1.Pharmacodynamic Effect and Mechanism of Xiaoke Drink in Ameliorating Insulin Resistance in ob/ob Mice
Baoying LI ; Baosheng ZHAO ; Yuling ZHA ; Mi DENG ; Luna NIU ; Xuefei LI ; Ruowei ZHU ; Yu DONG ; Lu JING
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):254-260
ObjectiveTo observe the effect of Xiaoke drink on insulin resistance in ob/ob mice and explore the mechanism. MethodEighteen ob/ob mice were randomly assigned into model, Xiaoke drink (17.68 g·kg-1), and atorvastatin (0.01 g·kg-1) groups (n=6), and six C57BL/6 mice were selected as the normal group. Mice in the normal and model groups were administrated with the same amount of distilled water. Fasting body weight, weekly food intake, and weekly water intake were measured at a fixed time. Fasting plasma glucose (FPG) and 2-hour post-load plasma glucose (2 hPG) were measured before and after 8-week intervention. After intervention, total cholesterol (TC), triglyceride (TG), fasting insulin (FINS), Homeostasis Model Assessment-Insulin Resistance (HOMA-IR), blood routine, and alkaline phosphatase (ALP) were measured. Western blot was employed to determine the expression levels of ubiquitin-specific protease 20 (USP20) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) in the liver. The pancreas was stained with hematoxylin-eosin for observation. ResultCompared with the model group, the Xiaoke drink group showed decreased body weight of ob/ob mice (P<0.05, P<0.01), declined growth trend of body weight (P<0.05, P<0.01), reduced weekly average water intake, lowered levels of FPG, 2 hPG, TC, and HOMA-IR (P<0.05, P<0.01), and down-regulated expression level of USP20 in the liver (P<0.05). HMGCR content was positively correlated with USP20 expression. In addition, Xiaoke drink promoted the recovery of islet tissue morphology and function in ob/ob mice. ConclusionXiaoke drink can ameliorate insulin resistance in ob/ob mice by inhibiting USP20/HMGCR expression, reversing cholesterol biosynthesis process, and reducing cholesterol level.
2.Development and performance evaluation of an antioxidant gene-knockout microbial sensor for active monitoring of DNA damage effects
Yue YU ; Anyi LI ; Wenjia WANG ; Hao JIANG ; Yulin DENG ; Xiaoqiong LI ; Xuefei LYU ; Rongji DAI
Space Medicine & Medical Engineering 2024;35(2):73-77
Objective The oxidative damage of DNA can be caused by excessive levels of Reactive oxygen species(ROS).Monitoring of DNA oxidative damage enables effective evaluation of ROS damage effects.Although the detection of DNA damage effects based on microbial sensor allows quantitative analysis of oxidative damage,the ROS clearance mechanism existed in bacterial will affect the sensitive of detection.The work of this article is to knockout the key genes of ROS clearance mechanism and construct an antioxidant gene-knock-out microbial sensor.The microbial sensor can realize sensitive monitoring of DNA damage effects and then evaluates the damage effects of cells by ROS.Methods The antioxidant damage genes of bacterial ahpCF,katE and katG were knocked out by λ-Red homologous recombination and antioxidant gene-knockout microbial sensor was constructed.The nalidixic acid sodium salt and UV irradiation were used to characterize the performance for monitoring of DNA damage effects.Results The antioxidant gene-knockout microbial sensors ΔahpC,ΔahpCF/ΔkatEG and ΔahpCF/ΔkatE/ΔkatG were constructed successfully.The results showed that the microbial sensor ΔahpCF/ΔkatE/ΔkatGl had the highest sensitive of damage effects and the limit of detection for nalidixic acid sodium salt was 0.40 μmol/L.In addition,1.80 min of UV irradiation(254 nm)was sufficient to induce a significant fluorescent expression effect in the engineered bacteria.Conclusion In this article,antioxidant gene-knockout microbial sensors had been constructed to realize active and sensitive monitoring of DNA damage effects such as DNA damage reagents and UV irradiation.The sensors could provide an active,effective,and sensitive potential monitoring method for future evaluation of radiation effects in space.
3.Network Pharmacology and Experimental Study of Calculus Bovis in the Treatment of Prostate Cancer
Xinjun DAI ; Yan LONG ; Bo ZOU ; Litong WU ; Junfeng QIU ; Yongrong WU ; Zhe DENG ; Yongli WANG ; Qing ZHOU ; Xuefei TIAN
World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(11):3571-3584
Objective Calculus Bovis(CB)is a kind of valuable traditional Chinese medicine,which has been used in clinic for a long time.It has been shown to have significant anti-stroke,anti-inflammatory and anti-tumor effects.But its mechanism for treating Prostate cancer(PCa)remains unclear.The purpose of this study was to explore the target and mechanism of its action in the treatment of prostate cancer throμgh network pharmacology and in vitro and in vivo experiments.Methods The effective compounds of Calculus Bovis were collected by TCM pharmacology database and analysis platform(TCMSP).Search for potential compound targets in TCMSP.Search the Drμgbank,GeneCards,OMIM,PharmGkb,and TTD databases for disease targets associated with prost cancer.Disease and compound targets were integrated in the STRING database to construct their interaction network(PPI)to reveal the key targets of compound treatment for prostate cancer.In order to elucidate the mechanism of Calculus Bovis in the treatment of prostate cancer,GO functional enrichment and KEGG pathway enrichment analysis were conducted using Cytoscape software.The mechanism of treating prostate cancer with Calculus Bovis was studied in vitro and in vivo.Results A total of 11 compounds with anti-prostate cancer activity were identified.Oleanolic acid,ursolic acid,ergosterol,deoxycorticosterone,methylcholine and cholverdin were potential effective components.A total of 367 targets of Calculus Bovis compounds and 2152 targets of prostate cancer were found.The core targets of Calculus Bovis in the treatment of prostate cancer included TP53,STAT3,AKT1,HSP90AA1,ESR1,SRC,JUN,RELA,CCND1,CDKN1A,EGFR,AR,etc.The biological functions of Calculus Bovis mainly involve oxidative stress response,response to steroid hormones,cell response to chemical stress,peptide-serine modification and phosphorylation,and protein serine/threonine kinase activity.Calculus Bovis treatment of prostate cancer mainly involves PI3K-AKT signaling pathway,TNF signaling pathway,MAPK signaling pathway,etc.In vitro and in vivo experiments showed that Calculus Bovis promoted apoptosis of PC3 cells of prostate cancer by inhibiting PI3K-AKT signaling pathway.Conclusion Calculus Bovis has a therapeutic effect on prostate cancer,and its function is related to inhibiting PI3K-AKT signaling pathway and promoting apoptosis of cancer cells.
4.Research progress on prediction of lymph node metastasis in non-small cell lung cancer
Yang WANG ; Yifan ZHONG ; Jiajun DENG ; Yunlang SHE ; Xuefei HU ; Chang CHEN
Chinese Journal of Thoracic and Cardiovascular Surgery 2022;38(7):434-440
Accurately predicting the risk of mediastinal lymph node metastasis before surgery is of great significance for tumor staging, treatment plan decision, and prognosis evaluation in patients with non-small cell lung cancer(NSCLC). Traditional imaging methods such as CT, MRI and PET/CT are currently the most commonly used clinical methods in clinical evaluation of lymph node status. However, it is subjective to judge lymph node metastasis only by the change of image morphological characteristics, and inflammatory lymphadenopathy will also lead to a high false positive rate. The clinicopathological characteristics obtained by analyzing the clinical data of patients with NSCLC can improve the accuracy of lymph node metastasis prediction to a certain extent. The clinical prediction model based on medical images combined with the clinical characteristics of patients can provide more intuitive and rational information for doctors and patients, but the performance and applicability of the model will inevitably decrease due to changes in disease risk factors and treatment measures. In recent years, with the significant improvement of image analysis technology and computing ability, radiomics models based on medical images can deeply dig into the data in radiological images for quantitative analysis, providing new ideas for predicting mediastinal lymph node metastasis in NSCLC patients, which has attracted extensive attention at home and abroad. This article reviews the progress and makes prospects of the above methods in the prediction of mediastinal lymph node metastasis in NSCLC.
5.Niuhuang (Bovis Calculus)-Shexiang (Moschus) combination induces apoptosis and inhibits proliferation in hepatocellular carcinoma via PI3K/AKT/mTOR pathway
NING Dimin ; DENG Zhe ; WU Yongrong ; MEI Si ; TENG Yongjie ; ZHOU Qing ; TIAN Xuefei
Digital Chinese Medicine 2022;5(1):83-92
Objective To investigate the effects of Niuhuang (Bovis Calculus, BC) and Shexiang (Moschus) (BC-Moschus) on human hepatocellular carcinoma (HCC) cells SMMC-7721 and a nude mouse model of subcutaneous xenografts, and to explore its anti-HCC mechanism. Methods The BC-Moschus combination was applied to two liver cancer models in vivo and in vitro. SMMC-7721 was divided into the BC-Moschus group and the control group, and different doses (rude drug dosage 0.625, 1.25, 2.5, and 5 mg/mL) of BC-Moschus extract were used for the intervention. The proliferation ability of HCC cells was detected using the Cell Counting Kit-8 (CCK-8) assay, and the migration ability was detected by a wound healing assay. A subcutaneous xenograft model was prepared using nude mice with human HCC. Specific pathogen-free-grade BALB/c nude mice (5-week-old) were randomly divided into the following groups (n = 6 per group): control (0.9% physiological saline 0.2 mL/d), BC-Moschus [BC 45.5 mg/(kg·d)+ Moschus 13 mg/(kg·d)], and cisplatin (DDP, intraperitoneal injection 5 mg/kg per week) groups. All groups were administered for 14 d. The volume and mass of the subcutaneous xenografts in nude mice were observed. The expression levels of phosphatidylinositol-3 kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway, apoptosis-associated factor p70 S6 Kinase (S6K), Bax, Bcl-2, caspase-3, and caspase-9 in nude mice subcutaneous xenografts were measured by real-time quantitative PCR (RT-qPCR) and Western blot. Terminal Deoxynucleotidy Transferase-Mediated dUTP Nick-End Labeling (TUNEL) was used for quantitative analysis of apoptotic cells. Results The CCK-8 assay demonstrated that the BC-Moschus combination inhibited HCC cell proliferation in a superior manner to the use of BC and Moschus alone, and the inhibition effect was dose- and time-dependent (P < 0.01). The wound healing assay showed that the BC-Moschus combination inhibited HCC cell migration (P < 0.01). In the subcutaneous xenograft model of nude mice with human HCC, we found that the tumor volume and weight of the BC-Moschus group were lower than those of the control group (P < 0.01). The levels of the PI3K/AKT/mTOR signaling pathway and S6K protein in the BC-Moschus and DDP groups were significantly decreased (P < 0.01). The expression level of the anti-apoptotic gene Bcl-2 was downregulated (P < 0.05), and the expression of the pro-apoptotic gene Bax and apoptosis-related factors caspase-3 and caspase-9 were significantly upregulated (P < 0.01). The TUNEL assays further confirmed that the combination of the BC-Moschuas could promote HCC (P < 0.01). Conclusion The BC-Moschus combination inhibited the proliferation and migration ability of HCC cells SMMC-7721 and effectively inhibited the growth of subcutaneous xenografts in nude mice. The mechanism may be closely related to the downregulation of the PI3K/AKT/mTOR pathway, regulation of apoptosis-related protein caspase-3, caspase-9, Bcl-2, and Bax expression, and promotion of apoptosis.
6.Protective effect of cordycepin on cardiac function in aged rats and its mechanism
Forong He ; Chi Chen ; Yuanyuan Pan ; Shengnan Deng ; Yong Shi ; Xuefei Tao
Acta Universitatis Medicinalis Anhui 2022;57(4):523-528
Objective:
To investigate the protective effect of cordycepin( Cor) on cardiac function in aged rats and its mechanism.
Methods :
The aged rats were divided into Model group,Cor administration group ( Cor 5,10,20g / kg) ,and young rats were used as Control group ( Control) .The levels of heart rate (HR) ,left ventricular e- jection fraction (LVEF) and fractional shortening (FS) were detected by echocardiography.The levels of creatine kinase MB ( CK-MB) ,myohemoglobin (Mb) ,cardiac troponin Ⅰ (cTnI) ,superoxide dismutase (SOD) ,malon- dialdehyde (MDA) and lactate dehydrogenase ( LDH) were detected by ELISA.The pathological morphology of heart tissue was observed by HE staining. The apoptosis of myocardial cells was observed by TUNEL staining. Western blot detected the protein expression of cysteine aspartic protease 9 ( Caspase 9) ,cleaved cysteine aspartic protease 9 (cleaved Caspase 9) ,cysteine aspartic protease 3 ( Caspase 3 ) ,cleaved cysteine aspartic protease 3 ( cleaved Caspase 3) ,nuclear factor E2 related factor 2 (Nrf2) ,phosphorylation nuclear factor E2 related factor 2 (p-Nrf2) ,quinone oxidoreductase 1 (NQO1) ,heme oxygenase 1 ( HO-1) .
Results :
Compared with the elderly model group,HR , LVEF ,FS increased ,CK-MB ,Mb ,cTnI levels decreased ,MDA ,LDH content decreased, SOD activity increased,cleaved Caspase 9 / Caspase 9,cleaved Caspase 3 / Caspase 3 expression decreased,The ex- pressions of Nrf2,NQO1 and HO-1 were increased,and the pathological morphology of cardiac tissue and myocar- dial apoptosis were improved in Cor groups.
Conclusion
Cor can improve cardiac function of elderly rats,relieve oxidative stress response,inhibit myocardial cell apoptosis and have a certain protective effect on cardiac tissue in- jury in rats,and the mechanism may be related to the promotion of Nrf2 / HO-1 pathway related protein expression.
7.Pharmacokinetic parameters of dynamic contrast enhanced MRI in differential diagnosis of primary central nervous system lymphoma and glioblastoma
Yu ZHANG ; Qian ZHANG ; Xiangwei LUO ; Xuefei DENG ; Youzhi ZHU
Chinese Journal of Medical Imaging Technology 2017;33(11):1630-1635
Objective To explore the difference of pharmacokinetic parameters derived from dynamic contrast enhanced (DCE) MRI between primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM).Methods Data of 17 patients with PCNSL and 21 patients with GBM were retrospectively analyzed.All patients underwent DCE MRI.The pharmacokinetic parameters (K,Kep,Ve) and the initial (60 s) area under the Gd concentration-time curve (iAUC) of peri-tumoral parenchymas (PT),enhancement tumors (ET) and contralateral normal parenchyma (NP) were obtained.The differences of various parameters were compared among different regions of PCNSL and GBM using one-way ANOVA.The differences of various parameters of PT,ET and NP were compared using independent samples t-test.Results There were statistical differences of K,Kep in ET,Kep in PT between PCNSL and GBM patients (all P<0.05),as well as of K,Kep,Ve,iAUC in PCNSL and GBM patients between ET and PT (all P<0.05).However,K and Kepof PT showed statistical differences compared with those of NP in GBM patients (both P<0.05),so did Ktrans between PT and NP in PCSL patients (P<0.05).Conclusion The pharmacokinetic parameters derived from DCE MRI based on extended Tofts Linear can promote differential diagnosis between PCNSL and GBM.
8.Effect of QCC activities on increasing early neonatal contact rate of mother and early breast sucking rate
Haidan CHENG ; Airong BAO ; Yanhui LYU ; Xue ZHAO ; Xinhui ZHUO ; Xuefei WANG ; Yan DENG
Chinese Journal of Modern Nursing 2016;22(19):2733-2736,2737
Objective To explore the effect of quality control circle ( QCC) activities on increasing early neonatal contact rate of mother and early breast sucking rate .Methods Set up a QCC,then follow the steps of QCC with professional tools to solve existing problems in early skin-to-skin contact for mothers and their healthy newborn infants and early breast sucking .Rate was compared before and after the improvements .Results The early neonatal contact rate of mother and early breast sucking rate increased from 80.94% to 93.57%,and the difference was significant (χ2 =35.07,P<0.001).Conclusions The application of the quality improvement tool of QCC could improve the early skin-to-skin contact for mothers and their healthy newborn infants and early breast sucking , and helps the mother to breastfeed successfully .
9.Exogenous hydrogen sulfide inhibits expression of tissue factor induced by ox-LDL through reducing generation of ROS and inhibiting NF-κB activation in endothelial cells
Huafei DENG ; Zhong REN ; Weijun TANG ; Xuefei LI ; Yulin TAN ; Zhihan TANG ; Lushan LIU ; Zuo WANG ; Zhisheng JIANG
Chinese Pharmacological Bulletin 2014;(7):979-984
Aim To investigate the mechanism for the inhibitory effect of hydrogen sulfide on the expression of tissue factor(TF)induced by oxidative low-density lipoprotein(ox-LDL)in endothelial cells.Methods Human umbilical vein endothelial cells (HUVECs ) were treated with 50 mg·L-1 ox-LDL in the absence or presence of different concentrations of NaHS (25 , 50,100 and 200 μmol·L-1 )for 24 h.The mRNA expression and protein content of TF in HUVECs were determined by reverse transcription PCR and ELISA, respectively.The content of intracellular reactive oxy-gen species (ROS)was determined by DCFH,an oxi-dative sensitive fluorescent indicator.The activation of nuclear factor-kappaB (NF-κB)was estimated by its expression in nuclear extracts analyzed by Western blot.Results Ox-LDL induced TF mRNA expression and increased TF protein content in HUVECs.The in-crease in intracellular ROS production and the activa-tion of NF-κB were observed in HUVECs treated with ox-LDL.However,NaHS could markedly inhibit the increases in TF mRNA and protein levels induced by ox-LDL.Also the elevation of intracellular ROS pro-duction and the activation of NF-κB elicited by ox-LDL were significantly suppressed by pretreatment with NaHS.In addition,pretreatment with BAY 1 1-7082 (10 μmol·L-1 ),the inhibitor of NF-κB or N-acetyl-L-cysteine(1 mmol·L-1 ),an antioxidant,could also decrease the TF mRNA and protein level as well as ROS production and NF-κB activation induced by ox-LDL in HUVECs,similar to the effects of 200 μmol· L-1 NaHS.Conclusion The mechanism for the in-hibitory effect of H2 S on the ox-LDL- induced TF ex-pression in endothelial cells may be related to inhibi-ting intracellular ROS production and subsequently NF-κB activation.
10.Health status of senior high school graduates living at urban or suburban areas in Beijing
Xuefei SHANG ; Xiaohong DENG ; Liguang SUN ; Shuo CHEN
Chinese Journal of Health Management 2014;8(2):106-109
Objective To compare health status of senior high school graduates living as urban vs suburban areas in Beijing.Methods Wilcoxon rank sun test,Ridit analysis and fuzzy mathematics synthesis were used to evaluate body shape index,physical function index and health defects indicator of 39 982 senior high school graduates in Beijing.Results A total of 9 117 urban boys,9 299 suburban boys,10 380 urban girls and 11 186 suburban girls were studied.For the boys,the urban was superior to the suburban areas in body shape index (Rurt=0.518,Rsub=0.482,P<0.05) and physical function index (Rurt=0.520,Rsub=0.480,P<0.05),and the urban was inferior to suburban areas in health defects indicator (Rurb=0.501,Rsub=0.554,P<0.05) and the composite index (Ruurb=0.484,Rsub=0.516,P<0.05).For the girls,the urban was superior to the suburban areas in physical function index (Rurb=0.562,Rsob=0.442,P<0.05),and the urban was inferior to the suburban areas in health defects indicator (Rurb=0.473,Rsub=0.523,P<0.05).The differences between urban and suburban areas tended to be of no statistical significance in body shape (U=5.79,P>0.05) and composite index (U=5.73,P>0.05).In fuzzy mathematics synthesis,the scores of urban boys,suburban boys,urban girls and suburban girls were 68.37,69.13,69.83 and 69.79,respectively.Conclusion Our investigation identified some differences in body shape index,physical function index and health defects indicator among senior high school graduates living at urban vs.suburban areas,although the differences of synthetical health were not statistically significant.


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