1.Analysis of the current status of red blood cell transfusion in very preterm infants from Chinese Neonatal Network in 2022
Yan MO ; Aimin QIAN ; Ruimiao BAI ; Shujuan LI ; Xiaoqing YU ; Jin WANG ; K. Shoo LEE ; Siyuan JIANG ; Qiufen WEI ; Wenhao ZHOU
Chinese Journal of Pediatrics 2025;63(1):55-61
Objective:To analyze the current status of red blood cell transfusion in very preterm infants (VPI) (gestational age at birth <32 weeks) from Chinese Neonatal Network (CHNN) in 2022.Methods:This cross-sectional study was based on the CHNN VPI cohort. It included 6 985 VPI admitted to CHNN 89 participating centers within 24 hours after birth in 2022. VPI with major congenital anomalies or those transferred to non-CHNN centers for treatment or discharged against medical advice were excluded. VPI were categorized based on whether they received red blood cell transfusions, their gestational age at birth, the type of respiratory support received during transfusion, and whether the pre-transfusion hemoglobin levels exceeded the thresholds. General characteristics, red blood cell transfusion rates, number of transfusions, timing of the first transfusion, and pre-transfusion hemoglobin levels were compared among different groups. The incidence of adverse outcomes between the group of VPI who received transfusions above the threshold and those who received transfusions below the threshold were compared. Comparison among different groups was conducted using χ2 tests, Kruskal-Wallis H tests, Mann-Whitney U test, and so on. Trends by gestational age at birth were evaluated by Cochran-Armitage tests and Jonckheere-Terpstra tests for trend. Results:Among the 6 985 VPI, 3 865 cases(55.3%) were male, with a gestational age at birth of 30.0 (28.6, 31.0) weeks and a birth weight of (1 302±321) g. Overall, 3 617 cases (51.8%) received red blood cell transfusion, while 3 368 cases (48.2%) did not. The red blood cell transfusion rate was 51.8% (3 617/6 985), with rates of 77.7% (893/1 150) for those born before 28 weeks gestational age and 46.7% (2 724/5 835) for those born between 28 and 31 weeks gestational age. A total of 9 616 times red blood cell transfusions were administered to 3 617 VPI, with 632 times missing pre-transfusion hemoglobin data, and 8 984 times included in the analysis. Of the red blood cell transfusions, 25.6% (2 459/9 616) were administered when invasive respiratory support was required, 51.3% (4 934/9 616) were receiving non-invasive respiratory support, while 23.1% (2 223/9, 616) were given when no respiratory support was needed. Compared to the non-transfusion group, the red blood cell transfusion group had a higher rate of pregnancy-induced hypertension in mothers, lower rates of born via cesarean section and mother′s antenatal steroid administration, smaller gestational age, lower birth weight, a higher proportion of small-for-gestational-age, multiple births, and proportions of Apgar score at the 5 th minute after birth ≤3 (all P<0.05). They were also less likely to be female, born in hospital or undergo delayed cord clamping (all P<0.01). Additionally, higher transport risk index of physiologic stability score at admission were observed in the red blood cell transfusion group ( P<0.001). The number of red blood cell transfusion was 2 (1, 3) times, with the first transfusion occurring at an age of 18 (8, 29) days, and a pre-transfusion hemoglobin level of 97 (86, 109) g/L. For VPI ≤7 days of age, the pre-transfusion hemoglobin levels for invasive respiratory support, non-invasive respiratory support, or no respiratory support, respectively, with no statistically significant differences between groups ( H=5.59, P=0.061). For VPI aged 8 to 21 days and≥22 days, the levels with statistically differences between groups (both P<0.01). Red blood cell transfusions above recommended thresholds were observed in all respiratory support categories at different stages of life, with the highest prevalence in infants aged 8 to 21 days and≥22 days who did not require respiratory support, at 90.1% (264/273) and 91.1%(1 578/1 732), respectively. The rate of necrotizing enterocolitis was higher in the above-threshold group ( χ2=10.59, P=0.001), and the duration of hospital stay was longer in the above-threshold group ( Z=4.67, P<0.001) compared to the below-threshold group. Conclusions:In 2022, the red blood cell transfusion rate was relatively high among VPI from CHNN. Pre-transfusion hemoglobin levels frequently exceeded recommended transfusion thresholds.
2.Characteristics analysis of pediatric medicines with priority review and approval for marketing in China
Haoyu YANG ; Kan TIAN ; Xue YOU ; Hongwei DAN ; Qian WANG ; Xiaoyong YU
China Pharmacy 2025;36(5):519-523
OBJECTIVE To analyze the characteristics of pediatric medicines with priority review and approval for marketing in China, providing a reference for promoting enterprise R&D and production, as well as improving the supply guarantee mechanism for pediatric medicines. METHODS Based on publicly available data sources such as List of Approved Information for Pediatric Medications Subject to Priority Review and Approval, Pharnexcloud biomedical database, and National Medical Insurance Drug Directory, this study conducted a comprehensive analysis of the main characteristics of pediatric medicines with priority review and approval for marketing. RESULTS As of June 30, 2024, a total of 68 pediatric medicines had been approved through the priority review and approval process, covering 12 therapeutic areas, with oral dosage forms accounting for 64.71%. The median time from application to inclusion in priority review was 35.50 days, with an average of 41.69 days. The median time from inclusion in priority review to market approval was 1.24 years, with an average of 1.42 years. This included 12 domestic new medicines, 21 domestic generic medicines, 35 imported medicines, as well as 29 pediatric-specific medicines and 21 orphan medicines. Additionally, 31 of these medicines had been included in the medical insurance catalog, representing a proportion of 45.59%. CONCLUSIONS Currently, a trend of differentiated competition is emerging between domestic and imported pediatric medicines. The therapeutic areas for pediatric medicines are continuously expanding, and the dosage forms are becoming more tailored to children’s needs. However, there are still issues such as slow progress in new medicine development, insufficient stability in the medicine review and approval process, and a need to increase the proportion of medicines included in medical insurance.
3.Effect of wogonin on nerve injury in rats with diabetic cerebral infarction
Huanhuan WANG ; Panpan LIANG ; Jinshui YANG ; Shuxian JIA ; Jiajia ZHAO ; Yuanyuan CHEN ; Qian XUE ; Aixia SONG
Chinese Journal of Tissue Engineering Research 2025;29(11):2327-2333
BACKGROUND:Wogonin is a flavonoid extracted from the root of Scutellaria baicalensis.Previous studies have shown that baicalein has protective effects against cerebral ischemia-reperfusion injury,and can also reduce blood sugar and complications in diabetic mice,but its role and mechanism in diabetic cerebral infarction remain unclear. OBJECTIVE:To explore the effect of wogonin on nerve injury in rats with diabetic cerebral infarction and its mechanism. METHODS:Sprague-Dawley rats were randomly divided into six groups:control group,model group,low-dose wogonin group,medium-dose wogonin group,high-dose wogonin group,and high-dose wogonin+Ras homolog gene family member A(RhoA)activator group.Except for the control group,the other rats were established with diabetes and cerebral ischemia models using intraperitoneal injection of streptozotocin and middle cerebral artery occlusion.Low,medium-and high-dose wogonin groups were intragastrically given 10,20,40 mg/kg wogonin,respectively;high-dose wogonin+RhoA activator group was intragastrically given 40 mg/kg wogonin and intraperitoneally injected 10 mg/kg lysophosphatidic acid;control group and model group were given the same amount of normal saline once a day for 7 consecutive days.Rats in each group were evaluated for neurological deficits and their blood glucose levels were measured after the last dose.TTC staining was applied to detect the volume of cerebral infarction.Hematoxylin-eosin staining was applied to observe pathological changes in brain tissue.ELISA kit was applied to detect tumor necrosis factor-α,interleukin-6,malondialdehyde,and superoxide dismutase levels in brain tissue.Western blot was applied to detect the protein expression of RhoA and Rho-associated protein kinase(ROCK)2 in brain tissue. RESULTS AND CONCLUSION:Compared with the control group,the neuronal structure of rats in the model group was severely damaged,with cell necrosis and degeneration,the neurological deficit score,blood glucose level,and infarct volume were significantly elevated(P<0.05),the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue were significantly increased(P<0.05),and the superoxide dismutase level was decreased(P<0.05).Compared with the model group,the low-,medium-,and high-dose wogonin groups showed improved neuronal damage,reduced cell degeneration and necrosis,a significant reduction in neurological deficit score,blood glucose level,infarct volume,and the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue,and an increase in the superoxide dismutase level(P<0.05).Compared with the high-dose wogonin group,the high-dose wogonin+RhoA activator group significantly weakened the improvement in the above indexes of rats with diabetic cerebral infarction(P<0.05).To conclude,wogonin can improve the blood glucose level in rats with diabetic cerebral infarction,reduce cerebral infarction and nerve injury,and its mechanism may be related to the inhibition of RhoA/ROCK signaling pathway.
4.Recognition of breath odor map of benign and malignant pulmonary nodules and Traditional Chinese Medicine syndrome elements based on electronic nose combined with machine learning: An observational study in a single center
Shiyan TAN ; Qiong ZENG ; Hongxia XIANG ; Qian WANG ; Xi FU ; Jiawei HE ; Liting YOU ; Qiong MA ; Fengming YOU ; Yifeng REN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(02):185-193
Objective To explore the recognition capabilities of electronic nose combined with machine learning in identifying the breath odor map of benign and malignant pulmonary nodules and Traditional Chinese Medicine (TCM) syndrome elements. Methods The study design was a single-center observational study. General data and four diagnostic information were collected from 108 patients with pulmonary nodules admitted to the Department of Cardiothoracic Surgery of Hospital of Chengdu University of TCM from April 2023 to March 2024. The patients' TCM disease location and nature distribution characteristics were analyzed using the syndrome differentiation method. The Cyranose 320 electronic nose was used to collect the odor profiles of oral exhalation, and five machine learning algorithms including random forest (RF), K-nearest neighbor (KNN), logistic regression (LR), support vector machine (SVM), and eXtreme gradient boosting (XGBoost) were employed to identify the exhaled breath profiles of benign and malignant pulmonary nodules and different TCM syndromes. Results (1) The common disease locations in pulmonary nodules were ranked in descending order as liver, lung, and kidney; the common disease natures were ranked in descending order as Yin deficiency, phlegm, dampness, Qi stagnation, and blood deficiency. (2) The electronic nose combined with the RF algorithm had the best efficacy in identifying the exhaled breath profiles of benign and malignant pulmonary nodules, with an AUC of 0.91, accuracy of 86.36%, specificity of 75.00%, and sensitivity of 92.85%. (3) The electronic nose combined with RF, LR, or XGBoost algorithms could effectively identify the different TCM disease locations and natures of pulmonary nodules, with classification accuracy, specificity, and sensitivity generally exceeding 80.00%.Conclusion Electronic nose combined with machine learning not only has the potential capabilities to differentiate the benign and malignant pulmonary nodules, but also provides new technologies and methods for the objective diagnosis of TCM syndromes in pulmonary nodules.
5.Application of Recombinant Collagen in Biomedicine
Huan HU ; Hong ZHANG ; Jian WANG ; Li-Wen WANG ; Qian LIU ; Ning-Wen CHENG ; Xin-Yue ZHANG ; Yun-Lan LI
Progress in Biochemistry and Biophysics 2025;52(2):395-416
Collagen is a major structural protein in the matrix of animal cells and the most widely distributed and abundant functional protein in mammals. Collagen’s good biocompatibility, biodegradability and biological activity make it a very valuable biomaterial. According to the source of collagen, it can be broadly categorized into two types: one is animal collagen; the other is recombinant collagen. Animal collagen is mainly extracted and purified from animal connective tissues by chemical methods, such as acid, alkali and enzyme methods, etc. Recombinant collagen refers to collagen produced by gene splicing technology, where the amino acid sequence is first designed and improved according to one’s own needs, and the gene sequence of improved recombinant collagen is highly consistent with that of human beings, and then the designed gene sequence is cloned into the appropriate vector, and then transferred to the appropriate expression vector. The designed gene sequence is cloned into a suitable vector, and then transferred to a suitable expression system for full expression, and finally the target protein is obtained by extraction and purification technology. Recombinant collagen has excellent histocompatibility and water solubility, can be directly absorbed by the human body and participate in the construction of collagen, remodeling of the extracellular matrix, cell growth, wound healing and site filling, etc., which has demonstrated significant effects, and has become the focus of the development of modern biomedical materials. This paper firstly elaborates the structure, type, and tissue distribution of human collagen, as well as the associated genetic diseases of different types of collagen, then introduces the specific process of producing animal source collagen and recombinant collagen, explains the advantages of recombinant collagen production method, and then introduces the various systems of expressing recombinant collagen, as well as their advantages and disadvantages, and finally briefly introduces the application of animal collagen, focusing on the use of animal collagen in the development of biopharmaceutical materials. In terms of application, it focuses on the use of animal disease models exploring the application effects of recombinant collagen in wound hemostasis, wound repair, corneal therapy, female pelvic floor dysfunction (FPFD), vaginal atrophy (VA) and vaginal dryness, thin endometritis (TE), chronic endometritis (CE), bone tissue regeneration in vivo, cardiovascular diseases, breast cancer (BC) and anti-aging. The mechanism of action of recombinant collagen in the treatment of FPFD and CE was introduced, and the clinical application and curative effect of recombinant collagen in skin burn, skin wound, dermatitis, acne and menopausal urogenital syndrome (GSM) were summarized. From the exploratory studies and clinical applications, it is evident that recombinant collagen has demonstrated surprising effects in the treatment of all types of diseases, such as reducing inflammation, promoting cell proliferation, migration and adhesion, increasing collagen deposition, and remodeling the extracellular matrix. At the end of the review, the challenges faced by recombinant collagen are summarized: to develop new recombinant collagen types and dosage forms, to explore the mechanism of action of recombinant collagen, and to provide an outlook for the future development and application of recombinant collagen.
6.Construction and effectiveness evaluation of a closed-loop management system for dispensed oral drugs in the inpatient pharmacy based on SWOT analysis
Jia WANG ; Weihong GE ; Ruijuan XU ; Shanshan QIAN ; Xuemin SONG ; Xiangling SHENG ; Bin WU ; Li LI
China Pharmacy 2025;36(4):401-406
OBJECTIVE To improve the efficiency and quality of dispensed oral drug management in the inpatient pharmacy, and ensure the safety of drug use in patients. METHODS SWOT (strength, weakness, opportunity, threat) analysis method was used to analyze the internal strengths and weaknesses, as well as the external opportunities and threats in the construction of a closed-loop management system for dispensed oral drugs in the inpatient pharmacy of our hospital, and propose improvement strategies. RESULTS & CONCLUSIONS A refined, full-process, closed-loop traceability management system for dispensed oral drugs in the inpatient pharmacies was successfully established, which is traceable in origin, trackable in destination, and accountable in responsibility. After the application of this system, the registration rate of dispensed drug information and the correctness rate of registration content both reached 100%. The proportion of overdue drug varieties in the same period of 2024 decreased by 77.78% compared to March 2020, the inventory volume decreased by 29.50% compared to the first quarter of 2020, the per-bed medication volume decreased by 32.14% compared to the first quarter of 2020; the average workload per post in the same period of 2023 increased by 49.09% compared to 2019, the dispensing accuracy rate reached 100%, and the improvement rate of quality control problem increased by 25.25% compared to 2021. This system effectively improves the safety and accuracy of dispensed oral drug management in the inpatient pharmacy.
7.Study on quality evaluation of Mongolian medicine Sanzi powder:fingerprint,chemical pattern recognition and multi-component quantification analysis
Jun LI ; Rongjie LI ; Fengye ZHOU ; Qian ZHANG ; Wei ZHANG ; Bohan ZHANG ; Shu WANG ; Xitong ZHAO ; Jianping CHEN
China Pharmacy 2025;36(4):414-420
OBJECTIVE To establish fingerprint, chemical pattern recognition and multi-component quantification analysis of Sanzi powder, and evaluate its quality. METHODS HPLC method was adopted. The fingerprints of 15 batches of Sanzi powder were established by using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine (2012 edition). Cluster analysis, principal component analysis and orthogonal partial least squares-discriminant analysis were also conducted. The variable importance in projection (VIP) value greater than 1 was used as the index to screen the differential markers, and the contents of the differential markers were determined by the same HPLC method. RESULTS A total of 21 common peaks in the HPLC fingerprints of 15 batches of Sanzi powder were calibrated, and the similarities of them were 0.994- 0.999; 6 common peaks were identified, including gallic acid (peak 3), garminoside (peak 10), corilagin (peak 11), chebulinic acid (peak 16), ellagic acid (peak 18), crocin Ⅰ (peak 19). According to the results of cluster analysis, YKD2024LH005,No.YKD2023LH062) principal component analysis and orthogonal partial least squares-discriminant analysis, 15 batches of samples could be clustered into two categories: S1, S5, S7, S9, S14 were clustered into one category; S2-S4, S6, S8, S10-S13, S15 were clustered into one category. VIP values of 11 differential components such as corilagin, chebulinic acid and ellagic acid were higher than 1. Among 15 batches of samples, the contents of corilagin, chebulinic acid and ellagic acid ranged 2.667-5.152, 9.506- 13.522, 0.891-1.811 mg/g. CONCLUSIONS Established HPLC fingerprint and multi-component quantification analysis of Sanzi powder are rapid and simple, and can be used for quality evaluation of Sanzi powder by combining with chemical pattern recognition. Eleven components such as corilagin, chebulinic acid and ellagic acid are differential markers affecting the quality of Sanzi powder.
8.Effect of miR-130a-3p targeting PPAR-γ on epithelial-mesenchymal transition in silica-induced pulmonary fibrosis
Xiaohui HAO ; Qian LI ; Yixuan JIN ; Qinxin ZHANG ; Yudi WANG ; Fang YANG
Journal of Environmental and Occupational Medicine 2025;42(2):188-195
Background At present, the treatment of silicosis is still limited, and no method is available to cure the disease. miRNAs are involved in the process of fibrosis at the transcriptional level by directly degrading target gene mRNA or inhibiting its translation. However, how miR-130a-3p regulates silicosis fibrosis has not been fully elucidated yet. Objective To investigate whether miR-130a-3p promotes epithelial-mesenchymal transition (EMT) by inhibiting peroxisome proliferators-activated receptors gamma (PPAR-γ), thereby pro-moting the process of silicotic fibrosis. To identify effective new targets for the treatment of silicotic fibrosis. Methods (1) Animal experiments: C57BL/6J mice were intratracheally injected with a one-time dose of 10 mg silica suspension (dissolved in 100 μL saline) as positive lung exposure. A silicosis model group was established 28 d after the exposure. A control group was injected with the same amount of normal saline into the trachea. Hematoxylin-eosin staining and Sirius red staining were used to observe the pathological changes and collagen deposition in lung tissues respectively. Realtime fluorescence-based quantitative polymerase chain reaction (RT-qPCR) was used to assay the expression of miR-130a-3p and PPAR-γ mRNA in lung tissues. Western blotting was used to detect the protein expression of PPAR-γ, transforming growth factor (TGF)-β1, E-cadherin, α-smooth muscle actin (α-SMA), and Collagen Ⅰ in lung tissues. (2) Cells experiments: Mouse lung epithelial cells (MLE-12) were induced with 5 µg·L−1 TGF-β1 for different time (0, 12, 24, 48 h). RT-qPCR was used to detect the expression of miR-130a-3p and PPAR-γ mRNA in cells. The binding relationship between miR-130a-3p and PPAR-γ mRNA was verified by dual luciferase reporter gene assay. MLE-12 cells were stimulated by 5 µg·L−1 TGF-β1 after transfection of miR-130a-3p inhibitor, and Western blotting was used to measure the protein expression of PPAR-γ, E-cadherin, and α-SMA in the TGF-β1-induced cells. Results In the silicosis model group, the alveolar septum was widened and the pulmonary nodules were formed. The Sirius red staining collagen deposition in pulmonary nodules indicated that a silicosis fibrosis model was successfully established. The expressions of TGF-β1, α-SMA, and Collagen Ⅰ proteins were increased, and the expressions of E-cadherin and PPAR-γ proteins were decreased in lung tissues of the silicosis group, compared with the control group (P<0.05 or P<0.01). The expression of miR-130a-3p was increased and the expression of PPAR-γ mRNA was decreased in lung tissues of the silicosis model (P<0.01). The expression of miR-130a-3p was significantly increased, while the expression of PPAR-γ mRNA was decreased in the TGF-β1 induced MLE-12 cells (P<0.05 or P<0.01). The dual luciferase reporter assay showed a direct relationship between miR-130a-3p and PPAR-γ mRNA in MLE-12 cells. The transfection of miR-130a-3p inhibitor in the TGF-β1 induced MLE-12 cells inhibited the decrease of PPAR-γ and E-cadherin proteins, and the increase of α-SMA protein in the MLE-12 cells induced by TGF-β1 (P<0.05 or P<0.01). Conclusion miR-130a-3p promotes the development of silicosis fibrosis by targeting PPAR-γ to increase pulmonary EMT.
9.Compound Xishu Granules Inhibit Proliferation of Hepatocellular Carcinoma Cells by Regulating Ferroptosis
Yuan TIAN ; Yuxi WANG ; Zhen LIU ; Yuncheng MA ; Hongyu ZHU ; Xiaozhu WANG ; Qian LI ; Jian GAO ; Weiling WANG ; Wenhui XU ; Ting WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):37-45
ObjectiveTo study the mechanism of compound Xishu granules (CXG) in inhibiting the proliferation of hepatocellular carcinoma cells by regulating ferroptosis. MethodsThe transplanted tumor model of human Huh7 was established with nude mice and the successfully modeled mice were randomized into model, Fufang Banmao (0.21 g·kg-1), low-dose (1.87 g·kg-1) CXG, medium-dose (3.74 g·kg-1) CXG, and high-dose (7.49 g·kg-1) CXG groups. Mice were administrated with drinking water or CXG for 28 days, and the body weight and tumor volume were measured every 4 days. Hematoxylin-eosin staining was employed to observe the histopathological changes of tumors. The cell-counting kit-8 (CCK-8) was used to examine the survival rate of Huh7 cells treated with different concentrations (0, 31.25, 62.5, 125, 250, 500, 1 000 mg·L-1) of CXG for 24 h and 48 h. CA-AM, DCFH-DA, and C11-BODIPY581/591 fluorescent probes were used to determine the intracellular levels of ferrous ion (Fe2+), reactive oxygen species (ROS), and lipid peroxide (LPO), respectively. The colorimetric method was employed to measure the levels of glutathione (GSH) and superoxide dismutase (SOD). Western blot was employed to determine the protein levels of glutathione peroxidase 4 (GPX4), transferrin receptor 1 (TFR1), and ferritin heavy chain 1 (FTH1), respectively. ResultsIn the animal experiment, compared with the model group, the drug treatment groups showed reductions in the tumor volume from day 12 (P<0.01). After treatment, the Fufang Banmao and low-, medium-, and high-dose CXG groups had lower tumor volume, relative tumor volume, and tumor weight than the model group (P<0.05), with tumor inhibition rates of 48.99%, 79.93%, 91.38%, and 97.36%, respectively. Moreover, the CXG groups had lower tumor volume and relative tumor volume (P<0.05 in all the three dose groups) and lower tumor weight (P<0.05 in medium-dose and high-dose groups) than the Fufang Banmao group. Compared with the model group, the drug treatment groups showed reduced number of tumor cells, necrotic foci with karyopyknosis, nuclear fragmentation, and nucleolysis, and the high-dose CXG group showed an increase in the proportion of interstitial fibroblasts. In the cell experiment, compared with the blank group, CXG reduced the survival rate of Huh7 cells in a dose-dependent manner after incubation for 24 h and 48 h (P<0.05). Compared with the blank group, the RSL3 group and the low-, medium-, and high-dose CXG groups showed a decrease in the relative fluorescence intensity of CA-AM and increases in the fluorescence intensity of DCFH-DA and fluorescence ratio of C11-BODIPY581/591, which indicated elevations in the levels of Fe2+ (P<0.01), ROS (P<0.05), and LPO (P<0.01), respectively. Compared with the blank group, the RSL3 and low-, medium-, and high-dose CXG groups showed lowered levels of GSH and SOD (P<0.05). In addition, the RSL3 group and the medium- and high-dose CXG groups showed down-regulated expression of GPX4 and FTH1 (P<0.05), and the low- and high-dose CXG groups presented up-regulated expression of TFR1 (P<0.05). ConclusionCXG suppresses the proliferation of hepatocellular carcinoma cells by inducing ferroptosis via downregulating the GSH-GPX4 signaling axis and increasing intracellular Fe2+and LPO levels.
10.Rehmanniae Radix Iridoid Glycosides Protect Kidneys of Diabetic Mice by Regulating TGF-β1/Smads Signaling Pathway
Hongwei ZHANG ; Ming LIU ; Huisen WANG ; Wenjing GE ; Xuexia ZHANG ; Qian ZHOU ; Huani LI ; Suqin TANG ; Gengsheng LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):56-66
ObjectiveTo investigate the protective effect of Rehmanniae Radix iridoid glycosides (RIG) on the kidney tissue of streptozotocin (STZ)-induced diabetic mice and explore the underlying mechanism. MethodsTwelve of 72 male C57BL/6J mice were randomly selected as the normal group, and the remaining 60 mice were fed with a high-fat diet for six weeks combined with injection of 60 mg·kg-1 STZ for 4 days to model type 2 diabetes mellitus. The successfully modeled mice were randomized into model, metformin (250 mg·kg-1), catalpol (100 mg·kg-1), low-dose RIG (RIG-L, 200 mg·kg-1) and high-dose RIG (RIG-H, 400 mg·kg-1) groups (n=11). Mice in each group were administrated with corresponding drugs, while those in the normal group and model group were administrated with the same dose of distilled water by gavage once a day. After 8 weeks of intervention, an oral glucose tolerance test (OGTT) was performed, and the area under the curve (AUC) was calculated. After mice were sacrificed, both kidneys were collected. The body weight, kidney weight, and fasting blood glucose (FBG) were measured. Biochemical assays were performed to measure the serum levels of triglycerides (TG), total cholesterol (TC), serum creatinine (SCr), and blood urea nitrogen (BUN). Enzyme-linked immunosorbent assay (ELISA) was employed to determine the serum level of fasting insulin (FINS), and the insulin sensitivity index (ISI) and homeostatic model assessment for insulin resistance (HOMA-IR) were calculated. The pathological changes in kidneys of mice were observed by hematoxylin-eosin staining and Masson staining. The immunohistochemical method (IHC) was employed to assess the expression of interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), transforming growth factor-β1 (TGF-β1), and collagen-3 (ColⅢ) in the kidney tissue. The protein levels of TGF-β1, cell signal transduction molecule 3 (Smad3), matrix metalloproteinase-9 (MMP-9), and ColⅢ in kidneys of mice were determined by Western blot. ResultsCompared with the normal group, the model group showcased decreased body weight and ISI (P<0.01), increased kidney weight, FBG, AUC, FINS, HOMA-IR, TC, TG, SCr, and BUN (P<0.01), glomerular hypertrophy, capsular space narrowing, and collagen deposition in the kidney, up-regulated protein levels of IL-1, IL-6, TNF-α, TGF-β1, ColⅢ, and Smad3 (P<0.01), and down-regulated protein level of MMP-9 (P<0.01) in the kidney tissue. Compared with the model group, the treatment groups had no significant difference in the body weight and decreased kidney weight (P<0.05, P<0.01). The FBG level declined in the RIG-H group after treatment for 4-8 weeks and in the metformin, catalpol, and RIG-L groups after treatment for 6-8 weeks (P<0.01). The AUC in the RIG-L, RIG-H, and metformin groups decreased (P<0.05, P<0.01). The levels of TC, SCr, and BUN in the serum of mice in each treatment group became lowered (P<0.05, P<0.01). The level of TG declined in the RIG-L, RIG-H, and metformin groups (P<0.05, P<0.01). The serum level of FINS declined in the catalpol, RIG-L, and metformin groups (P<0.01). Compared with the model group, the treatment groups showed decreased HOMA-IR (P<0.01), increased ISI (P<0.01), alleviated pathological changes in the kidney tissue, and down-regulated expression of IL-1 and TGF-β1. In addition, the protein levels of IL-6, TNF-α, and ColⅢ in the RIG-H and metformin groups and IL-6 and TNF-α in the RIG-L group were down-regulated (P<0.05, P<0.01), and the protein levels of IL-6, TNF-α, and ColⅢ in the catalpol group and ColⅢ in the RIG-L group showed a decreasing trend without statistical difference. The protein levels of TGF-β1, Smad3, and ColⅢ in the RIG-H and metformin groups were down-regulated (P<0.01). Compared with that in the model group, the protein level of MMP-9 was up-regulated in each treatment group (P<0.01). ConclusionRIG can improve the renal structure and function of diabetic mice by regulating the TGF-β1/Smads signaling pathway.

Result Analysis
Print
Save
E-mail