1.Exploring Mechanism of Xiaoqinglongtang Against High Altitude Pulmonary Edema Based on Integrative Pharmacology Model
Rongrong WANG ; Chuchu WANG ; Qi XU ; Qin JIAN ; Junzhi LIN ; Ruli LI ; Chuan ZHENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):137-148
ObjectiveTo explore the potential mechanism of Xiaoqinglongtang(XQL) in the prevention and treatment of high altitude pulmonary edema(HAPE) by network pharmacology, molecular docking, and molecular dynamics simulation, and to verify it by in vivo animal model. MethodsIn this study, the active ingredients, drug targets, and HAPE-related targets of XQL were collected from BATMAN-TCM, GeneCards, and Online Mendelian Inheritance in Man(OMIM) databases. The protein-protein interaction(PPI) network was constructed by using intersection targets, and the core targets were screened and visualized by Cytoscape software. Functional annotation and pathway analysis of the intersection targets were performed by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) functional enrichment. AutoDock and GROMACS were used to evaluate the binding ability of active ingredients to key targets. In the experimental verification part, a mouse model of HAPE induced by hypobaric hypoxia(simulated 6 000 m altitude for 48 h) was established. The control effect was evaluated by hematoxylin-eosin(HE) staining, lung tissue water content, lung tissue wet/dry weight ratio, real-time quantitative polymerase chain reaction(Real-time PCR) detection of gene expression levels, and immunohistochemistry and Western blot detection of key protein expression. ResultsA total of 355 active ingredients of XQL, 2 142 targets, 716 HAPE-related targets, and 236 intersection targets were obtained by network pharmacology analysis. Key core targets such as interleukin (IL)-6, tumor necrosis factor (TNF), protein kinase B1 (Akt1), and hypoxia-inducible factor-1α (HIF-1α) were screened. The results of GO analysis of common targets involved 738 biological processes(BP), 72 cellular components(CC), and 135 molecular functions(MF). KEGG analysis effectively enriched two important signaling pathways: Phosphoinositol 3-kinase (PI3K)/Akt and HIF-1α. The results of molecular docking and molecular dynamics simulation showed that the screened active ingredients had good binding ability with key targets. In the HAPE model induced by hypobaric hypoxia(6 000 m, 48 h), the lung tissue water content, lung tissue wet/dry weight ratio, and pathological injury score of the model group were significantly increased(P<0.01), accompanied by exudation of a large number of red blood cells in the alveoli and alveolar interstitium, a significant increase in inflammatory cells, a significant widening of the alveolar septum, and mutual fusion between the alveoli. The XQL administration group significantly improved the above pathological changes(P<0.01). The results of inflammatory factor expression showed that compared with the control group, the model group showed significantly up-regulated expression of TNF-α, IL-6, and IL-1β in the lung tissue(P<0.01). Compared with the model group, the XQL administration group had significantly decreased expression of inflammatory factors(P<0.05, P<0.01). The mRNA expression of key pathway related genes PI3K, Akt1, mammalian target of rapamycin(mTOR), and HIF-1α was significantly increased in the model group(P<0.01), and decreased in a concentration-dependent manner after XQL administration(P<0.05, P<0.01). The expression levels of key proteins PI3K, phosphorylation(p)-PI3K, Akt1, p-Akt1, mTOR, p-mTOR, and HIF-1α in lung tissue were analyzed by immunohistochemistry and Western blot. Compared with the blank group, the model group showed increased expression of key proteins(P<0.05, P<0.01). Compared with the model group, the XQL administration group exhibited decreased expression of key proteins(P<0.05, P<0.01). ConclusionXQL can reduce lung inflammation and improve HAPE. The mechanism may be related to the regulation of PI3K/Akt/mTOR and HIF-1α pathways. This study provides a new idea and a theoretical basis for the treatment of HAPE with XQL.
2.Exploring Mechanism of Xiaoqinglongtang Against High Altitude Pulmonary Edema Based on Integrative Pharmacology Model
Rongrong WANG ; Chuchu WANG ; Qi XU ; Qin JIAN ; Junzhi LIN ; Ruli LI ; Chuan ZHENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):137-148
ObjectiveTo explore the potential mechanism of Xiaoqinglongtang(XQL) in the prevention and treatment of high altitude pulmonary edema(HAPE) by network pharmacology, molecular docking, and molecular dynamics simulation, and to verify it by in vivo animal model. MethodsIn this study, the active ingredients, drug targets, and HAPE-related targets of XQL were collected from BATMAN-TCM, GeneCards, and Online Mendelian Inheritance in Man(OMIM) databases. The protein-protein interaction(PPI) network was constructed by using intersection targets, and the core targets were screened and visualized by Cytoscape software. Functional annotation and pathway analysis of the intersection targets were performed by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) functional enrichment. AutoDock and GROMACS were used to evaluate the binding ability of active ingredients to key targets. In the experimental verification part, a mouse model of HAPE induced by hypobaric hypoxia(simulated 6 000 m altitude for 48 h) was established. The control effect was evaluated by hematoxylin-eosin(HE) staining, lung tissue water content, lung tissue wet/dry weight ratio, real-time quantitative polymerase chain reaction(Real-time PCR) detection of gene expression levels, and immunohistochemistry and Western blot detection of key protein expression. ResultsA total of 355 active ingredients of XQL, 2 142 targets, 716 HAPE-related targets, and 236 intersection targets were obtained by network pharmacology analysis. Key core targets such as interleukin (IL)-6, tumor necrosis factor (TNF), protein kinase B1 (Akt1), and hypoxia-inducible factor-1α (HIF-1α) were screened. The results of GO analysis of common targets involved 738 biological processes(BP), 72 cellular components(CC), and 135 molecular functions(MF). KEGG analysis effectively enriched two important signaling pathways: Phosphoinositol 3-kinase (PI3K)/Akt and HIF-1α. The results of molecular docking and molecular dynamics simulation showed that the screened active ingredients had good binding ability with key targets. In the HAPE model induced by hypobaric hypoxia(6 000 m, 48 h), the lung tissue water content, lung tissue wet/dry weight ratio, and pathological injury score of the model group were significantly increased(P<0.01), accompanied by exudation of a large number of red blood cells in the alveoli and alveolar interstitium, a significant increase in inflammatory cells, a significant widening of the alveolar septum, and mutual fusion between the alveoli. The XQL administration group significantly improved the above pathological changes(P<0.01). The results of inflammatory factor expression showed that compared with the control group, the model group showed significantly up-regulated expression of TNF-α, IL-6, and IL-1β in the lung tissue(P<0.01). Compared with the model group, the XQL administration group had significantly decreased expression of inflammatory factors(P<0.05, P<0.01). The mRNA expression of key pathway related genes PI3K, Akt1, mammalian target of rapamycin(mTOR), and HIF-1α was significantly increased in the model group(P<0.01), and decreased in a concentration-dependent manner after XQL administration(P<0.05, P<0.01). The expression levels of key proteins PI3K, phosphorylation(p)-PI3K, Akt1, p-Akt1, mTOR, p-mTOR, and HIF-1α in lung tissue were analyzed by immunohistochemistry and Western blot. Compared with the blank group, the model group showed increased expression of key proteins(P<0.05, P<0.01). Compared with the model group, the XQL administration group exhibited decreased expression of key proteins(P<0.05, P<0.01). ConclusionXQL can reduce lung inflammation and improve HAPE. The mechanism may be related to the regulation of PI3K/Akt/mTOR and HIF-1α pathways. This study provides a new idea and a theoretical basis for the treatment of HAPE with XQL.
3.Comparison of the clinical efficacy of super pulse thulium laser enucleation of the prostate with "open tunnel" and holmium laser enucleation of the prostate for benign prostatic hyperplasia
Jidong XU ; Ning JIANG ; Jian LI ; Zhikang CAI ; Jianwei LYU ; Chuanyi HU ; Jingcun ZHENG ; Zhonglin CAI ; Huiying CHEN ; Yan GU ; Yuning WANG ; Jiasheng YAN ; Zhong WANG
Journal of Modern Urology 2025;30(1):34-38
[Objective] To compare the clinical efficacy of super pulse thulium laser enucleation of the prostate (SPThuLEP) with "open tunnel" and transurethral holmium laser enucleation of the prostate (HoLEP) in the treatment of benign prostatic hyperplasia (BPH), in order to provide reference for the treatment options of BPH. [Methods] The clinical data of 112 BPH patients treated in our hospital during Jan.2023 and Jul.2023 were retrospectively analyzed, including 65 treated with SPThuLEP with "open tunnel" and 57 with HoLEP.The operation time, postoperative hemoglobin decrease, postoperative bladder irrigation, catheter indwelling time, hospitalization time and complications were compared between the two groups.The changes of maximum urine flow rate (Qmax), international prostate symptom score (IPSS), quality of life score (QoL), postvoid residual (PVR) and prostate-specific antigen (PSA) were compared between the two groups before operation and one month after operation. [Results] All operations were successful without conversion to open or transurethral plasmakinetic resection.The postoperative decrease of hemoglobin in SPThuLEP group was lower than that in HoLEP group [(13.12±6.72) g/L vs. (21.02±6.51) g/L], with statistical difference (P<0.05). There were no significant differences in the operation time [(63.35±15.73) min vs.(61.02±17.55) min], postoperative bladder irrigation time [(1.07±0.45) d vs. (1.06±0.36) d], catheter indwelling time [(2.98±0.56) d vs. (3.01±0.63) d] and hospitalization time [(3.63±0.61) d vs.(3.79±0.76) d] between the two groups (P>0.05). No blood transfusion, secondary bleeding or unplanned hospitalization occurred, and there were no serious complications such as transurethral electroresection syndrome (TURS), urethral stricture and urinary incontinence.One month after operation, the Qmax, IPSS, QoL, PVR and PSA of the two groups were significantly improved compared with those before operation (P<0.05), but with no statistical difference between the two groups (P>0.05). [Conclusion] SPThuLEP with "open tunnel" has comparable efficacy as HoLEP in the treatment of BPH.With advantages of small amount of bleeding and high safety, this minimally invasive technique can be widely popularized in clinical practice.
4.Factors influencing repeat blood donor lapsing in Guangzhou: based on the zero-inflated poisson regression model
Rongrong KE ; Guiyun XIE ; Xiaoxiao ZHENG ; Yingying XU ; Xiaochun HONG ; Shijie LI ; Yongshi DENG ; Jinyu SHEN ; Jinyan CHEN ; Jian OUYANG
Chinese Journal of Blood Transfusion 2025;38(1):73-78
[Objective] To analyze the influencing factors of repeat blood donor lapsing using a zero-inflated poisson regression model (ZIP). [Methods] The blood donation behavior of 12 498 whole blood donors from 2020 was tracked until December 31, 2023. The factors influencing the frequency of blood donations in a given year was analyzed using ZIP, and donors with 0 blood donation in that year were considered to have lapsed. The changes in relevant influencing factors associated with each blood donation were measured and modeled for analysis. [Results] The zero-inflated part of ZIP showed that the risk of lapsing of male blood donors was 2.24 times that of female blood donors (OR 95% CI:1.864-2.696, P<0.001); the risk of lapsing of the 35-44 age group and over 45 age group was respectively 40% (OR 95% CI:0.455-0.790, P<0.001) and 61%(OR 95% CI:0.268-0.578, P<0.001) lower than that of the under 25 age group; the risk of lapsing for those who have donated blood twice and ≥3 times was respectively 50% (OR 95% CI:0.405-0.609, P<0.001) and 81% (OR 95% CI:0.154-0.225, P<0.001) lower than that of first-time donors; the risk of lapsing of those with junior high or high school education was 1.2 times that of those with a college degree or higher (OR 95% CI:1.033-1.384, P<0.05); the risk of lapsing for the divorced group was 2.02 times that of the married group (OR 95% CI:1.445-2.820, P<0.001); the risk of lapsing for those with an income (Yuan) of 10 000 to 50 000, 50 000 to 100 000 and more than 100 000 was respectively 0.67 (OR 95% CI:0.552-0.818, P<0.001), 0.72 (OR 95% CI:0.591-0.884, P=0.002) and 0.67 (OR 95% CI:0.535-0.834, P<0.001) times that of those with an income (Yuan) of less than 10 000. The results of the Poisson part are consistent with the results of the zero-inflated part in terms of age and education level. [Conclusion] Blood donor lapsing is overall related to factors such as gender, age, donation frequency, education, marital status and family income. It's essential to care for those blood donors prone to lapse to retain more regular blood donors.
5.Distribution characteristics of bacterial communities in central air-conditioning ventilation systems of a Grade 3A hospital in Shanghai based on 16S rRNA sequencing
Jun NI ; Haiyun ZHANG ; Jian CHEN ; Lijun ZHANG ; Yongping LIU ; Xiaojing LI ; Yiming ZHENG ; Liping ZHANG
Journal of Environmental and Occupational Medicine 2025;42(6):732-739
Background A diverse cohort of patients and susceptible individuals congregate in healthcare facilities, where exposure to pathogenic microorganisms associated with respiratory infectious diseases constitutes a significant risk factor for cross-infection. Central air-conditioning ventilation systems improve some indoor environment indicators while exacerbating the risk of transmission of respiratory infectious diseases. Objective To investigate the distribution characteristics of microbial communities in the central air-conditioning ventilation systems of hospitals, providing a scientific basis for the selection of microbial indicators in hygiene standards for hospital central air-conditioning ventilation systems and for hospital risk early warning systems. Methods In October 2023, two central air-conditioning ventilation systems were selected from a Grade 3A hospital in Shanghai: one was an all-air air-conditioning system serving the waiting area on the ground floor, and the other was a fan coil plus fresh air system serving the outpatient area on the third floor. Samples from four different components of the ventilation systems—air outlets, filters, surface coolers, and condensate trays—were collected for high-throughput sequencing of the 16S rRNA gene to analyze bacterial communities. Alpha-diversity and beta-diversity analyses were performed to investigate the microbial community composition and diversity characteristics of the hospital central air-conditioning ventilation systems. Functional analysis was conducted to determine the relative abundance of bacterial functions in these systems.Results A total of 528 operational taxonomic units (OTUs) were identified, encompassing 20 bacterial phyla, 37 classes, 79 orders, 123 families, and 240 genera. The analysis revealed that the bacterial community was predominantly composed of Proteobacteria, Gemmatimonadates, Bacteroidetes, and Actinobacteria. The diversity analysis indicated that bacterial community richness and diversity were highest in the condensate trays, while no statistically significant differences (P > 0.05) were observed in the bacterial community composition among the air outlets, filters, and surface coolers. The functional analysis showed that the bacterial communities in the central air-conditioning ventilation systems primarily exhibited chemoheterotrophic, oxidative energy-dependent heterotrophic, and ureolytic functional characteristics. Conclusion The dominance of Proteobacteria suggests that this phylum exhibits strong adaptability in the central air-conditioning ventilation systems, possibly related to its ability to survive and reproduce under varying environmental conditions. The diversity analysis indicates that the condensate tray is a critical area for bacterial proliferation in the central air-conditioning ventilation systems. The similarity in environmental conditions among the air outlets, filters, and surface coolers result in similar bacterial community structures. The functional analysis reveals that the bacterial communities possess robust energy conversion and metabolic capabilities, potentially contributing to processes such as organic matter decomposition and nitrogen cycling within the central air-conditioning ventilation systems.
6.Plasma miRNA testing in the differential diagnosis of very early-stage hepatocellular carcinoma: a multicenter real-world study
Jie HU ; Ying XU ; Ao HUANG ; Lei YU ; Zheng WANG ; Xiaoying WANG ; Xinrong YANG ; Zhenbin DING ; Qinghai YE ; Yinghong SHI ; Shuangjian QIU ; Huichuan SUN ; Qiang GAO ; Jia FAN ; Jian ZHOU
Chinese Journal of Clinical Medicine 2025;32(3):350-354
Objective To explore the application of plasma 7 microRNA (miR7) testing in the differential diagnosis of very early-stage hepatocellular carcinoma (HCC). Methods This study is a multicenter real-world study. Patients with single hepatic lesion (maximum diameter≤2 cm) who underwent plasma miR7 testing at Zhongshan Hospital, Fudan University, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Anhui Provincial Hospital, and Peking University People’s Hospital between January 2019 and December 2024 were retrospectively enrolled. Patients were divided into very early-stage HCC group and non-HCC group, and the clinical pathological characteristics of the two groups were compared. The value of plasma miR7 levels, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) in the differential diagnosis of very early-stage HCC was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). In patients with both negative AFP and DCP (AFP<20 ng/mL, DCP<40 mAU/mL), the diagnostic value of plasma miR7 for very early-stage HCC was analyzed. Results A total of 64 528 patients from 4 hospitals underwent miR7 testing, and 1 682 were finally included, of which 1 073 were diagnosed with very early-stage HCC and 609 were diagnosed with non-HCC. The positive rate of miR7 in HCC patients was significantly higher than that in non-HCC patients (67.9% vs 24.3%, P<0.001). ROC curves showed that the AUCs for miR7, AFP, and DCP in distinguishing HCC patients from the non-HCC individuals were 0.718, 0.682, and 0.642, respectively. The sensitivities were 67.85%, 43.71%, and 44.45%, and the specificities were 75.70%, 92.78%, and 83.91%, respectively. The pairwise comparison of AUCs showed that the diagnostic efficacy of plasma miR7 detection was significantly better than that of AFP or DCP (P<0.05). Although its specificity was slightly lower than AFP and DCP, the sensitivity was significantly higher. Among patients negative for both AFP and DCP, miR7 maintained an AUC of 0.728 for diagnosing very early-stage HCC, with 67.82% sensitivity and 77.73% specificity. Conclusions Plasma miR7 testing is a potential molecular marker with high sensitivity and specificity for the differential diagnosis of small hepatic nodules. In patients with very early-stage HCC lacking effective molecular markers (negative for both AFP and DCP), miR7 can serve as a novel and effective molecular marker to assist diagnosis.
7.Seroprevalence and influencing factors of low-level neutralizing antibodies against SARS-CoV-2 in community residents
Shiying YUAN ; Jingyi ZHANG ; Huanyu WU ; Weibing WANG ; Genming ZHAO ; Xiao YU ; Xiaoying MA ; Min CHEN ; Xiaodong SUN ; Zhuoying HUANG ; Zhonghui MA ; Yaxu ZHENG ; Jian CHEN
Shanghai Journal of Preventive Medicine 2025;37(5):403-409
ObjectiveTo understand the seropositivity of neutralizing antibodies (NAb) and low-level NAb against SARS-CoV-2 infection in the community residents, and to explore the impact of COVID-19 vaccination and SARS-CoV-2 infection on the levels of NAb in human serum. MethodsOn the ground of surveillance cohort for acute infectious diseases in community populations in Shanghai, a proportional stratified sampling method was used to enroll the subjects at a 20% proportion for each age group (0‒14, 15‒24, 25‒59, and ≥60 years old). Blood samples collection and serum SARS-CoV-2 NAb concentration testing were conducted from March to April 2023. Low-level NAb were defined as below the 25th percentile of NAb. ResultsA total of 2 230 participants were included, the positive rate of NAb was 97.58%, and the proportion of low-level NAb was 25.02% (558/2 230). Multivariate logistic regression analysis indicated that age, infection history and vaccination status were correlated with low-level NAb (all P<0.05). Individuals aged 60 years and above had the highest risk of low-level NAb. There was a statistically significant interaction between booster vaccination and one single infection (aOR=0.38, 95%CI: 0.19‒0.77). Compared to individuals without vaccination, among individuals infected with SARS-CoV-2 once, both primary immunization (aOR=0.23, 95%CI: 0.16‒0.35) and booster immunization (aOR=0.12, 95%CI: 0.08‒0.17) significantly reduced the risk of low-level NAb; among individuals without infections, only booster immunization (aOR=0.28, 95%CI: 0.14‒0.52) showed a negative correlation with the risk of low-level NAb. ConclusionsThe population aged 60 and above had the highest risk of low-level NAb. Regardless of infection history, a booster immunization could reduce the risk of low-level NAb. It is recommended that eligible individuals , especially the elderly, should get vaccinated in a timely manner to exert the protective role of NAb.
8.Mechanism of Syngnathus extract in treating knee osteoarthritis of rats via regulating PI3K/Akt/mTOR signaling pathway.
Quan-Wei ZHENG ; Guo-Wei WANG ; Si-Xian WU ; Tao ZHUO ; Yi HE ; Jian-Hang LIU
China Journal of Chinese Materia Medica 2025;50(9):2442-2449
To investigate the mechanism of action of Syngnathus extract in treating knee osteoarthritis of rats, forty-eight male SD rats were randomly divided into the blank group, model group, positive drug group, as well as low-dose, medium-dose, and high-dose groups of Syngnathus extract. The rat model of knee osteoarthritis was constructed by intra-articular injection of sodium iodoacetate. After successful modeling, celecoxib(18 mg·kg~(-1)·d~(-1)) and Syngnathus extract(0.4, 0.8, and 1.6 g·kg~(-1)·d~(-1)) were given in different groups by gavage intervention for two weeks. Hematoxylin-eosin(HE) staining was used to observe the histopathological changes of cartilage in knee joints, and enzyme-linked immunosorbent assay(ELISA) was used to detect the expression level of inflammatory factors in serum. Real-time fluorescence quantitative PCR, Western blot, and immunohistochemistry were used to detect the levels of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target protein of rapamycin(mTOR) pathway-related mRNA and protein expression. The results showed that, comparied with the blank group, the cartilage surface of the knee joints of rats in the model group was uneven, with disorganized levels and defective cartilage tissue. The serum levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) and the mRNA levels of PI3K, Akt, and mTOR in cartilage tissue, as well as the protein expression levels of phosphorylated PI3K(p-PI3K)/PI3K, phosphorylated Akt(p-Akt)/Akt, phosphorylated mTOR(p-mTOR)/mTOR, and P62 were significantly increased. Beclin1 protein expression was decreased. Comparied with the model group, the number of chondrocytes in the knee joint of rats in each group of Syngnathus extract increased, and the arrangement of chondrocytes was relatively neat. The cartilage layer was restored, and the serum levels of IL-1β, IL-6, and TNF-α, as well as the mRNA expression levels of PI3K, Akt, and mTOR in cartilage tissue were significantly reduced. The protein expression levels of p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR, and P62 were significantly reduced in the rats in the middle-dose and high-dose groups of Syngnathus extract, and the Beclin1 protein expression was significantly increased. The protein expression levels of p-PI3K/PI3K, p-Akt/Akt, and P62 in rats in the low-dose group of Syngnathus extract were significantly reduced. In summary, Syngnathus extract may be used to treat knee osteoarthritis by inhibiting the expression of PI3K/Akt/mTOR signaling pathway, so as to alleviate the inflammatory response in the organism, enhance the autophagy activity of chondrocytes, and reduce the apoptosis of chondrocytes.
Animals
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TOR Serine-Threonine Kinases/genetics*
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Male
;
Rats, Sprague-Dawley
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Signal Transduction/drug effects*
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Proto-Oncogene Proteins c-akt/genetics*
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Rats
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Osteoarthritis, Knee/metabolism*
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Drugs, Chinese Herbal/administration & dosage*
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Phosphatidylinositol 3-Kinases/genetics*
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Humans
9.Integrated multiomics reveal mechanism of Aidi Injection in attenuating doxorubicin-induced cardiotoxicity.
Yan-Li WANG ; Yu-Jie TU ; Jian-Hua ZHU ; Lin ZHENG ; Yong HUANG ; Jia SUN ; Yong-Jun LI ; Jie PAN ; Chun-Hua LIU ; Yuan LU
China Journal of Chinese Materia Medica 2025;50(8):2245-2259
The combination of Aidi Injection(ADI) and doxorubicin(DOX) is a common strategy in the treatment of cancer, which can achieve synergistic anti-tumor effects while attenuating the cardiotoxicity caused by DOX. This study aims to investigate the mechanism of ADI in attenuating DOX-induced cardiotoxicity by multi-omics. DOX was used to induce cardiotoxicity in mice, and the cardioprotective effects of ADI were evaluated based on biochemical indicators and pathological changes. Based on the results, transcriptomics, proteomics, and metabolomics were employed to analyze the changes of endogenous substances in different physiological states. Furthermore, data from multiple omics were integrated to screen key regulatory pathways by which ADI attenuated DOX-induced cardiotoxicity, and important target proteins were selected for measurement by ELISA kits and immunohistochemical analysis. The results showed that ADI significantly reduced the levels of cardiac troponin T(cTnT) and N-terminal pro-B-type natriuretic peptide(NT-proBNP) and effectively ameliorated myocardial fibrosis and intracellular vacuolization, indicating that ADI showed therapeutic effect on DOX-induced cardiotoxicity. The transcriptomics analysis screened out a total of 400 differentially expressed genes(DEGs), which were mainly enriched in inflammatory response, oxidative stress, and myocardial fibrosis. After proteomics analysis, 70 differentially expressed proteins were selected, which were mainly enriched in the inflammatory response, cardiac function, and energy metabolism. A total of 51 differentially expressed metabolites were screened by the metabolomics analysis, and they were mainly enriched in multiple signaling pathways, including the inflammatory response, lipid metabolism, and energy metabolism. The integrated data of multiple omics showed that linoleic acid metabolism, arachidonic acid metabolism, and glycerophosphate metabolism pathways played an important role in DOX-induced cardiotoxicity, and ADI may exert therapeutic effects by modulating these pathways. Target validation experiments suggested that ADI significantly regulated abnormal protein levels of cyclooxygenase-1(COX-1), cyclooxygenase-2(COX-2), prostaglandin H2(PGH2), and prostaglandin D2(PGD2) in the model group. In conclusion, ADI may attenuate DOX-induced cardiotoxicity by regulating linoleic acid metabolism, arachidonic acid metabolism, and glycerophosphate metabolism, thus alleviating inflammation of the body.
Doxorubicin/toxicity*
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Animals
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Mice
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Cardiotoxicity/genetics*
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Drugs, Chinese Herbal/administration & dosage*
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Male
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Proteomics
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Metabolomics
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Injections
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Humans
;
Multiomics
10.Mechanism of Hippocampus in treatment of knee osteoarthritis based on network pharmacology, molecular docking, and experimental verification.
Tao ZHUO ; Guo-Wei WANG ; Si-Xian WU ; Quan-Wei ZHENG ; Yi HE ; Jian-Hang LIU
China Journal of Chinese Materia Medica 2025;50(14):4026-4036
This study predicts the potential mechanism of Hippocampus in the treatment of knee osteoarthritis(KOA) through network pharmacology, with preliminary verification using molecular docking and animal experiments. The database was used to screen the active chemical components of Hippocampus and the targets of KOA, and Gene Ontology(GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis, and molecular docking were performed on the relevant core targets to preliminarily explore the potential targets and mechanisms of Hippocampus in the treatment of KOA. A rat KOA model was constructed by intra-articular injection of sodium iodoacetate, and the rats were intervened with different doses of Hippocampus decoction and celecoxib. The expression of relevant targets was detected through hematoxylin-eosin(HE) staining, enzyme-linked immunosorbent assay(ELISA), RT-qPCR, and Western blot to further validate the network pharmacology results. A total of 23 drug-like components of the Hippocampus were screened, and 128 common targets with KOA were identified, involving interleukin-17(IL-17) signaling pathway, transcription factor(FoxO) signaling pathway, tumor necrosis factor(TNF) signaling pathway. Molecular docking results showed that the screened core chemical components exhibited good affinity with key targets. HE staining demonstrated that Hippocampus improved the morphology of the cartilage layer. ELISA confirmed that Hippocampus significantly reduced the levels of IL-6 and TNF-α in the serum of KOA rats. Western blot and RT-qPCR analysis showed that Hippocampus significantly reduced the expression of IL-6, TNF-α, matrix metalloproteinase(MMP) 13, IL-17A, nuclear factor κB activator 1(ACT1), tumor necrosis factor receptor-associated factor 6(TRAF6) and nuclear factor κB(NF-κB) in cartilage tissue. The results suggest that Hippocampus can alleviate the degree of joint damage in the KOA rat model induced by sodium iodoacetate. The mechanism of action is related to the inhibition of the IL-17 signaling pathway, reduction of inflammation, and inhibition of extracellular matrix(ECM) degradation.
Animals
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Molecular Docking Simulation
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Rats
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Drugs, Chinese Herbal/administration & dosage*
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Network Pharmacology
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Male
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Osteoarthritis, Knee/metabolism*
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Rats, Sprague-Dawley
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Signal Transduction/drug effects*
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Humans
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Interleukin-17/metabolism*
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Tumor Necrosis Factor-alpha/metabolism*
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Disease Models, Animal
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Hippocampus/chemistry*

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