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.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.
3.Preparation and performance evaluation of large diameter artificial vessels modified with polydopamine/gelatin/earthworm active protein
Xin FENG ; Xinyu PAN ; Xuewei ZHANG ; Xiao LIU ; Ziwei ZHAO ; Yicheng LI ; Tuo YANG ; Wentao LI ; Liang ZHAO ; Wenbin LI
Chinese Journal of Thoracic and Cardiovascular Surgery 2025;41(5):284-294
Objective:To investigate a novel coating technology for artificial blood vessel pipelines, conducting preliminary tests on the mechanical stability, hemocompatibility, and biocompatibility of the coating.Methods:The polyester braided artificial blood vessels produced by Terumo Corporation were subjected to three different experimental treatments and divided into three groups. Model group: The uncoated artificial blood vessels were thoroughly cleaned and freeze-dried. Experimental group: The artificial blood vessels were first immersed in a dopamine solution to form a polydopamine(PDA) coating on their surface, and then further immersed in an earthworm active protein/gelatin(EWAP/GT) solution to create PDA/GT/EWAP-modified artificial blood vessels. Collagen group: The untreated polyester woven artificial blood vessels served as the control. The study detailed the characterization, porosity, water permeability, degradation rate, blood compatibility, and cytotoxicity of the PDA/GT/EWAP-coated artificial blood vessels. Additionally, a 2-week in vivo study was conducted to evaluate the biocompatibility of the PDA/GT/EWAP-coated artificial blood vessels implanted subcutaneously in SD rats.Results:The PDA/GT/EWAP-coated artificial vascular grafts were successfully fabricated. The artificial blood vessels in the PDA/GT/EWAP group exhibited a porosityof(50.53±1.10)%, with water permeability showing a gradual decreasing trend over time. The overall in vitro degradation rate at 4 weeks was(1.83±0.08)%, and the PDA/GT/EWAP group demonstrated favorable mechanical stability. The activated partial thromboplastin time(APTT) of the PDA/GT/EWAP group was(26.30±0.46)s, the thrombin time(TT) was(18.83±0.49)s, the hemolysis rate was(2.15±0.09)%, and the plasma recalcification time(PRT) was(191.00±10.54)s, indicating excellent blood compatibility and anticoagulant properties. MTT assay evaluation of the PDA/GT/EWAP group revealed no significant cytotoxicity. After subcutaneous implantation of vascular samples in rats for 2 weeks, analysis of blood immune parameters and hematoxylin-eosin(HE) staining of the artificial vascular samples showed that the immune response in the PDA/GT/EWAP group exhibited no significant difference compared to the collagen group and was superior to the model group. Conclusion.Conclusion:The PDA/GT/EWAP composite-coated artificial blood vessel demonstrates excellent mechanical properties, good hemocompatibility, biocompatibility, and low cytotoxicity. It also shows remarkable stability. This research offers a new approach for domestic technological breakthroughs in related fields.
4.Screening and fermentation condition optimization of Streptomyces scabies antagonists.
Mengyan DOU ; Ziwei WANG ; Pan ZHAO ; Xiu WANG ; Aiping WANG ; Naiqin ZHONG
Chinese Journal of Biotechnology 2025;41(10):3747-3763
In recent years, potato scab caused by Streptomyces scabies is aggravating year by year, becoming an industrial problem urgently to be resolved. Screening antagonistic bacteria with good inhibitory effect and wide adaptability is the main measure to realize effective prevention and control of the disease. This study screened three strains of antagonistic bacteria DXT2-4, T2-1 and 21-14 with good inhibitory effect on S. scabies by using plate standoff test, and identified them as Bacillus altitudinis, Bacillus safensis and Bacillus pumilus, respectively, based on morphological characteristics, physiological and biochemical properties, and 16S rRNA gene sequences. DXT2-4, T2-1 and 21-14 showed the pot control efficacy of 68.83%, 48.57%, and 57.14%, respectively. The field control efficacy of the three strains was 59.48%, 34.58% and 51.75% in Hulun Buir, Inner Mongolia Autonomous Region and 55.14%, 36.05%, and 49.05% in Huizhou, Guangdong. The three strains could grow normally in the media with pH 1.0-13.0 and with 1%-11% NaCl, and they had inhibitory effects on Rhizoctonia solani, Verticillium dahliae, Alternaria solani, and Fusarium oxysporum. The indole-3-acetic acid yields of DXT2-4, T2-1, and 21-14 were 2.23, 1.11, and 1.67 mg/L, respectively. DXT2-4 and 21-14 demonstrated strong abilities to solubilize phosphorus. The optimal carbon source, nitrogen source, and inorganic salt for fermentation of strain DXT2-4 were 2% molasses+2% corn starch, 2% soybean meal, and 0.3% MgSO4·7H2O, respectively. These findings suggest the three strains of bacteria can efficiently inhibit the growth of S. scabies and have strong environmental adaptability. Particularly, DXT2-4 has the best effects of inhibiting the disease and promoting plant growth, showing a high development value and broad application prospects, this is of great significance for promoting sustainable potato production and ensuring the environmentally sound utilization of resources.
Streptomyces/metabolism*
;
Fermentation
;
Plant Diseases/prevention & control*
;
Solanum tuberosum/growth & development*
;
Bacillus/growth & development*
;
Antibiosis
5.ACTH-independent Cushing′s syndrome caused by a GNAS hotspot mutation: Case reports of two rare patients with McCune-Albright syndrome complicated by Cushing′s syndrome and literature review
Ziwei CHEN ; Congcong XIA ; Ning PAN ; Zhuozhou CUI ; Li JIANG ; Ni ZHEN ; Yuan XIAO ; Zhiya DONG ; Xiaoyu MA ; Wenli LU
Chinese Journal of Endocrinology and Metabolism 2025;41(6):497-504
McCune-Albright syndrome(MAS) is a postzygotic somatic mutation disorder caused by activating mutations in the GNAS gene, which encodes the α subunit of the stimulatory G protein. Its clinical features typically include polyostotic fibrous dysplasia, cafe-au-lait skin pigmentation, and endocrine hyperactivity, such as Cushing′s syndrome, hyperthyroidism, and growth hormone excess. Here, we report two rare cases of MAS complicated with adrenocorticotropic hormone(ACTH)-independent Cushing syndrome, and provide a review and analysis of previously reported MAS cases associated with Cushing′s syndrome.
6.Analysis of disease burden status and trends of hip osteoarthritis in China,1990-2021
Shengpeng ZHENG ; Zheng LI ; Weilong XU ; Jiawen PAN ; Ziwei JIANG ; Feng HUANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(2):257-264
Objective To analyze the disease burden of hip osteoarthritis(HOA)and its changing trends in China from 1990 to 2021.Methods Utilizing the Global Burden of Disease(GBD)2021 database,age-standardized incidence rate(ASIR),age-standardized prevalence rate(ASPR),and age-standardized disability adjusted life years(DALY)rate(ASDR)of HOA were compared and analyzed in China,globally,and in regions with high sociodemographic index(SDI)from 1990 to 2021.Joinpoint regression model was used to analyze the temporal trend of disease burden,and age and gender were combined to deeply analyze the disease burden of HOA in China.Meanwhile,the age-period-cohort model was used to analyze the influencing factors and the Bayesian age-period-cohort model to predict the trend of China's HOA disease burden in the next 10 years.Results The ASIR,ASPR,and ASDR of HOA in China showed an increasing trend from 1990 to 2021[average annual percentage change(AAPC)were 0.87%,0.82%,and 0.81%,respectively,P<0.001],and their AAPCs were higher than those of the global and high SDI regions,but in 2021,the ASIR,ASPR,and ASDR of China were lower than those of the global and high SDI regions.Crude incidence,crude prevalence,and crude DALY rate in Chinese HOA increased with age,with the highest number of incidence in the 55-59 age group and the highest number of prevalence,DALY,in the 65-69 age group.In 2021,the ASIR,ASPR and ASDR of HOA in Chinese males were 1.25,1.24 and 1.25 times higher than those in females.Changes in the incidence of HOA in China from 1990 to 2021 were influenced by age,period,and birth cohort.Compared with 2021,new cases of HOA are expected to increase by 37.78%by 2035,and the number of incidence cases in people aged 60 years and above will increase significantly.Conclusion The disease burden of HOA in China continued to rise from 1990 to 2021,and prevention and control need to be strengthened,with a focus on men,high BMI,and middle-aged and older populations.
7.Effects of exercise preconditioning on hippocampal microglial polarization and demyelination in rats with vascular dementia model
Pan CHEN ; Ziwei XIE ; Xin TANG
Chinese Journal of Rehabilitation Medicine 2025;40(5):652-660
Objective:To investigate the effects of exercise preconditioning on hippocampal microglia polarization and my-elin loss in vascular dementia(VD)model rats.Method:Sixty male SPF SD rats were randomly divided into sham group,model group,exercise precondition-ing sham group and exercise preconditioning model group,with 15 rats in each group.The exercise precondi-tioning rats was trained in weightless swimming exercise for 4 weeks(5sessions/week,30min/session)before mod-eling.The VD model was established by bilateral common carotid artery ligation.Behavioral tests were conduct-ed using the Morris water maze,and the demyelination in the CA1 region of the hippocampus was observed by Luxol fast blue staining.The polarization of microglia in the CA1 region of the hippocampus was observed by immunofluorescence double labeling staining,and the contents of interleukin 4(IL-4),interleukin 10(IL-10),interleukin-1 beta(IL-1β),and tumor necrosis factor-α(TNF-α)in the serum were detected by ELISA.Result:Four weeks after modeling,the average escape latency of rats in the model group was prolonged and the number of platform crossings was reduced compared with the sham group(P<0.05);the average escape laten-cy of rats in the exercise preconditioning model group was prolonged and the number of platform crossings was reduced compared with the exercise preconditioning sham group(P<0.05);the escape latency of rats in the model group was prolonged compared with the exercise preconditioning model group(P<0.05).The histological demyelination score showed that compared with the sham group,the demyelination in the model group was in-creased(P<0.05);the demyelination in the exercise preconditioning model group was increased compared with the exercise preconditioning sham group(P<0.05);the demyelination in the model group was increased compared with the exercise preconditioning model group(P<0.05).Compared with the sham group,the expression of in-ducible nitric oxide synthase(iNOS)protein in the CA1 region of the hippocampus in the model group was in-creased,while the expression of arginase1(Arg1)protein was decreased(P<0.05).Compared with the exercise preconditioning sham group,the expression of iNOS protein in the CA1 region of the hippocampus in the exer-cise preconditioning model group was significantly increased(P<0.05),while the expression of Arg-1 protein was significantly decreased(P<0.05).Compared with the exercise preconditioning model group,the expression of iN-OS protein in the CA1 region of the hippocampus in the model group was increased,while the expression of Arg1 protein was decreased(P<0.05).Compared with the sham group,the contents of IL-4 and IL-10 in the se-rum of rats in the model group decreased,while the contents of IL-1β and TNF-α increased(P<0.05).Compared with the exercise preconditioning sham group,the contents of IL-4 and IL-10 in the serum of rats in the exer-cise preconditioning model group decreased,while the contents of IL-1β and TNF-α increased(P<0.05).Com-pared with the exercise preconditioning model group,the content of IL-4 in the serum of rats in the model group decreased,while the content of IL-1β increased(P<0.05).Conclusion:Exercise preconditioning can promote microglial M2 polarization and myelin fragment phagocyto-sis,inhibit hippocampal nerve inflammation,and improve the learning and memory ability of rats with vascu-lar dementia.
8.Analysis of disease burden status and trends of hip osteoarthritis in China,1990-2021
Shengpeng ZHENG ; Zheng LI ; Weilong XU ; Jiawen PAN ; Ziwei JIANG ; Feng HUANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(2):257-264
Objective To analyze the disease burden of hip osteoarthritis(HOA)and its changing trends in China from 1990 to 2021.Methods Utilizing the Global Burden of Disease(GBD)2021 database,age-standardized incidence rate(ASIR),age-standardized prevalence rate(ASPR),and age-standardized disability adjusted life years(DALY)rate(ASDR)of HOA were compared and analyzed in China,globally,and in regions with high sociodemographic index(SDI)from 1990 to 2021.Joinpoint regression model was used to analyze the temporal trend of disease burden,and age and gender were combined to deeply analyze the disease burden of HOA in China.Meanwhile,the age-period-cohort model was used to analyze the influencing factors and the Bayesian age-period-cohort model to predict the trend of China's HOA disease burden in the next 10 years.Results The ASIR,ASPR,and ASDR of HOA in China showed an increasing trend from 1990 to 2021[average annual percentage change(AAPC)were 0.87%,0.82%,and 0.81%,respectively,P<0.001],and their AAPCs were higher than those of the global and high SDI regions,but in 2021,the ASIR,ASPR,and ASDR of China were lower than those of the global and high SDI regions.Crude incidence,crude prevalence,and crude DALY rate in Chinese HOA increased with age,with the highest number of incidence in the 55-59 age group and the highest number of prevalence,DALY,in the 65-69 age group.In 2021,the ASIR,ASPR and ASDR of HOA in Chinese males were 1.25,1.24 and 1.25 times higher than those in females.Changes in the incidence of HOA in China from 1990 to 2021 were influenced by age,period,and birth cohort.Compared with 2021,new cases of HOA are expected to increase by 37.78%by 2035,and the number of incidence cases in people aged 60 years and above will increase significantly.Conclusion The disease burden of HOA in China continued to rise from 1990 to 2021,and prevention and control need to be strengthened,with a focus on men,high BMI,and middle-aged and older populations.
9.Effects of exercise preconditioning on hippocampal microglial polarization and demyelination in rats with vascular dementia model
Pan CHEN ; Ziwei XIE ; Xin TANG
Chinese Journal of Rehabilitation Medicine 2025;40(5):652-660
Objective:To investigate the effects of exercise preconditioning on hippocampal microglia polarization and my-elin loss in vascular dementia(VD)model rats.Method:Sixty male SPF SD rats were randomly divided into sham group,model group,exercise precondition-ing sham group and exercise preconditioning model group,with 15 rats in each group.The exercise precondi-tioning rats was trained in weightless swimming exercise for 4 weeks(5sessions/week,30min/session)before mod-eling.The VD model was established by bilateral common carotid artery ligation.Behavioral tests were conduct-ed using the Morris water maze,and the demyelination in the CA1 region of the hippocampus was observed by Luxol fast blue staining.The polarization of microglia in the CA1 region of the hippocampus was observed by immunofluorescence double labeling staining,and the contents of interleukin 4(IL-4),interleukin 10(IL-10),interleukin-1 beta(IL-1β),and tumor necrosis factor-α(TNF-α)in the serum were detected by ELISA.Result:Four weeks after modeling,the average escape latency of rats in the model group was prolonged and the number of platform crossings was reduced compared with the sham group(P<0.05);the average escape laten-cy of rats in the exercise preconditioning model group was prolonged and the number of platform crossings was reduced compared with the exercise preconditioning sham group(P<0.05);the escape latency of rats in the model group was prolonged compared with the exercise preconditioning model group(P<0.05).The histological demyelination score showed that compared with the sham group,the demyelination in the model group was in-creased(P<0.05);the demyelination in the exercise preconditioning model group was increased compared with the exercise preconditioning sham group(P<0.05);the demyelination in the model group was increased compared with the exercise preconditioning model group(P<0.05).Compared with the sham group,the expression of in-ducible nitric oxide synthase(iNOS)protein in the CA1 region of the hippocampus in the model group was in-creased,while the expression of arginase1(Arg1)protein was decreased(P<0.05).Compared with the exercise preconditioning sham group,the expression of iNOS protein in the CA1 region of the hippocampus in the exer-cise preconditioning model group was significantly increased(P<0.05),while the expression of Arg-1 protein was significantly decreased(P<0.05).Compared with the exercise preconditioning model group,the expression of iN-OS protein in the CA1 region of the hippocampus in the model group was increased,while the expression of Arg1 protein was decreased(P<0.05).Compared with the sham group,the contents of IL-4 and IL-10 in the se-rum of rats in the model group decreased,while the contents of IL-1β and TNF-α increased(P<0.05).Compared with the exercise preconditioning sham group,the contents of IL-4 and IL-10 in the serum of rats in the exer-cise preconditioning model group decreased,while the contents of IL-1β and TNF-α increased(P<0.05).Com-pared with the exercise preconditioning model group,the content of IL-4 in the serum of rats in the model group decreased,while the content of IL-1β increased(P<0.05).Conclusion:Exercise preconditioning can promote microglial M2 polarization and myelin fragment phagocyto-sis,inhibit hippocampal nerve inflammation,and improve the learning and memory ability of rats with vascu-lar dementia.
10.ACTH-independent Cushing′s syndrome caused by a GNAS hotspot mutation: Case reports of two rare patients with McCune-Albright syndrome complicated by Cushing′s syndrome and literature review
Ziwei CHEN ; Congcong XIA ; Ning PAN ; Zhuozhou CUI ; Li JIANG ; Ni ZHEN ; Yuan XIAO ; Zhiya DONG ; Xiaoyu MA ; Wenli LU
Chinese Journal of Endocrinology and Metabolism 2025;41(6):497-504
McCune-Albright syndrome(MAS) is a postzygotic somatic mutation disorder caused by activating mutations in the GNAS gene, which encodes the α subunit of the stimulatory G protein. Its clinical features typically include polyostotic fibrous dysplasia, cafe-au-lait skin pigmentation, and endocrine hyperactivity, such as Cushing′s syndrome, hyperthyroidism, and growth hormone excess. Here, we report two rare cases of MAS complicated with adrenocorticotropic hormone(ACTH)-independent Cushing syndrome, and provide a review and analysis of previously reported MAS cases associated with Cushing′s syndrome.


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