applications (hereinafter referred to as “TCM preparations”) in medical institutions, and further promote the sound development of the research and record-filing work of such preparations. METHODS A literature review combined with cross-sectional research was carried out. We collected policy documents and preparation information related to the record-filing of TCM preparations issued by national and provincial drug administration authorities on official websites during 2018-2025. A comparative analysis was conducted on the implementation and revision of core policy documents for the registration management of TCM preparations across provinces, the scope of record-filing dosage forms, conditions for rejection of record-filing, and exemptions for registration materials. Statistical analysis on the quantity and dosage forms of record-filing preparations in each province was conducted by means of data induction and trend chart plotting, and targeted suggestions were put forward to optimize the management pathway of record-filing. RESULTS CONCLUSIONS There was obvious heterogeneity in record-filing policies among provinces. Twelve provinces refined the applicable dosage forms for record-filing, fifteen provinces supplemented conditions for rejection of record-filing (16 items in total), and nine provinces expanded the scope of material exemptions. The number of recorded preparations presented a striking regional imbalance:Qinghai had the largest quantity of 4 269 varieties, while Hainan only had 14 varieties, with a gap of more than 300 times. The recorded preparations were mainly traditional dosage forms including pills (6 928 varieties) and powders (4 360 varieties). Only 12 provinces formulated the provincial catalog for TCM preparations allocation. In most regions, preparation circulation was only permitted within medical consortia, leading to a low transformation rate of scientific and technological achievements of preparations. It is recommended to optimize the record-filing management pathway from three aspects: strengthening policy standardization while maintaining flexibility, streamlining record-filing procedures and documentary requirements, and reinforcing technical support and achievement transformation. These measures can reduce regional policy differences, improve work efficiency of record-filing, and advance the standardized development and clinical value transformation of hospital-made TCM preparations.
6.Mechanism of 1,25(OH)2D3 improving liver inflammation in a rat model of nonalcoholic steatohepatitis induced by choline-deficient L-amino acid-defined diet
Haiyang ZHU ; Jingshu CUI ; Liu YANG ; Mengting ZHOU ; Jian TONG ; Hongmei HAN
Journal of Clinical Hepatology 2025;41(2):254-262
ObjectiveTo investigate the effect of 1,25(OH)2D3 on the level of peroxisome proliferator-activated receptor-γ (PPAR-γ) in the liver, the phenotype of hepatic macrophages, and liver inflammation in a rat model of nonalcoholic steatohepatitis (NASH), as well as the mechanism of 1,25(OH)2D3 improving liver inflammation. MethodsAfter 1 week of adaptive feeding, 24 specific pathogen-free Wistar rats were randomly divided into normal group [choline-supplemented L-amino acid-defined (CSAA) diet], normal+1,25(OH)2D3 group [CSAA diet+1,25(OH)2D3], model group [choline-deficient L-amino acid-defined diet (CDAA) diet], and model+1,25(OH)2D3 group [CDAA diet+1,25(OH)2D3], with 6 rats in each group. The dose of 1,25(OH)2D3 was 5 μg/kg for intraperitoneal injection twice a week for 12 weeks. The serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured, liver histopathology was observed, and SAF score was assessed. M1 hepatic macrophages and M2 hepatic macrophages were measured to analyze in the change in the phenotype of hepatic macrophages, and ELISA was used to measure the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-4 (IL-4), and interleukin-10 (IL-10) in liver tissue, and qPCR was used to measure the mRNA level of PPAR-γ. The two-factor analysis of variance was use for comparison between groups, and the least significant difference t-test was used for further comparison; the Pearson method was used for correlation analysis. ResultsCompared with the normal group, the model rats with CDAA diet-induced NASH had significant increases in the serum levels of AST and ALT (P=0.019 and P<0.001), the SAF score of liver histopathology (P<0.001), the level of M1 hepatic macrophages (P<0.001), and the ratio of M1 and M2 hepatic macrophages (P<0.001), as well as a significant increase in the level of TNF-α (P<0.001) and a significant reduction in the level of IL-4 in liver tissue (P=0.025). The 1,25(OH)2D3 group had significant reductions in the serum levels of ALT (P<0.001), the SAF score of liver histopathology (P<0.001), the level of M1 hepatic macrophages (P<0.001), and the ratio of M1 and M2 hepatic macrophages (P=0.001), the level of IL-1β (P<0.001) and a significant increase in the level of M2 hepatic macrophages (P=0.017), the level of IL-10 (P=0.039), the level of IL-4 (P<0.001), the level of PPAR-γ (P=0.016). There were significant interactions between CDAA diet-induced NASH model and 1,25(OH)2D3 in serum the levels of AST and ALT (P=0.007 and P=0.008), the SAF scores of liver histopathology (P<0.001), the level of M1 hepatic macrophages (P<0.001), the level of M2 hepatic macrophages (P=0.008), the ratio of M1 and M2 of hepatic macrophages (P=0.005), the level of TNF-α (P<0.001), the level of IL-10 (P=0.038), the level of IL-4 (P<0.001) and the level of PPAR-γ (P=0.009). The correlation analysis showed that PPAR-γ was negatively correlated with the ratio of M1 and M2 hepatic macrophages (r=-0.415, P=0.044) and was positively correlated with M2 hepatic macrophages (r=0.435, P=0.033), IL-10 (r=0.433, P=0.035), and IL-4 (r=0.532, P=0.007). ConclusionThis study shows that 1,25(OH)2D3 improves liver inflammation in NASH by activating PPAR-γ to regulate the phenotypic transformation of hepatic macrophages.
7.The risk prediction models for anastomotic leakage after esophagectomy: A systematic review and meta-analysis
Yushuang SU ; Yan LI ; Hong GAO ; Zaichun PU ; Juan CHEN ; Mengting LIU ; Yaxie HE ; Bin HE ; Qin YANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(02):230-236
Objective To systematically evaluate the risk prediction models for anastomotic leakage (AL) in patients with esophageal cancer after surgery. Methods A computer-based search of PubMed, EMbase, Web of Science, Cochrane Library, Chinese Medical Journal Full-text Database, VIP, Wanfang, SinoMed and CNKI was conducted to collect studies on postoperative AL risk prediction model for esophageal cancer from their inception to October 1st, 2023. PROBAST tool was employed to evaluate the bias risk and applicability of the model, and Stata 15 software was utilized for meta-analysis. Results A total of 19 literatures were included covering 25 AL risk prediction models and 7373 patients. The area under the receiver operating characteristic curve (AUC) was 0.670-0.960. Among them, 23 prediction models had a good prediction performance (AUC>0.7); 13 models were tested for calibration of the model; 1 model was externally validated, and 10 models were internally validated. Meta-analysis showed that hypoproteinemia (OR=9.362), postoperative pulmonary complications (OR=7.427), poor incision healing (OR=5.330), anastomosis type (OR=2.965), preoperative history of thoracoabdominal surgery (OR=3.181), preoperative diabetes mellitus (OR=2.445), preoperative cardiovascular disease (OR=3.260), preoperative neoadjuvant therapy (OR=2.977), preoperative respiratory disease (OR=4.744), surgery method (OR=4.312), American Society of Anesthesiologists score (OR=2.424) were predictors for AL after esophageal cancer surgery. Conclusion At present, the prediction model of AL risk in patients with esophageal cancer after surgery is in the development stage, and the overall research quality needs to be improved.
8.Proton beam range verification algorithm for pixelated prompt gamma-ray imaging detector
Liwang YANG ; Haifeng OU ; Jinlong WANG ; Xiaoguang WU ; Ziyang HE ; Jian'an ZOU ; Yun ZHENG ; Congbo LI ; Shaoxiong GUAN ; Jing SHI ; Jinze LI ; Yunqiu LI ; Rui HONG ; Hao'en CHANG ; Mengting WANG ; Kaijie WEI
Chinese Journal of Medical Physics 2025;42(3):281-287
In proton therapy,prompt gamma-ray imaging is considered as one of the most promising methods for assessing proton beam range.Prompt gamma-ray imaging detector evaluates the proton beam range based on the prompt gamma-ray distribution obtained by the prompt gamma-ray imaging system,which enables high-precision measurement of the proton beam range.Herein a proton beam range verification algorithm is designed for the newly developed prototype of the range verification detector(pixelated prompt gamma-ray imaging detector),which verifies the range estimation accuracy of the prototype for different phantoms and different energies of homogeneous media through Monte Carlo simulation.The results show that the accuracy of the proton beam range verification algorithm is within 0.5 mm of the safety margin error of the Bragg peak,and the measurement accuracy is significantly improved with the increase of the number of protons,indicating that the prototype algorithm is feasible for proton beam range verification.
9.Research progress on the mechanism of regulating bilirubin metabolism by traditional Chinese medicines attributed to the liver meridian
Mengting JIANG ; Zicheng XIAN ; Yinmin ZHOU ; Chao CHEN ; Xue LI ; Ming YANG
Chinese Journal of Pharmacoepidemiology 2025;34(9):1084-1093
Bilirubin,as a major endogenous substance in the human body,plays anti-inflammatory,antioxidant,and cytoprotective roles within physiological ranges,serving a critical function in maintaining metabolic balance of endogenous substances.Bilirubin metabolism is a complex physiological process regulated by multiple factors,relying on UGT1A1 enzyme catalysis and transporter protein modulation to sustain substance homeostasis.Based on the theory of traditional Chinese medicine(TCM)channel tropism and the principle of visceral syndrome differentiation,liver-channel-tropic herbs can guide medications to specific viscera and meridians,exerting targeted therapeutic effects.These herbs regulate bilirubin metabolic disorders through multi-target mechanisms,including upregulating UGT1A1 enzyme activity to promote bilirubin conjugation,modulating MRP2/OATP expression to enhance bilirubin transport,attenuating oxidative stress to reduce hepatocyte damage,inhibiting inflammatory cytokines to restore metabolic enzyme activity,activating CAR signaling pathways to regulate bile acid homeostasis.This review summarizes the mechanisms by which TCM regulates bilirubin metabolism,focuses on the role of liver meridian-targeting TCM to provide a basis for its rational clinical use,and studies the effects of liver meridian-targeting TCM on bilirubin metabolism from its core mechanisms to guide its rational use and provide new ideas for the research and development of traditional Chinese medicine.This review summarizes the mechanisms by which TCM regulates bilirubin metabolism,focusing on the actions of herbs that enter the liver meridian.Starting from the core mechanisms,it explores how liver meridian-entering herbs significantly impact bilirubin metabolism.Some of these herbs demonstrate dual-directional regulatory effects on bilirubin metabolism.This understanding guides their rational clinical use,provides novel ideas for TCM research and development,and promotes the modernization of TCM studies.
10.2,6-dimethoxy-1,4-benzoquinone alleviates dextran sulfate sodium-induced ulcerative colitis in mice by suppressing NLRP3 inflammasome activation.
Chenfei LIU ; Wei ZHANG ; Yao ZENG ; Yan LIANG ; Mengting WANG ; Mingfang ZHANG ; Xinyuan LI ; Fengchao WANG ; Yanqing YANG
Journal of Southern Medical University 2025;45(8):1654-1662
OBJECTIVES:
To investigate the therapeutic mechanism of 2,6-dimethoxy-1,4-benzoquinone (DMQ) for alleviating dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice.
METHODS:
Eighteen male C57BL/6J mice were equally randomized into control group, DSS group and DMQ treatment group. In DSS and DMQ groups, the mice were treated with DSS in drinking water to induce UC, and received intraperitoneal injections of sterile PBS or DMQ (20 mg/kg) during modeling. The changes in body weight, disease activity index (DAI), colon length, spleen weight, and colon histological scores of the mice were examined, and the percentages of Th17 and IFN-γ+ CD8+ T cells in the mesenteric lymph nodes and spleen were analyzed using flow cytometry. The expressions of tight junction proteins (Occludin and ZO-1), proteins associated with inflammasome activation (caspase-1 and p20), IL-1β and TNF-α in the colon tissues were detected using Western blotting or ELISA. In the cell experiment, mouse bone marrow-derived macrophages (BMDMs) primed with lipopolysaccharide (LPS) were treated with DMQ, followed by stmulation with nigericin to activate the classical NLRP3 inflammasome pathway. In cultured human peripheral blood mononuclear cells (PBMCs) treated with either LPS alone or LPS plus nigericin, the effects of DMQ on inflammasome activation, pyroptosis, and cytokine release were evaluated via Western blotting, ELISA, and flow cytometry.
RESULTS:
In DSS-treated mice, DMQ treatment significantly alleviated DSS-induced body weight loss, colon shortening, spleen enlargement, and colon inflammation. The DMQ-treated mice showed significantly reduced percentages of Th17 cells and IFN-γ+ CD8+ T cells in the mesenteric lymph nodes and spleen, with increased occludin and ZO-1 expressions and decreased caspase-1 expression in the colon tissue. DMQ obviously inhibited classical NLRP3 inflammasome activation in mouse BMDMs and both the classical and alternative pathways of NLRP3 activation in human PBMCs, causing also suppression of caspase-1-dependent pyroptosis.
CONCLUSIONS
DMQ ameliorates DSS-induced UC in mice by inhibiting NLRP3 inflammasome activation.
Animals
;
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*
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Mice, Inbred C57BL
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Colitis, Ulcerative/metabolism*
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Dextran Sulfate/adverse effects*
;
Male
;
Inflammasomes/metabolism*
;
Mice
;
Benzoquinones/therapeutic use*
;
Th17 Cells
;
Caspase 1/metabolism*

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