1.Analysis of Potential Active Components and Molecular Mechanism of Baoxin Granules Regulating Ferroptosis in Treatment of Heart Failure
Yu CHEN ; Maolin WANG ; Yun WANG ; Yifan ZHAO ; Jing XU ; Hongwei WU ; Fang WANG ; Xiaoang ZHAO ; Youming LI ; Jixiang TIAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):202-209
ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS), network pharmacology, molecular docking and cell experiments, the active ingredients, possible targets and molecular mechanisms of Baoxin granules(BXG) regulating ferroptosis in the treatment of heart failure(HF) were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components, the potential targets of BXG were predicted, and the HF-related targets and related genes of ferroptosis were retrieved at the same time, and the intersecting targets were obtained by Venn diagram. In addition, the protein-protein interaction(PPI) network and the component-target network were constructed, and the core components and core targets were obtained by topological analysis. Then Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis were performed on the core targets, and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model, and the protective effect of BXG on cells was investigated by detecting cell viability, cell survival rate and reactive oxygen species(ROS) level. The protein expression levels of signal transducer and activator of transcription 3(STAT3), phosphorylation(p)-STAT3 and glutathione peroxidase 4(GPX4) were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified, and network pharmacology obtained 27 potential targets of BXG for the treatment of HF, as well as 139 signaling pathways. BXG may act on core targets such as STAT3, tumor protein p53(TP53), epidermal growth factor receptor(EGFR), JUN and prostaglandin-endoperoxide synthase 2(PTGS2) through core components such as glabrolide and limonin, which in turn intervene in lipid and atherosclerosis, phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group, the cell viability and survival rate of the model group were significantly decreased, the level of ROS was significantly increased(P<0.01), the expression levels of STAT3, p-STAT3, p-STAT3/STAT3 and GPX4 proteins were significantly decreased(P<0.05, P<0.01). Compared with the model group, the cell viability and survival rate of the BXG group were significantly increased, the ROS level was significantly decreased(P<0.01), the STAT3, p-STAT3, p-STAT3/STAT3 and GPX4 protein levels were significantly increased(P<0.05, P<0.01). ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4, thus exerting a therapeutic effect on HF, and flavonoids may be the key components of this role.
2.Analysis of Potential Active Components and Molecular Mechanism of Baoxin Granules Regulating Ferroptosis in Treatment of Heart Failure
Yu CHEN ; Maolin WANG ; Yun WANG ; Yifan ZHAO ; Jing XU ; Hongwei WU ; Fang WANG ; Xiaoang ZHAO ; Youming LI ; Jixiang TIAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):202-209
ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS), network pharmacology, molecular docking and cell experiments, the active ingredients, possible targets and molecular mechanisms of Baoxin granules(BXG) regulating ferroptosis in the treatment of heart failure(HF) were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components, the potential targets of BXG were predicted, and the HF-related targets and related genes of ferroptosis were retrieved at the same time, and the intersecting targets were obtained by Venn diagram. In addition, the protein-protein interaction(PPI) network and the component-target network were constructed, and the core components and core targets were obtained by topological analysis. Then Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis were performed on the core targets, and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model, and the protective effect of BXG on cells was investigated by detecting cell viability, cell survival rate and reactive oxygen species(ROS) level. The protein expression levels of signal transducer and activator of transcription 3(STAT3), phosphorylation(p)-STAT3 and glutathione peroxidase 4(GPX4) were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified, and network pharmacology obtained 27 potential targets of BXG for the treatment of HF, as well as 139 signaling pathways. BXG may act on core targets such as STAT3, tumor protein p53(TP53), epidermal growth factor receptor(EGFR), JUN and prostaglandin-endoperoxide synthase 2(PTGS2) through core components such as glabrolide and limonin, which in turn intervene in lipid and atherosclerosis, phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group, the cell viability and survival rate of the model group were significantly decreased, the level of ROS was significantly increased(P<0.01), the expression levels of STAT3, p-STAT3, p-STAT3/STAT3 and GPX4 proteins were significantly decreased(P<0.05, P<0.01). Compared with the model group, the cell viability and survival rate of the BXG group were significantly increased, the ROS level was significantly decreased(P<0.01), the STAT3, p-STAT3, p-STAT3/STAT3 and GPX4 protein levels were significantly increased(P<0.05, P<0.01). ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4, thus exerting a therapeutic effect on HF, and flavonoids may be the key components of this role.
3.Research progress of nano drug delivery system based on metal-polyphenol network for the diagnosis and treatment of inflammatory diseases
Meng-jie ZHAO ; Xia-li ZHU ; Yi-jing LI ; Zi-ang WANG ; Yun-long ZHAO ; Gao-jian WEI ; Yu CHEN ; Sheng-nan HUANG
Acta Pharmaceutica Sinica 2025;60(2):323-336
Inflammatory diseases (IDs) are a general term of diseases characterized by chronic inflammation as the primary pathogenetic mechanism, which seriously affect the quality of patient′s life and cause significant social and medical burden. Current drugs for IDs include nonsteroidal anti-inflammatory drugs, corticosteroids, immunomodulators, biologics, and antioxidants, but these drugs may cause gastrointestinal side effects, induce or worsen infections, and cause non-response or intolerance. Given the outstanding performance of metal polyphenol network (MPN) in the fields of drug delivery, biomedical imaging, and catalytic therapy, its application in the diagnosis and treatment of IDs has attracted much attention and significant progress has been made. In this paper, we first provide an overview of the types of IDs and their generating mechanisms, then sort out and summarize the different forms of MPN in recent years, and finally discuss in detail the characteristics of MPN and their latest research progress in the diagnosis and treatment of IDs. This research may provide useful references for scientific research and clinical practice in the related fields.
4.XK gene deletion leading to McLeod syndrome and high-frequency antigen antibodies: identification and transfusion strategy
Jing LI ; Kewen YAO ; Yun DU ; Haiyan HU ; Hongli ZHANG
Chinese Journal of Blood Transfusion 2025;38(8):1107-1112
Objective: To investigate the hematological characteristics of the rare McLeod phenotype associated with X-linked chronic granulomatous disease, KEL and XK gene analysis, identification of unexpected antibodies, serological characteristics of high-frequency antigen antibodies, and transfusion strategies. Methods: Serological methods were employed to determine the ABO, Rh, and other blood group system antigen phenotypes of the child, along with screening and identification of unexpected antibodies. The titers of high-frequency antigen antibodies were measured using tube antihuman globulin and microcolumn gel card techniques. Kell blood group typing was performed using serological and genotyping methods, while XK gene sequencing was conducted via next-generation sequencing. Peripheral blood smears from the child's mother were examined for erythrocyte morphology. Results: The child's serological results were as follows: blood group O, ccDEE, MM, Le(a-b+), JK(a+b+), Fy(a+b-), and Kell phenotype K-k+, Kp(a-b+). Plasma analysis revealed alloantibodies anti-C、e, as well as a high-frequency antigen antibody anti-KL, with titers of 512 (tube method) and 2 048 (microcolumn gel method). Genotyping results showed KEL genotype K-k+, Kp(a-b+), Js(a-b+), while XK gene NGS identified a hemizygous deletion of exons 1-3 (XK
N. 01), consistent with XK: -1 or Kx-(McLeod). The mother's peripheral blood smear exhibited prominent acanthocytes. Conclusion: The hematological features of this rare McLeod phenotype with X-CGD include weakened Kell antigen expression and a complete exon deletion in the XK gene. Early clinical attention should be given to the symptoms and laboratory diagnosis of X-linked chronic granulomatous disease in pediatric patients. XK genotyping for McLeod phenotype should be prioritized to guide cautious transfusion strategies, preventing life-threatening complications due to incompatible blood products.
5.Effect of smoking on adjuvant chemotherapy with GC regimen for upper urinary tract urothelial carcinoma
Weisi XING ; Ruizhao HUANG ; Zhiqiang WANG ; Yun WANG ; Jing XIAO
International Journal of Surgery 2024;51(10):660-665
Objective:To study the correlation between smoking and clinicopathology in patients with upper tract urothelial carcinoma(UTUC), and to evaluate the effect of smoking on the prognosis of patients with UTUC treated with adjuvant chemotherapy for Gemcitabine plus Cisplatin (GC).Methods:A retrospective cohort study was used to select 91 patients who underwent resection of the kidney and ureter, and sleeve cystectomy in Beijing Friendship Hospital, Capital Medical University from January 2013 to December 2021, all patient received GC adjuvant chemotherapy after surgery. Patients were divided into smoking group ( n=33) and non-smoking group ( n=58) according to their smoking history. The median follow-up time was 38 months (3-83 months). The age, gender, presence or absence of hydronephrosis, tumor stage, multifocality, lymphatic vascular invasion, lymphatic metastasis, tumor grade, overall survival (OS) and cancer-specific survival (CSS) were statistically analyzed. The measurement data were expressed as mean ± standard deviation ( ± s), and the t-test was used for comparison between groups; the count data were expressed as the number of cases and percentage, and the Chi-square test was used for comparison between groups. Kaplan-Meier curve was used for survival analysis and comparison, and Long-rank test was used for comparison between groups. Cox proportional risk regression model was introduced to explore the independent influencing factors of OS and CSS by univariate and multivariate Cox regression analysis. Results:Among 91 patients, 41 were males and 50 were females, with a median age of 65 years, and 19 patients (20.9%) died, of which 17 patients (18.7%) died of UTUC. The comparison of clinical indicators between the two groups showed that smoking was associated with male, tumor stage, multifocality, lymphatic vascular invasion, lymphaitc metastasis, and tumor grade and hydronephrosis ( P<0.05). Multivariate Cox regression analysis showed that smoking, male, higher tumor stage, and lymphatic vascular invasion were independent risk factors for OS and CSS. For the subgroup of patients who smoked, smoking duration significantly affected CSS, with each additional year of smoking duration increasing the risk of death by 0.065. Conclusion:Smoking is associated with adverse pathology in patients with UTUC, and smoking is an independent factor affecting the prognosis of postoperative adjuvant chemotherapy with GC in UTUC.
6.Effects of Radix Angelica sinensis and Radix Hedysari ultrafiltration on oxidative stress and inflammatory damage of HUVECs induced by ionizing radiation and its mechanism
Li-Rong WANG ; Ling-Yun WANG ; Xiao-Jing LI ; Hui-Lin ZHAO ; Yao-Hui HUO ; Hui CHAI ; Kai LIU
Chinese Pharmacological Bulletin 2024;40(8):1501-1509
Aim To investigate the effects of Radix Angelica Sinensis and Radix Hedysari ultrafiltration(RAS-RH)on oxidative stress and inflammatory injury of human umbilical vein endothelial cells(HUVECs)induced by ionizing radiation.Methods The model of HUVECs damage induced by 6 Gy X-rays was estab-lished.HUVECs were treated with different concentra-tions of RAS-RH(100,200,400 μg·L-1).The proliferative activity of HUVECs was detected by CCK-8 method,the structural changes of mitochondria were observed by transmission electron microscope,the level of ROS was detected by DCFH-DA probe,the change of intracellular mitochondrial membrane potential was detected by JC-1 kit,and the apoptosis and cycle were detected by flow cytometry.The contents of IL-6 and TNF-α in cells were detected by ELISA.The activities of MDA,CAT,SOD and GSH-PX were detected by biochemical kit.The gene expression levels of Nrf2,HO-1,NF-κB,eNOS and IL-6 were detected by qRT-PCR,and the expression levels of Nrf2,HO-1,eNOS,NF-κB,p-NF-κB and IL-6 protein were detected by Western blot.Results Compared with the model group,RAS-RH could increase the activity of HUVECs induced by ionizing radiation,decrease the rate of ap-optosis,decrease the level of intracellular ROS,re-duce the injury of intracellular mitochondria,increase the level of mitochondrial membrane potential,promote the expression of Nrf2,HO-1 and eNOS,and inhibit the expression of NF-κB and IL-6.Conclusions RAS-RH has anti-radiation,antioxidant and anti-in-flammatory effects,which may reduce the oxidative stress and inflammatory damage of HUVECs induced by ionizing radiation by activating the activity of Nrf2/HO-1 signal pathway,thus promoting the activity of cell proliferation.
7.Research progress on mechanism of interaction between traditional Chinese medicine and intestinal flora
Jing WU ; Wei-Yi TIAN ; Kun CAI ; Su-Fang ZHOU ; Yao-Feng LI ; Xiang-Yun CHEN ; Hai-Bing QIAN ; Sha-Sha YANG
Chinese Pharmacological Bulletin 2024;40(10):1823-1829
Modern Chinese medicine studies have confirmed that the interaction between traditional Chinese medicine(TCM)and intestinal flora is the key to the treatment of diseases with tradi-tional Chinese medicine.This interplay includes such activities as:traditional Chinese medicine can be metabolized by intestinal flora into effective components with different biological activities from its precursors;TCM chemicals improve the composition of gut microbiota,consequently ameliorating its dysfunction as well as associated pathological conditions;and gut microbiota mediate the interactions between the multiple chemicals in TCM.There-fore,it becomes an important way to understand the modern sci-entific connotation of traditional Chinese medicine theory to study the pharmacological mechanism of the efficacy of traditional Chi-nese medicine by targeting Gut microbiota.
8.Effects of alone and co-administration of berberine and 5'-N-ethylformamidoadenosine on cardiomyocyte hypoxia/reoxygen injury
Mei-Na GONG ; Ya-Yun GAO ; Shu-Ying ZHANG ; Xiao-Qian PANG ; Wei TIAN ; Jing-Man XU
Chinese Pharmacological Bulletin 2024;40(12):2311-2318
Aim To investigate the effects of berberine(BBR)combined with 5'-n-ethylformamidoadenosine(NECA)on myocardial H9c2 and HL-1 cell damage induced by hypoxia/reoxygenation(H/R).Methods H9c2 and HL-1 cells were divided into the Control group,BBR group,NECA group,combined administra-tion group,H/R group,BBR+H/R group,NECA+H/R group,and combined administration+H/R group.CCK-8 was used to detect cell viability in each group.The TMRE kit was used to detect MMP.DCFH-DA was used to detect ROS content.The Mito SOX Red fluorescent probe was used to detect mitochondrial su-peroxide.The expressions of COX Ⅳ,Tom20,and Tim23 were detected by Western blot.The expression of COX Ⅳ and Tom20 genes was detected by qRT-PCR.Results In H9c2 cells,the cell viability and TMRE fluorescence intensity in the H/R group were significantly decreased compared with the Control group.The protein expressions of COX Ⅳ,Tom20,and Tim23,gene expressions of COX Ⅳ and Tom20,ROS,and mitochondrial superoxide contents were significant-ly increased.Compared with the H/R group,the cell viability of BBR and NECA were enhanced after ad-ministration alone.The contents of ROS and mitochon-drial superoxide were significantly decreased.In HL-1 cells,cell viability in the H/R group was significantly decreased compared with the Control group.The con-tents of ROS and mitochondrial superoxide were signifi-cantly increased.Compared with the H/R group,BBR and NECA alone and combined administration en-hanced cell viability.The contents of ROS and mito-chondrial superoxide were significantly decreased.Conclusion The administration of BBR and NECA a-lone or in combination can reduce the production of mi-tochondrial superoxide and cell ROS,thereby allevia-ting mitochondrial damage,alleviating oxidative stress damage,and ultimately reducing H/R-induced myocar-dial cell damage.
9.Antibiotic bone cement covered reconstruction plate for infected anterior pelvic ring fractures
Meng LI ; Ke-Jing WANG ; Zhen-Yang GAO ; Yun-Fei XIE ; Tao GUO
China Journal of Orthopaedics and Traumatology 2024;37(5):451-457
Objective To explore the clinical efficacy of antibiotic bone cement covered reconstruction steel plate in the treatment of infected anterior pelvic ring fracture.Methods From January 2017 to March 2022,11 patients with infected ante-rior pelvic ring fracture were treated with antibiotic bone cement covered reconstruction steel plate including 7 males and 4 fe-males and the age ranged from 27 to 49 years old.The pelvic fractures were classified according to the Tile typology:4 cases of Cl type,4 cases of C2 type,and 3 cases of C3 type.Among them,2 cases of infected anterior ring were infected after internal fixation of anterior ring,and 9 patients were infected with infected anterior ring due to incomplete early debridement,which was classified as infected according to the injury severity score(ISS)for 24 to 38 scores.The anterior ring was internally fixed by extended debridement,irrigation,and antibiotic bone cement covered reconstruction plate,and the posterior ring fractures were all closed reduction and internally fixed with sacroiliac screws.Results All 11 cases obtained follow-up from 13 to 20 months.A-mong them,2 patients had recurrence of postoperative infection,1 case was re-dissected and replaced with antibiotic bone cement-coated internal fixation,and 1 case had a milder infection without accumulation of the medullary cavity,and the infection was controlled by retaining the plate and replacing the antibiotic bone cement only after dissecting.Two cases developed incisional oozing,which healed after removal of the internal fixation three months postoperatively.All patients did not show pelvic fracture redisplacement or reinfection during the follow-up period.All 11 cases eventually healed bony.At the final follow-up,according to the Matta score,the fracture reduction was excellent in 6 cases,good in 4,and possible in 1.According to the Majeed functional score,it was excellent in 6,good in 3,and possible in 2.Conclusion Antibiotic bone cement covered reconstruction plate is ef-fective in the treatment of infected anterior pelvic ring fracture,with high intraoperative safety and low recurrence rate of infec-tion,which is conducive to the early postoperative rehabilitation and significantly shortens the course of the disease.
10.Visual analysis of emergency palliative care based on Web of Science database
Xuefei WU ; Shengqiang ZOU ; Yun YE ; Chunhua GE ; Jiahui LI ; Jing XIE
Chinese Journal of Modern Nursing 2024;30(7):913-919
Objective:To conduct the visual analysis of emergency palliative care based on the Web of Science database.Methods:The literature on emergency palliative care collected from 2012 to 2022 was systematically searched in the Web of Science core collection. CiteSpace software was used for visual analysis.Results:A total of 630 articles were included, and the number of publications was on the rise. The country with the highest number of publications was the United States, with 8 out of the top 10 institutions in terms of publication volume coming from the United States. The author with the highest number of publications was Grudzen. The top 10 journals in terms of citation frequency were mostly specialized journals on palliative care and first aid. The results of keyword analysis showed that a total of 15 clustering labels and 20 emergent words were output, reflecting the changes of key research objects, main research types and areas of concern.Conclusions:At present, nursing research in this field is in the development stage in China. We can draw on the practical experience of foreign countries to further explore the emergency palliative care model and service system based on China's national conditions.

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