1.Effects and mechanism of persimmon leaf extract on IEC-6 cell ferroptosis induced by H2O2
Xuexia ZHANG ; Min ZHOU ; Hongyan ZHOU ; Lifei WANG ; Huani LI ; Changhe LIU ; Hongde XU ; Mingli ZHANG
China Pharmacy 2025;36(1):64-70
OBJECTIVE To investigate the effects and potential mechanism of persimmon leaf (PL) extract against ferroptosis induced by H2O2 in IEC-6 cells. METHODS Using IEC-6 cells as object, the effects of ferroptosis inhibitor ferrostatin-1 on IEC-6 cell viability induced by H2O2 were investigated; IEC-6 cells were divided into control group, H2O2 group, H2O2+PL 25 μg/mL group and H2O2+PL 50 μg/mL group. The levels of oxidant stress indexes [content of malondialdehyde (MDA), activity of superoxide dismutase (SOD), and levels of reactive oxygen species (ROS)], mitochondrial membrane potential (MMP) as well as mRNA and protein expressions of nuclear factor-erythroid-2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NADPH/quinone oxidoreductase-1 (NQO-1), cystine/glutamate anti-porter (xCT), glutathione peroxidase 4 (GPX4) and ferritin heavy chain (FTH) were detected. RESULTS Ferroptosis inhibitor ferrostatin-1 could significantly increase the survival rate of H2O2-induced cells (P< 0.01). Compared with the control group, MDA content, ROS level, mRNA expressions of Nrf2 and NQO-1 as well as protein expressions of Nrf2 and HO-1 were increased or up-regulated significantly, while SOD activity, MMP, mRNA expressions of xCT, GPX4 and FTH as well as protein expressions of GPX4 and FTH were decreased or down-regulated significantly (P<0.01 or P<0.05). Compared with the H2O2 group, oxidative stress Δ indexes of H2O2+PL 25, 50 μg/mL groups were reversed to different extents, MMP level was increased significantly, as well as mRNA and protein expressions of Nrf2, HO-1, NQO-1,xCT, GPX4 and FTH were up-regulated to different extents;there were statistical significances in some indexes between groups (P<0.01 or P<0.05). CONCLUSIONS PL extract can alleviate mitochondrial membrane damage and abnormal accumulation of ROS caused by H2O2, which may be related to the inhibition of ferroptosis by activating the Nrf2/HO-1 signaling pathway.
2.Stress analysis of computer aided design/computer aided manufacture post-core materials with different elastic moduli
Liangwei XU ; Xitian TIAN ; Lin CHEN ; Hongyan GAO ; Xian ZHU ; Guican YANG ; Yinghao CHEN
Chinese Journal of Tissue Engineering Research 2025;29(10):2061-2066
BACKGROUND:Post and core restoration is a common choice for tooth defects,but the repair effects of various post and core materials are different. OBJECTIVE:To evaluate the stress distribution at the post and core,tooth root,and bonding agent site of post and core models made of different elastic modulus post and core materials using finite element method. METHODS:A three-dimensional root canal treated maxillary central incisor model was built using three-dimensional modeling software,which was restored with a full ceramic crown.The post and core materials in the restoration used nanoceramic resin(elastic modulus=12.8 GPa),composite resin(elastic modulus=16 GPa),hybrid ceramic(elastic modulus=34.7 GPa),glass ceramic(elastic modulus=95 GPa),titanium alloy(elastic modulus=112 GPa),and zirconia(elastic modulus=209.3 GPa).The model was fixed in cortical bone.A 100 N concentrated force of 45° from the long axis of the tooth was applied to 1/3 of the crown and tongue side of the central incisor.The stress distribution of the post and core,dentin,and tooth-root bonding agent in the model was repaired by the maximum principal stress criterion. RESULTS AND CONCLUSION:(1)When the post and core materials with higher elastic modulus was used,the post-core stress in the repair model was more concentrated.When the elastic modulus of the post and core materials(nanoceramic resin and composite resin)was close to dentin,the stress distribution of the post and core was more uniform.The stress distribution of dentin in all restoration models was similar regardless of post and core materials.When the post and core with higher elastic modulus was used,more stress concentration was shown at the post and root bonding agent in the repair model.(2)The maximum stress values at the post and core,tooth root,and the bonding agent site of post and tooth root in the nanoceramic resin model were 31.00,33.21,and 0.51 MPa,respectively.The maximum stress values at the post and core,tooth root,and the bonding agent between the post and tooth root in the composite resin model were 36.84,33.14,and 0.59 MPa,respectively.In the mixed ceramic model,the maximum stress values at the post and core,tooth root,and the bonding agent between the post and tooth root were 64.05,32.83,and 1.00 MPa,respectively.In the glass ceramic model,the maximum stress values at the post and core,tooth root,and the bonding agent between the post and tooth root were 112.30,32.69,and 1.73 MPa,respectively.In the titanium alloy model,the maximum stress values of the post and core,tooth root,and the bonding agent between the post and tooth root were 120.00,32.17,and 1.86 MPa,respectively.In the zirconia model,the maximum stress values of the post and core,tooth root,and the bonding agent between the post and tooth root were 148.80,31.85,and 2.28 MPa,respectively.(3)The higher the elastic modulus of the post and core material,the higher the maximum stress at the post and core during restoration.The elastic modulus of the post and core material had no significant effect on the maximum stress of the dental bonding agent and dentin.
3.Value of FibroScan, gamma-glutamyl transpeptidase-to-platelet ratio, S index, interleukin-6, and tumor necrosis factor-α in the diagnosis of HBeAg-positive chronic hepatitis B liver fibrosis
Yingyuan ZHANG ; Danqing XU ; Huan MU ; Chunyan MOU ; Lixian CHANG ; Yuanzhen WANG ; Hongyan WEI ; Li LIU ; Weikun LI ; Chunyun LIU
Journal of Clinical Hepatology 2025;41(4):670-676
ObjectiveTo investigate the value of noninvasive imaging detection (FibroScan), two serological models of gamma-glutamyl transpeptidase-to-platelet ratio (GPR) score and S index, and two inflammatory factors of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in predicting liver fibrosis in patients with HBeAg-positive chronic hepatitis B (CHB), as well as the consistency of liver biopsy in pathological staging, and to provide early warning for early intervention of CHB. MethodsA retrospective analysis was performed for 131 HBeAg-positive CHB patients who underwent liver biopsy in The Third People’s Hospital of Kunming from January 2019 to December 2023. The results of liver biopsy were collected from all patients, and related examinations were performed before liver biopsy, including total bilirubin, alanine aminotransferase, platelet count, gamma-glutamyl transpeptidase, albumin, IL-6, TNF-α, liver stiffness measurement (LSM), and abdominal ultrasound. An analysis of variance was used for comparison of normally distributed continuous data between groups, and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. A Kappa analysis was used to investigate the consistency between LSM noninvasive histological staging and pathological staging based on liver biopsy, and the Spearman analysis was used to investigate the correlation between each variable and FibroScan in the diagnosis of liver fibrosis stage. The Logistic regression analysis was used to construct joint predictive factors. The receiver operating characteristic (ROC) curve was used to evaluate the value of each indicator alone and the joint predictive model in the diagnosis of liver fibrosis, and the Delong test was used for comparison of the area under the ROC curve (AUC). ResultsIn the consistency check, inflammation degree based on liver biopsy had a Kappa value of 0.807 (P<0.001), and liver fibrosis degree based on liver biopsy had a Kappa value of 0.827 (P<0.001), suggesting that FibroScan noninvasive histological staging and liver biopsy showed good consistency in assessing inflammation degree and liver fibrosis stage. Age was positively correlated with LSM, GPR score, S index, IL-6, and TNF-α (all P<0.05), and GPR score, S index, IL-6, and TNF-α were positively correlated with LSM (all P<0.05). GPR score, S index, IL-6, and TNF-α were all independent risk factors for diagnosing significant liver fibrosis (≥S2) and progressive liver fibrosis (≥S3) (all P<0.05). As for each indicator alone, GPR score had the highest value in the diagnosis of significant liver fibrosis (≥S2), followed by S index, IL-6, and TNF-α, while S index had the highest value in the diagnosis of progressive liver fibrosis (≥S3), followed by GPR score, TNF-α, and IL-6. The joint model had a higher predictive value than each indicator alone (all P<0.05). ConclusionThere is a good consistency between FibroScan noninvasive histological staging and pathological staging based on liver biopsy. GPR score, S index, IL-6, and TNF-α are independent risk factors for evaluating different degree of liver fibrosis in CHB, and the combined prediction model established by them can better diagnose liver fibrosis.
4.Association between preschoolers physical activity levels and parental sports concept and behavior
Chinese Journal of School Health 2024;45(7):1036-1039
Objective:
To analyze the impact of parental sports concept and behavior on physical activity in preschool children, so as to provide a foundation for future guidance on fostering childrens physical activity within the family context.
Methods:
From November to December 2020, a clustered convenience sampling method was employed to conduct surveys, and a total of 283 children were selectal from one kindergarten each in Beijing, Shenyang, and Xian. Participating children wore ActiGraph GT9X accelerometers continuously for one week to collect data on different intensity levels of physical activity. Physical Activity afterschool Questionnaire for Preschooler (P-PAQ) was utilized to assess parental sports concept and behavior. The gender differences in physical activity level and physical activity compliance rate were analyzed by using ttest, Mann-Whitney U test, and Chisquare test; and the relationship between parental exercise concepts and behaviors and physical activity of preschool children was analyzed using Spearman rank correlation analysis and multiple linear regression analysis.
Results:
Parental sports concept was significantly positively correlated with average daily moderatetovigorous physical activity (MVPA) and total physical activity (TPA) in children (r=0.12-0.16, P<0.05). Parental sports behavior was significantly positively correlated with childrens average daily TPA (r=0.25, P<0.05). Multiple linear regression revealed that parental sports concept was positively correlated with average daily MVPA and TPA in both boys and girls (B=0.65-0.83), while parental sports behavior only was positively correlated with boys average daily MVPA and TPA (B=0.24-0.25)(P<0.05).
Conclusions
Parental sports concept and behavior can impact physical activity levels in preschool children, exhibiting gender differences. Future guidance on physical activity in family upbringing should consider both parental sports concept and behavior, and pay attention to the influence of childrens gender.
5.The Multicenter Cross-sectional Study on the Distribution Characteristics of Traditional Chinese Medicine Syndrome Elements in Type 2 Diabetes Macroangiopathy
Yulin LENG ; Hong GAO ; Xiaoxu FU ; Gang XU ; Hongyan XIE ; Xingwei ZHUO ; Xiaoqin ZHOU ; Yi YANG ; Xiaoli YUAN ; Zhibiao WANG ; Chunguang XIE
Journal of Traditional Chinese Medicine 2024;65(17):1794-1801
ObjectiveTo explore the distribution characteristics of traditional Chinese medicine (TCM) syndrome elements of macroangiopathy in patients with type 2 diabetes mellitus (T2DM) and the key elements of occurrence, development and progression of disease. MethodsA multicenter cross-sectional study was conducted to enroll 445 T2DM patients from five hospitals, and according to the presence or absence of macroangiopathy, the patients were divided into a T2DM group (120 cases) and a diabetic macroangiopathy (DM) group (325 cases). Patients in DM group were divided into grade Ⅰ, Ⅱ, Ⅲ and Ⅳ according to the peripheral vascular color Doppler ultrasound results and the vascular anomalies classification standard. The general data including gender, age, duration of T2DM and body mass index (BMI) were collected, and the data of four examinations were obtained for syndrome differentiation. According to the diagnostic criteria of TCM syndrome elements, the patients can be divided into 9 patterns including qi deficiency, blood deficiency, yin deficiency, yang deficiency, qi stagnation, blood stasis, excess heat, and excess cold. The general data and distribution of TCM syndrome elements were compared between the two groups. The distribution of TCM syndrome elements in different vascular anomalies grades in the DM group was analyzed. Logistic regression analysis was used to explore the influence of various TCM syndrome elements on the occurrence of macroangiopathy in T2DM. ResultsThere was no significant difference in gender and BMI between groups (P>0.05). The age and duration of diabetes in the DM group were older and longer than those in the T2DM group (P<0.01). With the increase of age and prolonged course of disease, the severity of diabetic macroangiopathy increases gradually (P<0.05 or P<0.01). There was no significant difference in BMI and course of disease among the different TCM syndrome elements (P>0.05). The average age of patients with blood stasis syndrome was the oldest (P<0.05). There was significant difference in gender distribution between the excess heat syndrome and yin deficiency syndrome (P<0.05). A total of 240 TCM syndrome elements were extracted from the T2DM group, while 731 TCM syndrome elements extracted from the DM group. The top two high-frequency syndrome elements in the two groups were qi deficiency and yin deficiency, with a frequency of larger than 50%. The distribution of phlegm-damp syndrome and blood-stasis syndrome were significantly higher in the DM group than in the T2DM group (P<0.01). There were significant differences in the distribution of qi deficiency syndrome, yin deficiency syndrome, phlegm-damp syndrome, blood stasis syndrome, and excess heat syndrome among different grades of vascular anomalies (P<0.01); qi deficiency and yin deficiency were both high-frequency TCM syndrome elements in patients at grades 0 to Ⅲ; phlegm-damp syndrome increased in frequency with the progression of the disease from grades 0 to Ⅳ, and the frequency of blood stasis syndrome showed an overall upward trend. The frequency of phlegm-dampness syndrome increased from grades 0 to Ⅳ with the progression of the disease, and the frequency of blood stasis syndrome showed an overall upward trend. Logistic regression analysis showed that phlegm-damp syndrome and blood stasis syndrome were important TCM syndrome elements related to the vascular anomalies degree of macrovascular disease in T2DM (P<0.05 or P<0.01). ConclusionQi deficiency and yin deficiency are the basic TCM syndrome elements throughout the whole process of T2DM and diabetic macrovascular disease. Phlegm-damp and blood stasis are related to the degree of vascular anomalies in diabetic macrovascular disease and are the key TCM syndrome elements in the progression of macroangiopathy in T2DM.
6.Clinical efficacy of PDCA cycle management model cycle management combined with pulsed tooth punch applied in maintenance period of patients with moderate to severe periodontitis
Cong JIANG ; Wenzhou XU ; Hongyan LI ; Yue SUN ; Lan A
Journal of Jilin University(Medicine Edition) 2024;50(1):221-227
Objective:To observe the clinical efficacy of plan-do-check-Act(PDCA)cycle management model combined with pulsed tooth punch applied in maintenance period of the patients with moderate to severe periodontitis,and to provide the theoretical basis for application of the PDCA cycle management model in the periodontitis patients.Methods:A total of 50 patients with moderate to severe periodontitis were selected based on predefined inclusion,exclusion,and elimination criteria.The patients were randomly divided into experiment group(n=25)and control group(n=25).The patients in experiment group underwent maintenance care with pulsed tooth punch in combination with the BASS brushing technique,while the patients in control group maintained oral hygiene with the BASS brushing technique alone.The patients in both two groups were managed with the PDCA cycle management model.The patients were asked to return for follow-up visits at 2,4,8,and 12 weeks of self-care,and the personalized corrections and guidance were provided based on the plaque accumulation.The clinical periodontal parameters,including plaque index(PLI),probing depth(PD),and bleeding index(BI),at 4 and 12 weeks of self-care,as well as the levels of tumor necrosis factor-α(TNF-α)and interleukin-17(IL-17)in the gingival crevicular fluid of the patients in two groups were observed and recorded.Results:After 4 and 12 weeks of self-care,compared with control group,the PLI,PD,and BI of the patients in experiment group were significantly decreased(P<0.01);compared with baseline,the PLI,PD,and BI of the patients in both two groups at 4 and 12 weeks of self-care were increased(P<0.05 or P<0.01);Compared with 4 weeks of self-care,the PLI,PD,and BI of the patients at 12 weeks of self-care were increased(P<0.01).After 4 and 12 weeks of self-care,compared with control group,the levels of TNF-α and IL-17 in gingival crevicular fluid of the patients in experiment group were significantly decreased(P<0.01);compared with baseline,the levels of TNF-α and IL-17 in gingival crevicular fluid of the patients in two groups at 4 and 12 weeks of self-care were increased(P<0.01).Conclusion:The use of pulsed tooth punch under the PDCA cycle management model can significantly decrease the PLI,PD,BI,and the levels of inflammatory factors in gingival crevicular fluid of the patients with moderate to severe periodontitis,and inhibit the plaque formation and control the gingival inflammation,benefite the maintenance of efficacy of the patients with moderate to severe periodontitis.
7.The study on the effect of neuregulin-1 on myocardial injury in septic rats
Chao XU ; Rong HUANG ; Hongyan ZHAO ; Jing CAO
Chongqing Medicine 2024;53(2):165-170
Objective To study the effect of neuromodulatory protein-1(NRG-1)in inhibiting sepsis induced myocardial injury and its mechanism.Methods The rat sepsis model was established by cecal ligation and puncture(CLP).SD rats were divided into the sham operation group,sepsis group,sepsis+NRG group(rhNRG,10 μg/kg).After 12,24 h of successful modeling,the heart and peripheral serum of the surviving rats in each group were taken respectively.The HE staining was used to observe the changes of cardiac tissue morphology and structure,and ELISA was used to detect the expression levels of creatine kinase(CK),crea-tine kinase MB isoenzyme(CK-MB),sensitive troponin Ⅰ(cTnⅠ)in serum,tumor necrosis factor-α(TNF-α)in cardiac tissue and IL-6 expression level;Western blot was used to detect the phosphorylation protein ki-nase B(p-Akt),phosphorylation glycogen synthase kinaseβ(p-GSK3β),B-cell lymphoma/leukemia-2(Bcl-2)and Bax protein expression in rat myocardial tissue.Results After 12,24 h of modeling,compared with the sham group,the expression levels of CK,CK-MB and cTnⅠ in serum,TNF-α,IL-6 and Bax protein in myocar-dial tissue in the sepsis group all were significantly increased(P<0.05),while the expression levels of p-Akt and p-GSK3β in myocardial tissue were significantly decreased(P<0.05).After 12,24 h of modeling,com-pared with the sepsis group,the expression levels of CK,CK-MB,cTn Ⅰ in the serum and the expression levels of TNF-α,IL-6 in the myocardial tissue of the sepsis+NRG group were significantly decreased;after 24 h of modeling,compared with the sepsis group,the expression level of Bax protein in myocardial tissue of the sep-sis+NRG group was decreased,while the p-Akt,p-GSK3β expression levels were increased(P<0.05).The pathological results showed that compared with the sham operation group,the sepsis group produced signifi-cant lesions;compared with the sepsis group,the lesions in the sepsis+NRG group were alleviated.Conclusion The expression levels of related biomarkers in septic myocardial injury have change.NRG-1 could improve the cardiac function through Akt/GSK3β pathway,inhibit the related proinflammatory factors and reduce the myocardial tissue damage.
8.Clinical observation of areola approach endoscopic thyroidectomy and gasless axillary approach endoscopic thyroidectomy in the treatment of patients with papillary thyroid carcinoma
Hongyan SHEN ; Dandan HU ; Lei ZHAO ; Peiyou REN ; Guanlei ZHOU ; Zhen XU
Chinese Journal of Endocrine Surgery 2024;18(1):51-56
Objective:To explore the clinical efficacy of areola approach endoscopic thyroidectomy (AET) and gasless axillary approach endoscopic thyroidectomy (GAET) in the treatment of papillary thyroid carcinoma (PTC) patients.Methods:A total of 96 PTC patients from the Thyroid Surgery Department of Linyi People’s Hospital from May. 2019 to May. 2022 were selected and randomly divided into 48 patients using a random number table method. The areola group received AET, while the armpit group received GAET. The surgical situation, postoperative recovery, relevant biochemical indicators [white blood cell count (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), parathyroid hormone (PTH), blood calcium] before and after surgery, postoperative pain level, discomfort level, neck function, and complications were compared between the two groups.Results:The surgical time and extubation time of the armpit group were (125.71±15.73) minutes and (3.12±0.53) days, respectively, which were shorter than those of the areola group (137.94±20.02) minutes and (3.48±0.46) days. The intraoperative bleeding volume was (14.19±4.16) mL, which was less than that of the areola group (22.65±7.39) mL, and the number of lymph nodes cleaned was 5.06±1.02, which was more than that of the areola group (4.23±1.14) ( P<0.05) ; there was no significant difference in postoperative drainage volume and hospital stay between the two groups ( P>0.05) ; Peripheral blood WBC in the armpit group on the 1st and 3rd day after surgery [ (5.69±0.15) ×10 9/L, (5.52±0.14) ] ×10 9/L, ESR [ (8.21±0.55) mm/h, (7.64±0.60) mm/h], CRP [ (10.06±1.78) ng/L, (8.93±1.33) ng/L] were lower than those in the areola group [ (5.83±0.21) ×10 9/L, (5.70±0.23) ×10 9/L, (8.87±0.74) mm/h, (8.19±0.68) mm/h, (12.45±1.90) ng/L, (10.45±1.50) ng/L] ( P<0.05). There was no significant difference in the levels of the above biochemical indicators 5 days after surgery ( P>0.05). There was no significant difference in peripheral blood PTH and calcium levels between the two groups on the 1st, 3rd, and 5th postoperative days ( P>0.05). The pain level [ (3.25±0.32) scores, (2.53±0.27) scores, (1.82±0.22) scores] and discomfort level [ (6.85±0.71) scores, (5.24±0.66) scores, (3.51±0.57) scores] in the axillary group were lower than those in the areola group [ (3.78±0.40) scores, (2.89±0.34) scores, (2.06±0.26) scores, (7.46±0.84) scores, (6.09±0.73) scores, (4.16±0.60) scores] on the 1st, 3rd, and 5th postoperative days ( P<0.05). The neck flexion, lateral flexion, and extension range of motion in the axillary group on the 3rd day after surgery were (33.16±3.09) °, (27.63±2.57) °, and (30.44 2.73) °, respectively, which were greater than those in the areola group[ (30.08±2.76) °, (25.14±2.30) °, and (27.98±2.54) °], and the swallowing disorder index was (30.16±4.97) points lower than the (34.83±4.13) points in the areola group ( P<0.05). The incidence of complications in the axillary group was 4.17% (2/48), lower than the 16.67% (8/48) in the areola group. Conclusion:GAET treatment for PTC patients can improve the effect of lymph node dissection, reduce the degree of surgical trauma, postoperative pain and discomfort, accelerate early postoperative recovery of neck function, and reduce complications.
9.Effects of vesicular stomatitis virus on anti-tumour immunity, growth of xenografts, and lung metastasis in mouse mammary carcinoma 4T1 cells tumor-bearing mice
LI Yuqian1a ; XU Qingsheng1a ; WEI Hong1b ; WANG Hao2 ; WANG Shuoshi3 ; JIANG Lina1a ; YUAN Xinyi1c
Chinese Journal of Cancer Biotherapy 2024;31(5):452-461
[摘 要] 目的:探究野生型水疱性口炎病毒印第安纳株(VSV-IN)对小鼠三阴性乳腺癌4T1细胞移植模型小鼠的免疫调节及肿瘤转移的影响。方法:VSV以MOI=1、MOI=10、MOI=100感染4T1细胞12、24、48 h后,CCK-8法检测4T1细胞死亡率,划痕愈合实验检测细胞迁移能力,qPCR检测细胞中E-cadherin、MMP-2、MMP-9 mRNA的表达。于雌性BALB/c小鼠脂肪垫接种1×106个/mL的4T1细胞0.1 mL,构建4T1细胞荷瘤小鼠模型,待小鼠肿瘤体积达200 mm3,分别向移植瘤内注射PBS、紫杉醇(TAX)(15 mg/kg)、VSV-IN(1×106 pfu/只),每周1次。给药4次后,处死小鼠、剥离完整移植瘤组织,测量肿瘤体积及质量,肺组织病理切片经H-E染色后观察肿瘤肺部转移结节,流式细胞术检测脾组织中T细胞亚群比例,ELISA法检测小鼠血清IL-6及TNF-α水平,利用GEPIA在线分析乳腺肿中迁移相关蛋白mRNA的表达,免疫组化法检测肿瘤中MMP-2、MMP-9与E-cadherin的表达,利用蛋白-蛋白对接技术预测VSV-IN的G蛋白、M蛋白与ERK2、E-cadherin的亲和力。结果:经MOI=10、100的VSV-IN处理48 h后,4T1细胞死亡率显著高于对照组(均P<0.01);与对照组相比,VSV-IN组(MOI=10)细胞迁移率明显降低(P<0.01),MMP-9 mRNA的相对表达量明显降低(P<0.05);与对照组小鼠相比,VSV-IN组移植瘤生长较对照组减缓且终点体积显著减小(P<0.05),VSV-IN组小鼠肺转移结节数量显著减少[(12.86±1.86) vs (24±3.67)个,P<0.01],脾内CD4+ T、CD8+ T细胞比例显著升高(均P<0.05),血清TNF-α、IL-6含量显著升高(均P<0.01);GEPIA分析发现在乳腺癌中E-cadherin、MMP-9表达水平均高于癌旁组织(P<0.05);VSV-IN组小鼠肿瘤细胞内MMP-9表达明显低于对照组(P<0.05);VSV-IN的G、M蛋白与ERK2的结合自由能分别为–11.7 kcal/mol、–6.4 kcal/mol。结论:野生型VSV-IN可抑制4T1细胞荷瘤小鼠的移植瘤生长及转移,这可能与其促进抗肿瘤免疫及调控迁移相关蛋白表达有关。
10.Prediction and validation of potential targets for the glucagon-like peptide-1 receptor agonist in the treatment of Alzheimer's disease
Weina HAN ; Xiaoqing XU ; Jinning SHI ; Xinru LI ; Hongyan CAI
Chinese Journal of Tissue Engineering Research 2024;28(16):2568-2573
BACKGROUND:In the process of exploring the mechanism of Alzheimer's disease,the important role of bioinformatics for common target screening has been revealed,enabling the use of its screening results as a basis for exploring the therapeutic effects of drugs on the disease. OBJECTIVE:To predict the targets of liraglutide,a glucagon-like peptide-1 receptor agonist,in the treatment of Alzheimer's disease by bioinformatics and molecular biology. METHODS:DisGeNET database and SEA database were used to obtain the common genes of Alzheimer's disease and liraglutide.GO/KEGG enrichment analysis of common targets was conducted using DAVID online database.Protein-protein interaction networks were constructed using STRING database.The optimal dosage of liraglutide was determined using cell counting kit-8 assay.Expression of key proteins was analyzed using immunofluorescence and immunoblotting techniques.The mouse hippocampal neuron HT22 cell line was used for ex vivo experiments,and the cells were randomly divided into three groups:HT22 group,HT22+Aβ group,and HT22+Aβ+Lir group.No special treatment was done in the HT22 group,while Aβ1-42 was used to intervene in the HT22 cell line for 24 hours to construct an Aβ injury cell model in the HT22+Aβ group.In additional to modeling,liraglutide was added to the HT22+Aβ+Lir group for 12 hours. RESULTS AND CONCLUSION:A total of 3 333 genes associated with Alzheimer's disease were screened from DisGeNET database.Then 147 potential targets of liraglutide were obtained from SEA database.Finally,64 common targets of Alzheimer's disease and Liraglutide were determined using R packets.GO/KEGG analysis of common targets using DAVID online database suggested that common targets were mainly enriched in the following biological processes:neuroactive ligand-receptor interaction,renin-angiotensin system,bladder cancer,endopeptidase activity,peptide receptor activity,G protein-coupled peptide receptor activity,and transport vesicles.The obtained 64 common target proteins were imported into SRTING online database for protein-protein interaction network construction,and the top three genes,matrix metalloproteinases 2,9 and interleukin 1β,were obtained.The activity of cultured cells was detected by the cell counting kit-8 kit.Liraglutide at 100 nmol/L was the optimal concentration for antagonizing Aβ1-42.In the western blot and immunofluorescence assays,the expression of matrix metalloproteinases 2,9 and interleukin 1β was significantly increased in the HT22+Aβ group compared with the HT22 group(P<0.05)but significantly decreased in the HT22+Aβ+Lir group compared with the HT22+Aβ group(P<0.05).To conclude,the above bioinformatics data and secondary validation of differential genes in the GEO database suggest that both matrix metalloproteinases 2,9 and interleukin 1β could be potential targets of liraglutide in the treatment of Alzheimer's disease.


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