1.Mechanistic investigation of FOXO4 in Celastrus orbiculatus extract-mediated inhibition of aerobic glycolysis in the therapy of gastric precancerous lesions
Ziwei PAN ; Junsong WEN ; Xuedan YAO ; Yanqing LIU ; Yaodong ZHU
Acta Universitatis Medicinalis Anhui 2026;61(3):462-469
ObjectiveTo investigate the effects of forkhead box protein O4 (FOXO4) expression on gastric precancerous lesions (GPL), and to clarify its mechanism in mediating the therapeutic effect of Celastrus orbiculatus extract (COE) on GPL by regulating aerobic glycolysis. MethodsReferring to the previously established combined modeling protocol in our research group, a rat model of gastric precancerous lesions (GPL) was constructed through the following procedures: rats were given free access to 170 μg/mL N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) solution for ad libitum drinking, fed with a diet supplemented with 0.03% ranitidine hydrochloride, and treated with a cycling regimen of “2-day feeding followed by 1-day fasting”. Specifically, on the afternoon of each fasting day, the rats received intragastric administration of 2% sodium salicylate at a dose of 10 mL/kg body weight. FOXO4-silenced and overexpression model rats were constructed by tail vein injection of plasmids. The rats were randomly divided into control, model, COE, overexpression negative control (OE-NC), FOXO4 overexpression (OE-FOXO4), OE-FOXO4+COE, silencing negative control (shNC), FOXO4 silencing (shFOXO4) and shFOXO4+COE groups. Gastric mucosal histopathological changes were observed in each group. Lactic acid content in gastric mucosal tissues was detected by colorimetry. The expression levels of FOXO4, HK2, PKM2, LDHA and GLUT1 were evaluated by immunohistochemistry (IHC), and their mRNA levels were determined by RT-PCR.Results Compared with the control group, the COE, OE-FOXO4 and OE-FOXO4+COE groups exhibited significantly improved gastric mucosal lesions, reduced lactic acid levels, weakened expression of aerobic glycolysis-related proteins (PKM2, HK2, LDHA, GLUT1), and enhanced FOXO4 expression. The OE-FOXO4+COE group showed the lowest lactic acid level and more pronounced changes in related protein expression compared with the COE and OE-FOXO4 groups. In contrast, the shFOXO4 and shFOXO4+COE groups displayed increased lactic acid levels, enhanced expression of aerobic glycolysis-related proteins, and reduced FOXO4 expression compared with the model group.ConclusionFOXO4 expression is involved in the inhibitory effect of COE on GPL, possibly by regulating the aerobic glycolysis process.
2.Application of combined respiratory training in the family-centered model in Mycoplasma-associated bronchopneumonia children
Wanli XIE ; Junsong CHEN ; Yiling PAN ; Linmei HUANG ; Yali CHU
China Modern Doctor 2025;63(23):10-13
Objective To analyze the application of combined respiratory training in Mycoplasma-associated bronchopneumonia children and its effect on pulmonary function under family-centered model.Methods A total of 150 Children with Mycoplasma-associated bronchopneumonia treated at Hangzhou Children's Hospital from April 2023 to April 2024 were selected as subjects.The children were divided into control group(n=75)and study group(n=75)using a randomized digital table method.The control group received standard interventions,while the study group received family-centered combined respiratory training in addition to control group's treatment.The two groups were compared in terms of pulmonary function,symptom improvement duration,treatment compliance,and patient satisfaction.Results After intervention,compared with the control group,children in study group had higher forced vital capacity(FVC),forced expiratory volume in one second(FEV1),FEV1/FVC levels,total treatment compliance and satisfaction,the improvement time of cough,fever and dyspnea were shorter,the difference were statistically significant(P<0.05).Conclusion The use of family-centered combined respiratory training can improve the pulmonary function of children with mycoplasma infection and bronchopneumonia,shorten the time for symptom improvement,and improve the treatment compliance and satisfaction of children.
3.Effect of Celastrus orbiculatus extract on gastric precancerous lesions through the regulation of the Notch-1 signaling pathway
Junsong Wen ; Ziwei Pan ; Yanqing Liu ; Yaodong Zhu
Acta Universitatis Medicinalis Anhui 2025;60(2):313-320
Objective :
To observe the effect of Celastrus orbiculatusextract(COE) on gastric precancerous lesions(GPL) and to explore its role in the Notch-1 signaling pathway.
Methods :
GPL rat models were established using a composite model replication method, and the rats were randomly divided into a control group, a model group, and COE low, medium and high dose groups [COE at 12.5, 25, and 50 mg/(kg·d)]. After 4 weeks of intervention, gastric tissue was collected, and immunohistochemistry(IHC) was performed to detect the expression of mucins(MUC2, MUC5AC, and MUC6), Leucine-rich repeat-containing G-protein coupled receptor 5(Lgr5), Proliferating Cell Nuclear Antigen(Ki67), and Notch-1. Polymerase chain reaction(PCR) was used to determine the mRNA levels of the aforementioned mucins. Human gastric epithelial cells(GES-1) were induced with N-Methyl-N′-nitro-N-nitrosoguanidine(MNNG) to establish a GPL cell model. The cells were randomly divided into control, model, and COE low, medium, and high concentration groups(COE at 5, 10, and 20 μg/ml). After 24 hours of corresponding interventions, changes in cell morphology were observed under an inverted microscope. Western blot was used to measure the expression of Notch-1 and Lgr5, and immunofluorescence(IF) was employed to detect Notch-1 expression.
Results :
Compared to the control group, the expression of MUC2, Lgr5, Notch-1, and Ki67 in the gastric tissue of the model group rats significantly increased(P<0.000 1), while the expression of MUC5AC and MUC6 decreased(P<0.000 1). In comparison to the model group, the expressions of MUC2, Lgr5, Notch-1, and Ki67 were significantly reduced in the COE groups(P<0.01), while the expression of MUC5AC and MUC6 significantly increased(P<0.01). In the GES-1 model group, the cells exhibited irregular morphology, loose intercellular connections, and disorganized arrangement compared to the control group. In contrast, the cells in the COE groups displayed a more regular morphology and a more organized arrangement than those in the model group. Additionally, compared to the control group, the expression of Lgr5 and Notch-1 in the model group were significantly elevated(P<0.000 1), whereas after COE treatment, their expressions were markedly reduced(P<0.001).
Conclusion
COE can alleviate GPL, and its mechanism may be associated with the downregulation of the Notch-1 signaling pathway, which improves gastric mucosal mucin barrier function and inhibits the abnormal proliferation of gastric mucosal stem cells.
4.Application of combined respiratory training in the family-centered model in Mycoplasma-associated bronchopneumonia children
Wanli XIE ; Junsong CHEN ; Yiling PAN ; Linmei HUANG ; Yali CHU
China Modern Doctor 2025;63(23):10-13
Objective To analyze the application of combined respiratory training in Mycoplasma-associated bronchopneumonia children and its effect on pulmonary function under family-centered model.Methods A total of 150 Children with Mycoplasma-associated bronchopneumonia treated at Hangzhou Children's Hospital from April 2023 to April 2024 were selected as subjects.The children were divided into control group(n=75)and study group(n=75)using a randomized digital table method.The control group received standard interventions,while the study group received family-centered combined respiratory training in addition to control group's treatment.The two groups were compared in terms of pulmonary function,symptom improvement duration,treatment compliance,and patient satisfaction.Results After intervention,compared with the control group,children in study group had higher forced vital capacity(FVC),forced expiratory volume in one second(FEV1),FEV1/FVC levels,total treatment compliance and satisfaction,the improvement time of cough,fever and dyspnea were shorter,the difference were statistically significant(P<0.05).Conclusion The use of family-centered combined respiratory training can improve the pulmonary function of children with mycoplasma infection and bronchopneumonia,shorten the time for symptom improvement,and improve the treatment compliance and satisfaction of children.
5.Mining and analysis of ADE signals of two camptothecin topoisomerase 1 inhibitors
Zhenjiang WU ; Jianjun LIU ; Xiangyu BAI ; Maofan YANG ; Wenhai FAN ; Pan WANG ; Junsong YANG
China Pharmacy 2024;35(9):1133-1138
OBJECTIVE To mine and analyze the adverse drug events (ADE) signals of two camptothecin topoisomerase 1 inhibitors, i.e. irinotecan and topotecan, and to provide reference for clinical medication safety. METHODS Based on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database, ADE report data for the aforementioned two drugs were extracted from January 1, 2004 to March 31, 2023. After processing the data, signal mining was conducted by using the reporting odds ratio in conjunction with the Bayesian confidence propagation neural network, followed by analysis. RESULTS A total of 14 738 relevant ADE reports were screened, among which 11 483 were associated with irinotecan and 3 255 with topotecan. The ADE reports for irinotecan were predominantly male, whereas for topotecan, they were predominantly female; the age of patients using the two drugs mainly concentrated in 45-<75 years old. A total of 847 signals were detected, involving 24 system organ classes (SOCs). Among them, 565 signals of irinotecan were detected, involving 24 SOCs, primarily concentrating on gastrointestinal disorders, general disorders and administration site conditions, blood and lymphatic system disorders; the most frequently reported ADE was diarrhea, and the ADE with the strongest signal intensity was cholinergic syndrome. A total of 282 signals of topotecan were detected, involving 22 SOCs, primarily concentrating on general disorders and administration site conditions, investigations, blood and lymphatic system disorders, and gastrointestinal disorders; the most frequently reported ADEs were death and anemia, and the ADE with the strongest signal intensity was febrile bone marrow aplasia. ADE signals for irinotecan such as metastatic colorectal cancer, peripheral sensory neuropathy, steatohepatitis, and those for topotecan such as iris atrophy, retinal degeneration, vitreous hemorrhage, were not documented in their respective drug instruction. CONCLUSIONS ADEs of irinotecan and topotecan primarily involve the digestive and hematologic systems, warranting close clinical monitoring. Cholinergic syndrome caused by irinotecan should be concerned. In addition, patients receiving irinotecan should also be monitored for ADE such as metastatic colorectal cancer, peripheral sensory neuropathy, steatohepatitis, and proteinuria; for patients using topotecan, enhanced surveillance of ocular diseases is recommended to ensure medication safety.
6.Analysis of catharanthine content and agronomic traits in Catharanthus roseus.
Xiaofen SUN ; Yu CHEN ; Junsong PAN ; Yuliang WANG ; Kexing SUN ; Run CAI ; Kexuan TANG
China Journal of Chinese Materia Medica 2009;34(2):128-131
Catharanthine content and agronomic traits in major Catharanthus roseus varieties were analyzed. It was found that there existed great difference in catharanthine content and agronomic traits among the varieties. Catharanthine content was the highest in variety Pacifica Polka Dot (PPD), reaching 3.79 mg g(-1) dry leaf weight, and the lowest in variety Cooler Pink (CP) with only 0.9 mg g(-1) dry leaf weight. Correlation existed in certain extent between catharanthine content and agronomic traits in C. roseus. Path analysis showed that among all the agronomic traits analyzed, internodal distance positively affected catharanthine content at significant level (P<0.05), with the path coefficient being 1.473. This study provides useful information for high-catharanthine content C. roseus introduction and breeding.
Catharanthus
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anatomy & histology
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chemistry
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metabolism
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Plant Leaves
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anatomy & histology
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chemistry
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metabolism
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Vinca Alkaloids
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analysis
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metabolism


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