1.Study on the variation patterns of corneal biomechanical parameters and binocular symmetry in children of different genders aged 8 to 16 years
Mei LI ; Biao WANG ; Fen ZHANG ; Yuting ZHANG ; Ze PEI ; Ning LU ; Feng CHANG
International Eye Science 2026;26(3):483-488
AIM: To investigate variation patterns of corneal biomechanical parameters and binocular symmetry among children of different genders aged 8-16 years.METHODS:A retrospective study was conducted, and children who underwent optometric examinations at the ophthalmology department of our hospital were enrolled between January 2022 and December 2024. Measurements included the flat keratometry(K1), steep keratometry(K2), and mean curvature(Km)of the anterior corneal surface, horizontal visible iris diameter(HVID), central corneal thickness(CCT), corneal endothelial cell density(CECD), average cell size(ACS), coefficient of variation(CV), and hexagonality(HEX). Corneal parameters and binocular differences were compared between genders and across age groups.RESULTS:A total of 621 children(1 242 eyes)were enrolled in this study, including 284 males(568 eyes), 337 females(674 eyes), 528 children aged 8-12 years(1 056 eyes), and 93 children aged 13-16 years(186 eyes). In children aged 8-16 years, the K1, K2, Km and CV of both eyes, as well as the interocular CCT differences in boys were significantly lower than those in girls(all P<0.05), while the HVID and HEX of both eyes, as well as the CCT of the left eye in boys were significantly higher than those in girls(all P<0.05). Children aged 8-12 years had significantly higher K1, Km, CECD and HEX in both eyes, and significantly lower ACS in both eyes than those aged 13-16 years(all P<0.05). K1, K2, Km, CECD and HEX in both eyes were negatively correlated with age(P<0.05); ACS in both eyes was positively correlated with age(P<0.001); K1 and Km of the right eye were positively correlated with the CECD of the right eye(P<0.05), and K1 and CCT of the left eye were positively correlated with the CECD of the left eye(P<0.05).CONCLUSION:Significant gender differences exist in corneal parameters among children aged 8 to 16 years, while binocular symmetry remained stable.
2.Effect Analysis of Different Interventions to Improve Neuroinflammation in The Treatment of Alzheimer’s Disease
Jiang-Hui SHAN ; Chao-Yang CHU ; Shi-Yu CHEN ; Zhi-Cheng LIN ; Yu-Yu ZHOU ; Tian-Yuan FANG ; Chu-Xia ZHANG ; Biao XIAO ; Kai XIE ; Qing-Juan WANG ; Zhi-Tao LIU ; Li-Ping LI
Progress in Biochemistry and Biophysics 2025;52(2):310-333
Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.
3.Working practices in eliminating the public health crisis caused by viral hepatitis in Hainan Province of China
Weihua LI ; Changfu XIONG ; Taifan CHEN ; Bin HE ; Dapeng YIN ; Xuexia ZENG ; Feng LIN ; Biyu CHEN ; Xiaomei ZENG ; Biao WU ; Juan JIANG ; Lu ZHONG ; Yuhui ZHANG
Journal of Clinical Hepatology 2025;41(2):228-233
In 2022, Hainan provincial government launched the project for the prevention and control of viral hepatitis with the goals of a hepatitis B screening rate of 90%, a diagnostic rate of 90%, and a treatment rate of 80% among people aged 18 years and above by the year 2025, and the main intervention measures include population-based prevention, case screening, antiviral therapy, and health management. As of December 31, 2024, a total of 6.875 million individuals in the general population had been screened for hepatitis B, with a screening rate of 95.6%. A total of 184 710 individuals with positive HBsAg were identified, among whom 156 772 were diagnosed through serological reexamination, resulting in a diagnostic rate of 84.9%. A total of 50 742 patients with chronic hepatitis B were identified, among whom 42 921 had hepatitis B-specific health records established for health management, with a file establishment rate of 84.6%. A total of 31 553 individuals received antiviral therapy, with a treatment rate of 62.2%. A total of 2.503 million individuals at a high risk of hepatitis C were screened, among whom 4 870 tested positive for HCV antibody and 3 858 underwent HCV RNA testing, resulting in a diagnostic rate of 79.2%, and 1 824 individuals with positive HCV RNA were identified, among whom 1 194 received antiviral therapy, with a treatment rate of 65.5%. In addition, 159 301 individuals with negative HBsAg and anti-HBs and an age of 20 — 40 years were inoculated with hepatitis B vaccine free of charge. Through the implementation of the project for the prevention and control of viral hepatitis, a large number of hepatitis patients have been identified, treated, and managed in the province within a short period of time, which significantly accelerates the efforts to eliminate the crisis of viral hepatitis.
4.Mechanism of Xielitang Against Ulcerative Colitis in Mice Based on "Intestinal Flora-bile Acid" Axis
Xiaotian WANG ; Yaning BIAO ; Yixin ZHANG ; Jian CHEN ; Ya GAO ; Yufang ZHANG ; Muqing ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):30-38
ObjectiveTo investigate the protective effect of Xielitang on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice and its possible mechanism. MethodsDSS was used to establish UC model. Sixty mice were randomly divided into a normal group, a model group, a sulfasalazine group (0.6 g·kg-1), and low-, medium-, and high-dose Xielitang groups (1.67, 3.34, 6.68 g·kg-1). After treatment for 42 d, the colon length was recorded, and the disease activity index (DAI) score was calculated. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10). Hematoxylin-eosin (HE) staining was used to observe the pathomorphological changes of colon. Western blot was used to detect the protein expression of farnesoid X receptor (FXR), small heterodimer partner (SHP), liver receptor homolog-1 (LRH-1), cholesterol 7α-hydroxylase (CYP7A1), and fibroblast growth factor receptor 4 (FGFR4) in liver and FXR, sodium-dependent bile acid transporter (ASBT), and fibroblast growth factor 15 (FGF15) in ileum. 16S rRNA sequencing was used to analyze the intestinal flora. Moreover, ultra-high performance liquid chromatography–tandem mass spectrometry was used to detect the bile acid content. ResultsCompared with the normal group, the model group showed significantly decreased colon length, IL-10 content, α-diversity index, abundance of Firmicutes and Lactobacillus, and content of deoxycholic acid (DCA) and lithocholic acid (LCA) (P<0.01), significantly increased DAI score, IL-6 and TNF-α content, abundance of Bacteroidetes, and the content of cholic acid (CA), chenodeoxycholic acid (CDCA), and taurocholic acid (TCA) (P<0.05, P<0.01), significantly down-regulated protein expression of FXR, SHP, and FGFR4 in liver and FXR, ASBT, and FGF15 in ileum (P<0.01), and significantly up-regulated protein expression of LRH-1 and CYP7A1 in liver (P<0.01). In addition, the structure of colonic mucosa was destroyed, and inflammatory cells infiltrated in the model group. Compared with the model group, Xielitang could significantly increase the colon length, IL-10 content, α-diversity index, the abundance of Firmicutes and Lactobacillus, and DCA and LCA content (P<0.05, P<0.01), decrease DAI score, abundance of Bacteroidetes, and the content of IL-6, TNF-α, CA, CDCA, and TCA (P<0.01), up-regulate the protein expression of FXR, SHP, and FGFR4 in liver and FXR, ASBT, and FGF15 in ileum (P<0.01), and down-regulate the protein expression of LRH-1 and CYP7A1 in liver (P<0.01). The pathological damage of colonic mucosa was obviously alleviated. ConclusionXielitang protects against UC probably by regulating the "intestinal microbiota-bile acid" axis, regulating intestinal flora imbalance, and maintaining bile acid homeostasis.
5.Clinical study on the treatment of chronic atrophic gastritis with spleen and stomach weakness syndrome by Piwei Peiyuan Pill combined with moxibustion
Kairui WU ; Yu YE ; Bei PEI ; Biao SONG ; Yi ZHANG ; Tingting LI ; Qi YANG ; Yun LIU ; Xuejun LI
Journal of Beijing University of Traditional Chinese Medicine 2025;48(2):280-290
Objective:
To determine the clinical efficacy and mechanism of Piwei Peiyuan Pill (PPP) combined with moxibustion for treating patients with chronic atrophic gastritis (CAG) with spleen and stomach weakness syndrome.
Methods:
Ninety-six CAG patients with spleen and stomach weakness syndrome who met the inclusion and exclusion criteria were enrolled at the Department of Spleen and Stomach Diseases of the Second Affiliated Hospital of Anhui University of Chinese Medicine from June 2022 to December 2023. The patients were randomly divided into a control, a Chinese medicine, and a combined group using a random number table method, with 32 cases in each group (two cases per group were excluded). The control group was treated with rabeprazole combined with folic acid tablets (both thrice daily), the Chinese medicine group was treated with PPP (8 g, thrice daily), and the combined group was treated with moxa stick moxibustion (once daily) on the basis of the Chinese medicine group for 12 consecutive weeks. Gastric mucosa atrophy in the three groups was observed before and after treatment. The gastric mucosal pathological score was evaluated. The Patient Reported Outcome (PRO) scale was used to evaluate the patients′ physical and mental health status and quality of life.An enzyme-linked immunosorbent assay was used to detect serum tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-4, IL-10, IL-37, and transforming growth factor (TGF)-β levels in each group. Real-time fluorescence PCR was used to detect the relative expression levels of signal transducer and activator of transcription 3 (STAT3) and mammalian target of rapamycin (mTOR) mRNA in each group. Western blotting was used to detect the relative expression levels of proteins related to the STAT3/mTOR signaling pathway, and the adverse drug reactions and events were recorded and compared.
Results:
There was no statistical difference in age, gender, disease duration, family history of gastrointestinal tumors, alcohol consumption history, and body mass index among the three groups of patients.The total therapeutic efficacy rates of the control, Chinese medicine, and combined groups in treating gastric mucosal atrophy were 66.67% (20/30), 86.67% (26/30), and 90.00% (27/30), respectively (P<0.05). Compared to before treatment, the pathological and PRO scale scores of gastric mucosa in each group decreased after treatment, and TNF-α, IL-1β, IL-37, and TGF-β levels decreased. The relative STAT3 and mTOR mRNA expression levels, as well as the relative STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels decreased (P<0.05), whereas the IL-4 and IL-10 levels increased (P<0.05). After treatment, compared to the control group, the pathological score of gastric mucosa, PRO scale score, TNF-α, IL-1β, IL-37, TGF-β content, relative STAT3 and mTOR mRNA expression levels, and relative STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels in the Chinese medicine and combined groups after treatment were reduced (P<0.05), whereas the IL-4 and IL-10 levels increased (P<0.05). After treatment, compared to the Chinese medicine group, the combined group showed a decrease in relative STAT3, mTOR mRNA expression levels, and STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels (P<0.05).
Conclusion
The combination of PPP and moxibustion may regulate the inflammatory mechanism of the body by inhibiting the abnormal activation of the STAT3/mTOR signaling pathway, upregulating related anti-inflammatory factor levels, downregulating pro-inflammatory factor expression, and increasing related repair factor expression, thereby promoting the recovery of atrophic gastric mucosa, reducing discomfort symptoms, and improving the physical and mental state of CAG patients with spleen and stomach weakness syndrome.
6.WW domain-containing ubiquitin E3 ligase 1 regulates immune infiltration in tumor microenvironment of ovarian cancer.
Xiaojuan GUO ; Ruijuan DU ; Liping CHEN ; Kelei GUO ; Biao ZHOU ; Hua BIAN ; Li HAN
Journal of Southern Medical University 2025;45(5):1063-1073
OBJECTIVES:
To explore the association of the expression of WW domain-containing ubiquitin E3 ligase 1 (WWP1) with immune infiltration in tumor microenvironment (TME) of ovarian cancer.
METHODS:
Ovarian cancer patient data from The Cancer Genome Atlas (TCGA) were used to analyze the association of WWP1 expression with patient prognosis. TISCH2 was utilized to analyze the changes in immune cell subtypes in TME of metastatic tumor and after chemotherapy. The impact of WWP1 on immune cell infiltration, somatic copy number alterations of WWP1 and evolution of immune cell subtypes was evaluated using TIMER and TIGER pseudo-time analysis. A deep learning model was used to analyze TCGA pathological images to investigate the effect of WWP1 on TME of ovarian cancer. RNA-seq analysis was conducted to identify the differentially expressed genes in WWP1-overexpressing SKOV3 cells and validate immune infiltration. Multicolor immunofluorescence assay was used to analyze the immune markers in SKOV3 and SKOV3/DDP cell xenografts in nude mice.
RESULTS:
The patients with high WWP1 expression levels had significantly lower overall survival rate (P=0.0012). High WWP1 expression levels and Stage IV disease were both associated with a poor prognosis (P<0.05). In metastatic ovarian cancer or after chemotherapy, the percentages of malignant tumor cells and tumor-associated fibroblasts increased in the TME, accompanied by elevated WWP1 levels. WWP1 expression level was positively correlated with pro-tumorigenic immunosuppressive cells (r=0.1323-0.3955, P<0.05) and negatively with tumor-inhibiting immune cells (r=-0.1949- -0.1333, P<0.05). Specific copy number alterations of WWP1 also influenced CD8+ T cell percentage and neutrophil infiltration levels in the TME. RNA-seq analysis of WWP1-overexpressing SKOV3 cells and immunofluorescence assay of the tumor-bearing mice yielded findings consistent with those of bioinformatics analysis.
CONCLUSIONS
WWP1 may serve as a prognostic biomarker and a potential target for immune regulation in the TME of ovarian cancer.
Female
;
Ovarian Neoplasms/genetics*
;
Humans
;
Ubiquitin-Protein Ligases/metabolism*
;
Tumor Microenvironment/immunology*
;
Animals
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Mice
;
Cell Line, Tumor
;
Mice, Nude
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Prognosis
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Gene Expression Regulation, Neoplastic
7.Effects of understory environmental factors on understory planting of medicinal plants.
Ding-Mei WEN ; Hong-Biao ZHANG ; Feng-Yuan QIN ; Chao-Qun XU ; Dou-Dou LI ; Bao-Lin GUO
China Journal of Chinese Materia Medica 2025;50(5):1164-1171
Understory planting of medicinal plants is a new planting mode that connects Chinese herbal medicine(CHM) with forest resources.The complex and variable understory environmental factors will inevitably affect the yield and quality of understory CHM.This research summarized the research progress on understory planting of medicinal plants based on forest types and environmental factors within the forest from the perspectives of understory light, air temperature and humidity, soil characteristics, and the interaction between crops within the forest.The results showed that the complex and variable light, temperature and humidity, and soil factors(such as fertility, acidity and alkalinity, and microorganisms) under the forest could affect the yield and quality of medicinal plants to varying degrees through physiological activities such as photosynthesis and respiration, resulting in a significant increase or decrease in yield and quality compared to open field cultivation.In addition, the competition or mutual benefit between different crops within the forest could lead to differences in the yield and quality of understory medicinal plants compared to open field cultivation.A reasonable combination of planting could achieve resource sharing and complementary advantages.Therefore, conducting systematic research on the effects of understory environmental factors on the yield and content of medicinal plants with different growth and development characteristics can provide theoretical guidance and technical references for formulating comprehensive strategies for understory planting of medicinal plants, such as selecting suitable medicinal plant varieties, optimizing planting density, and conducting reasonable forest management, thus contributing to the sustainable development and ecological protection of CHM.
Plants, Medicinal/growth & development*
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Forests
;
Soil/chemistry*
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Environment
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Ecosystem
;
Temperature
8.Identification of terpenoid synthases family in Perilla frutescens and functional analysis of germacrene D synthase.
Pei-Na ZHOU ; Zai-Biao ZHU ; Lei XIONG ; Ying ZHANG ; Peng CHEN ; Huang-Jin TONG ; Cheng-Hao FEI
China Journal of Chinese Materia Medica 2025;50(10):2658-2673
Based on whole-genome identification of the TPS gene family in Perilla frutescens and screening, cloning, bioinformatics, and expression analysis of the synthetic enzyme for the insect-resistant component germacrene D, this study lays the foundation for understanding the biological function of the TPS gene family and the insect resistance mechanism in P. frutescens. This study used bioinformatics tools to identify the TPS gene family of P. frutescens based on its whole genome and predicted the physicochemical properties, systematic classification, and promoter cis-elements of the proteins. The relative content of germacrene D was detected in both normal and insect-infested leaves of P. frutescens, and the germacrene D synthase was screened and isolated. Gene cloning, bioinformatics analysis, and expression profiling were then performed. The results showed that a total of 99 TPS genes were identified in the genome, which were classified into the TPS-a, TPS-b, TPS-c, TPS-e/f, and TPS-g subfamilies. Conserved motif analysis showed that the TPS in P. frutescens has conserved structural characteristics within the same subfamily. Promoter cis-element analysis predicted the presence of light-responsive elements, multiple hormone-responsive elements, and stress-responsive elements in the TPS family of P. frutescens. Transcriptome data revealed that most of the TPS genes in P. frutescens were highly expressed in the leaves. GC-MS analysis showed that the relative content of germacrene D significantly increased in insect-damaged leaves, suggesting that it may act as an insect-resistant component. The germacrene D synthase gene was screened through homologous protein binding gene expression and was found to belong to the TPS-a subfamily, encoding a 64.89 kDa protein. This protein was hydrophilic, lacked a transmembrane structure and signal peptide, and was predominantly expressed in leaves, with significantly higher expression in insect-damaged leaves compared to normal leaves. In vitro expression results showed that germacrene D synthase tended to form inclusion bodies. Molecular docking showed that farnesyl pyrophosphate(FPP) fell into the active pocket of the protein and interacted strongly with six active sites. This study provides a foundation for further research on the biological functions of the TPS gene family in P. frutescens and the molecular mechanisms underlying its insect resistance.
Perilla frutescens/chemistry*
;
Plant Proteins/chemistry*
;
Multigene Family
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Sesquiterpenes, Germacrane/metabolism*
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Alkyl and Aryl Transferases/chemistry*
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Phylogeny
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Gene Expression Regulation, Plant
9.Blood glucose-lowering mechanism of Poria aqueous extract by UPLC-Q-TOF-MS/MS combined with network pharmacology and experimental verification.
Dan-Dan ZHANG ; Wen-Biao WAN ; Qing YAO ; Fang LI ; Zi-Yin YAO ; Xiao-Chuan YE
China Journal of Chinese Materia Medica 2025;50(14):3980-3989
Ultra performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry/mass spectrometry(UPLC-Q-TOF-MS/MS), network pharmacology, and animal experiments were integrated o explore the blood glucose-lowering effects and mechanisms of Poria aqueous extract. Firstly, the active components of Poria aqueous extract were identified by UPLC-Q-TOF-MS/MS. Subsequently, network pharmacology was employed to predict the blood glucose-lowering components and mechanisms of Poria aqueous extract. Finally, a rat model of diabetes mellitus, 16S rDNA sequencing, and Western blot were employed to investigate the blood glucose-lowering effect and mechanism of Poria aqueous extract. A total of 39 triterpenoids were identified in the Poria aqueous extract, among them, 25-hydroxypachymic acid, 25α-hydroxytumulosic acid, 16α-hydroxytrametenolic acid, polyporenic acid C, and tumulosic acid may be the main active ingredients for treating diabetes. The Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis revealed that Poria might exert its therapeutic effects through multiple pathways such as NOD-like receptor signaling pathway, nuclear factor-kappa B(NF-κB) signaling pathway, and tumor necrosis factor(TNF) signaling pathway. The results of animal experiments demonstrated that Poria aqueous extract significantly reduced the levels of blood glucose and lipids and regulated the intestinal flora in diabetic rats. The main affected taxa included g_Escherichia-Shigella, g_Corynebacterium, g_Prevotella_9, g_Prevotellaceae_UCG-001, and g_Bacteroidota_unclassified. In addition, Poria aqueous extract lowered the levels of D-lactic acid and lipopolysaccharide, alleviated colonic mucosal damage, significantly down-regulated the protein levels of NOD-like receptor pyrin domain-containing protein 3(NLRP3), NF-κB, and TNF-α, and significantly up-regulated the protein levels of zonula occludens 1 and occludin in diabetic rates. Poria aqueous extract may play a role in treating diabetes mellitus by repairing the intestinal flora disturbance, protecting the intestinal barrier function, and inhibiting the NF-κB/NLRP3 signaling pathway. The results provide a scientific basis for clinical application and expansion of indications of Poria.
Animals
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Rats
;
Network Pharmacology
;
Tandem Mass Spectrometry
;
Male
;
Drugs, Chinese Herbal/pharmacology*
;
Chromatography, High Pressure Liquid
;
Blood Glucose/drug effects*
;
Rats, Sprague-Dawley
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Hypoglycemic Agents/administration & dosage*
;
Poria/chemistry*
;
Diabetes Mellitus, Experimental/metabolism*
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NF-kappa B/genetics*
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Gastrointestinal Microbiome/drug effects*
;
Humans
10.Danggui Shaoyaosan Regulates Nrf2/SLC7A11/GPX4 Signaling Pathway to Inhibit Ferroptosis in Rat Model of Non-alcoholic Fatty Liver Disease
Xinqiao CHU ; Yaning BIAO ; Ying GU ; Meng LI ; Tiantong JIANG ; Yuan DING ; Xiaping TAO ; Shaoli WANG ; Ziheng WEI ; Zhen LIU ; Yixin ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):35-42
ObjectiveTo investigate the effect of Danggui Shaoyaosan on ferroptosis in the rat model of non-alcoholic fatty liver disease (NAFLD) and explore the underlying mechanism based on the nuclear factor E2-related factor 2 (Nrf2)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway. MethodsThe sixty SD rats were randomly grouped as follows: control, model, Yishanfu (0.144 g·kg-1), and low-, medium-, and high-dose (2.44, 4.88, and 9.76 g·kg-1, respectively) Danggui Shaoyaosan. A high-fat diet was used to establish the rat model of NAFLD. After 12 weeks of modeling, rats were treated with corresponding agents for 4 weeks. Then, the body weight and liver weight were measured, and the liver index was calculated. At the same time, serum and liver samples were collected. The levels or activities of total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and Fe2+ in the serum and TC, TG, free fatty acids (FFA), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX), and Fe2+ in the liver were measured. Hematoxylin-eosin staining and oil red O staining were employed to observe the pathological changes in the liver. Immunofluorescence was used to assess the reactive oxygen species (ROS) content in the liver. Mitochondrial morphology was observed by transmission electron microscopy. The protein levels of Nrf2, SLC7A11, GPX4, transferrin receptor 1 (TFR1), and divalent metal transporter 1 (DMT1) in the liver were determined by Western blot. ResultsCompared with the control group, the model group showed increases in the body weight, liver weight, liver index, levels or activities of TC, TG, ALT, AST, and Fe2+ in the serum, levels of TC, TG, FFA, MDA, Fe2+, and ROS in the liver, and protein levels of TFR1 and DMT1 in the liver (P<0.01), and decreases in the activities of SOD, GPX and the protein levels of Nrf2, SLC7A11, and GPX4 in the liver (P<0.05, P<0.01). Meanwhile, the liver tissue in the model group presented steatosis, iron deposition, mitochondrial shrinkage, and blurred or swollen mitochondrial cristae. Compared with the model group, all doses of Danggui Shaoyaosan reduced the body weight, liver weight, liver index, levels or activities of TC, TG, ALT, AST, and Fe2+ in the serum, levels of TC, TG, FFA, MDA, Fe2+, and ROS in the liver, and protein levels of TFR1 and DMT1 in the liver (P<0.01), while increasing the activities of SOD and GPX and the protein levels of Nrf2, SLC7A11, and GPX4 in the liver (P<0.01). Furthermore, Danggui Shaoyaosan alleviated steatosis, iron deposition, and mitochondrial damage in the liver. ConclusionDanggui Shaoyaosan may inhibit lipid peroxidation and ferroptosis by activating the Nrf2/SLC7A11/GPX4 signaling pathway to treat NAFLD.


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