1.CircRNA Circ_0120051 Inhibits the Fibrotic Phenotype of Myocardial Fibroblasts via Targeting miR-144-3p/IDH2 Axis
Yu LIANG ; Zhiqin HU ; Yihong WEN ; Huayan WU ; Ya WNAG ; Yupeng LIU ; Zhixin SHAN ; Xianhong FANG
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(2):196-205
ObjectiveTo investigate the regulatory effect of circular RNA circ_0120051 on the fibrotic phenotype of cardiac fibroblasts and the potential mechanism involved. MethodsThe expression of circ_0120051 and its host gene of solute carrier family 8 member A1(SLC8A1) mRNA in the myocardium of healthy organ donors (n=24) and heart failure (HF) patients (n=21) were assessed by real-time quantitative polymerase chain reaction (RT-qPCR) assay. RNA stability of circ_0120051 was identified by RNase R exonuclease digestion assay. The cytoplasmic and nuclear distribution of circ_0120051 in human cardiomyocyte AC16 was detected by RT-qPCR assay. The expression of fibrosis-related genes in mouse cardiac fibroblasts (mCFs) with adenovirus-mediated overexpression of circ_0120051 was detected by RT-qPCR and Western blot assay, respectively. The effect of overexpression of circ_0120051 on the migration activity of mCFs was evaluated by wound-healing assay. RNA co-immunoprecipitation (RIP) was conducted to detect the interaction between circ_0120051 and miR-144-3p. The binding site of miR-144-3p in the 3'-UTR of isocitrate dehydrogenase 2 (Idh2) mRNA was identified by the dual luciferase reporter gene assay. ResultsCirc_0120051 was significantly up-regulated in the myocardium of HF patients, while the mRNA expression of its host gene SLC8A1 was not changed. Circ_0120051 was mainly located in the cytoplasm of human AC16 cells. Results of RNase R exonuclease digestion revealed that circ_0120051 possesses the characteristic stability of circular RNA compared to the linear SLC8A1 mRNA. Overexpression of circ_0120051 could inhibit the expression of fibrosis-related gene in mCFs and mCFs migration. RIP assay confirmed the specific interaction between circ_0120051 and miR-144-3p. Transfection of miR-144-3p mimic could efficiently promote the expression of fibrosis-related genes in mCFs and reverse the inhibitory effect of circ_0120051 on the fibrotic phenotype of mCFs. Results of the dual luciferase reporter gene assay confirmed the interaction between miR-144-3p and the 3'-UTR of Idh2. Transfection of miR-144-3p transcriptionally inhibited Idh2 expression, and overexpression of circ_0120051 enhanced IDH2 expression in mCFs. MiR-144-3p mimic and Idh2 small interfering RNA (siRNA) could consistently reverse the inhibitory effects of circ_0120051 on fibrosis-related genes expression in mCFs and mCFs migration. ConclusionsCirc_0120051 inhibits the fibrotic phenotype of cardiac fibroblasts via sponging miR-144-3p to enhance the target gene of IDH2 expression.
2.Effect of Shenqi Pills (肾气丸) on Cognitive Function and Hippocampal Glucose Energy Metabolism in Type 2 Diabetes Mellitus Model Mice
Shan ZHANG ; Zhige WEN ; Yueying ZHANG ; Yanan YANG ; Tianjie BU ; Yupeng CHEN ; Qing NI
Journal of Traditional Chinese Medicine 2023;64(19):2010-2018
ObjectiveTo explore the effect and possible mechanism of Shenqi Pills (肾气丸) on cognitive impairment and hippocampal glucose energy metabolism in type 2 diabetes mellitus (T2DM). MethodsSixty C57BL/6 mice were randomly divided into control group, model group, rosiglitazone group and Shenqi Pills low-, medium- and high-dose groups, with 10 mice in each group. T2DM model was induced by a high-fat diet combined with intraperitoneal injection of streptozotocin in all the groups except for the control group. After successful modeling, the high-, medium-, and low-dose Shenqi Pills groups were given 2.08, 1.04, and 0.52 g/(kg·d) of Shenqi Pills granules by gavage respectively, while the rosiglitazone group was given 3 mg/(kg·d) of rosiglitazone tablets by gavage, and the control group and model group were gavaged with 10 ml/(kg·d) of distilled water, all for 8 consecutive weeks. The body weight and fasting blood glucose (FBG) level were recorded every two weeks. The Morris water maze test was performed on the 8th week of medication. After 8-week medication, oral glucose tolerance test (OGTT) and fasting insulin level were measured, hippocampal glucose energy metabolism-related products were quantitatively detected by liquid chromatography tandem mass spectrometry, and KEGG annotation analysis was performed. ResultsCompared to those measured at the same timepoints in the control group, the body mass on week 6 and 8, as well as the FBG level on week 2, 4, 6 and 8 in the model group increased; the blood glucose level at 0, 30, 60 and 120 minutes of the OGTT test increased, while fasting insulin level after 8-week medication decreased. The escape latency of the model group was significantly prolonged on the 3rd and 4th days, and the escape latency time increased, while the total swimming distance, platform quadrant residence time and the number of platform crossings decreased (P<0.05 or P<0.01). Compared to those measured at the same timepoints in the model group, the body mass on week 6 in the low-dose Shenqi Pills group, on week 6 and 8 in the medium- and high-dose groups, and on week 8 in the rosiglitazone group were significantly reduced; the FBG levels in all the Shenqi Pills groups and rosiglitazone group on week 6 and 8 decreased, while fasting insulin levels increased. In the OGTT test, blood glucose in the medium-dose group of Shenqi Pills at all timepoints decreased; in the Morris water maze test, the escape latency period of the medium- and high-dose Shenqi Pills groups was shortened on the 3rd and 4th days, while the escape latency time was reduced, and the total swimming distance, platform quadrant residence time, and number of platform crossings increased in the medium-dose Shenqi Pills group (P<0.05 or P<0.01).The medium-dose Shenqi Pills showed best effect, therefore it was selected for the targeted quantitative detection of metabolites. The medium-dose Shenqi Pills group could regulate the disorder of glucose metabolism in the hippocampus of T2DM mice, and 13 differential metabolites were found,up-regulating α-ketoglutarate and 3-phosphoglyceric acid, and down-regulating fumaric acid, glutamatic acid, lactatic acid, inosine, malic acid, adenine, fructose 1,6-diphosphate and others. KEGG annotation of differential metabolites suggested that Shenqi Pills was closely related to the regulation of glucose metabolism disorder and insulin resistance in the hippocampus region of T2DM model mice, as well as neurodegenerative diseases and ABC transport, hypoxia-inducible factor 1 (HIF), forkhead transcription factor (FoXO) and cyclic adenosine monophosphate (cAMP) signaling pathways. ConclusionShenqi Pills can improve learning and memory abilities and cognitive impairment in T2DM mice, and may act its role by regulating glucose energy metabolism in the hippocampus of T2DM.
3.Effect of IGF1Rβ Subunit Mutants on Proliferation, Migration and Apoptosis of Human Osteosarcoma Cells
Zhongchi1 WEN ; Tuozhou1 LIU ; Hongbo HE ; Can ZHANG ; Yupeng LIU ; Zhan LIAO ; Liyi ZENG
Cancer Research on Prevention and Treatment 2022;49(5):390-395
Objective To investigate the effect of IGF1R β subunit mutants sb-IGF1R and ma-IGF1R on the biological behavior of osteosarcoma 143B cells. Methods We designed and constructed sb-IGF1R and ma-IGF1R fragments. They were cloned into adenovirus AdEasy shuttle plasmid, to obtain Ad-sbIGF1R and Ad-maIGF1R. We observed the proliferation, migration and apoptosis of the osteosarcoma cells transfected with Ad-sbIGF1R, Ad-maIGF1R and Ad-IGF1R. The Ad-sbIGF1R, Ad-maIGF1R and Ad-GFP nude mouse models were constructed to evaluate the tumor growth
4.Clinical experiences of the surgical treatment of severe ventricular septal defect and pulmonary hypertension in little infants
Yupeng WEN ; Zongxiao LI ; Cheng CHANG ; Peng ZHANG
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2018;25(2):215-217
Objective To summarize the experience of surgical treatment of severe ventricular septal defect (VSD) accompanied by pulmonary hypertension (PH) in little infants. Methods The clinical data of 11 patients with VSD accompanied by PH admitted to the Department of Cardiac Surgery of Tianjin Children's Hospital of the Pediatric Clinical College in Tianjin Medical University from January 2016 to January 2017 were retrospectively analyzed. There were 6 males and 5 females, with the ages of 3 - 6 months, mean (5.36±1.03) months and body weights 4.2 - 7.5 kg, mean (5.9±1.0) kg. Preoperatively, all patients had recurrent pneumonia and heart failure history. After 2 - 3 times of medical treatment in hospitals, the patients underwent sub-acute radical operation under cardiopulmonary bypass. All patients were followed-up with echocardiography, chest X-ray and electrocardiogram examinations at 3, 6 and 12 months after heart surgery. Results After operation, all the children spontaneously recovered the heart beats, the stay times in surgical intensive care unit (SICU) were 2 - 7 days, and total hospitalization times were 12 - 17 days. All patients were followed up for 12 months, no death occurred in the whole group, and the heart and lung functions recovered satisfactorily. Conclusions Little infants with large VSD and PH should undertake operation as early as possible. The patients with recurrent pneumonia, heart failure in a short term should receive medical and surgical doctors' cooperative treatment, and the disease situation ought to be adjusted with one's best ability to a stable status when the sub-acute surgery can be carried out safely.
5.Relationship of MyD88 rs7744 Polymorphism with the Risk and Severity of Coronary Artery Disease
Dandan SUN ; Yupeng WU ; Wen LIU ; Hong YAN ; Honghu WANG ; Jun YANG
Journal of China Medical University 2017;46(6):519-523
Objective To investigate the association between rs7744 polymorphism in the 3'?untranslated region(3'?UTR)of myeloid differen?tiation factor 88(MyD88)gene and the risk and severity of coronary artery disease(CAD)in a North Chinese Han population. Methods The CAD and control groups consisted of 540 patients and 270 subjects,respectively. The genotypes of rs7744 were detected by polymerase chain reac?tion?restriction fragment length polymorphism(PCR?RFLP),and clinical data were collected. Results The distributions of MyD88 rs7744 were in HWE(P>0.1). In the<50?year?old age group,a lower risk of CAD was observed for subjects carrying the variant AG genotype in comparison to subjects carrying the wild AA genotype(OR=0.38,95%CI:0.17-0.93,P=0.029). The MyD88 rs7744 polymorphism was also related to the modified Gensini score(P=0.011),which was lower in subjects carrying the variant GG genotype than the wild AA genotype(5.23±3.85 vs 7.49± 4.96). Conclusion Our results revealed that MyD88 rs7744 polymorphism in the 3'?UTR is correlated with the risk and severity of CAD.
6.Diagnostic significance of urinary neutrophil gelatin enzyme-related lipid delivery protein and kidney injury molecule-1 in acute kidney injury after cardiac operation with cardiopulmonary bypass operation in children
Yupeng WEN ; Zongxiao LI ; Cheng CHANG ; Peng ZHANG ; Yang LYU
Chinese Critical Care Medicine 2017;29(12):1112-1116
Objective To investigate the diagnostic value of urinary neutrophil gelatin enzyme-related lipid delivery protein (NGAL) and kidney injury molecule-1 (KIM-1) in the acute kidney injury (AKI) after cardiopulmonary bypass (CPB) operation in children with non-cyanotic congenital heart disease (CHD). Methods A retrospective analysis was conducted. 200 CPB undergoing cardiac surgery in children with non-cyanotic CHD admitted to Tianjin Children's Hospital from June 2015 to May 2017 were enrolled. All patients were divided into AKI group and non-AKI group within 48 hours after operation, and the two groups matched with age, sex, weight, basic complications, operation time and other factors. The differences in serum creatinine (SCr), urinary NGAL and KIM-1 [corrected for urinary creatinine (UCr)] between the two groups before and after operation were compared. The early diagnosis value of urinary NGAL and KIM-1 on AKI was analyzed by the receiver operating characteristic curve (ROC). Results There were 32 patients with different degrees of AKI 48 hours post operation, and the incidence was 16.0%; 60 cases were enrolled in non-AKI group. Compared with non-AKI group, urinary NGAL at 2 hours after operation, urine KIM-1 at 4 hours after operation, and SCr at 10 hours after operation in AKI group were significantly increased, which decreased gradually after reaching peak at 6, 8, 24 hours respectively. It was shown by ROC curve analysis that the area under ROC curve (AUC) and 95% confidence interval (95%CI) of postoperative 2-hour urine NGAL, 4-hour urine KIM-1 and 10-hour SCr for diagnosis of AKI were 0.940 (95%CI = 0.890-0.990), 0.939 (95%CI = 0.891-0.986) and 0.959 (95%CI = 0.916-1.000) respectively. When the cut-off value of postoperative 2-hour urine NGAL was 588.0 μg/g, the sensitivity was 87.5%, the specificity was 95.0%, the accuracy was 93.5%; when the cut-off value of postoperative 4-hour urine KIM-1 was 9.55 ng/mg, the sensitivity was 87.5%, the specificity was 91.7%, the accuracy was 90.2%; and when the cut-off value of postoperative 10-hour SCr was 61.90 μmol/L, the sensitivity was 90.6%, the specificity was 95.0%, and the accuracy was 95.7%. Conclusion Urine NGAL and KIM-1 can be used as biomarkers for early diagnosis of AKI after CPB for the non-cyanotic CHD in children.
7.Study on the Chemical Constituents of Arundina graminifolia
Yupeng LI ; Ruixuan WENG ; Yongsheng TAO ; Shuang LI ; Juan WANG ; Rong HUANG ; Xiaoling WEN ; Guihua ZHANG
Journal of Kunming Medical University 2016;37(11):5-7
Objective To study the chemical constituents from the flowers of Arundina graminifolia and to find its bioactive compounds.Methods The compounds were extracted by 95% alcohol and isolated by column chromatography on silica gel and Sephadex LH-20.The structures were identified by spectroscopic analysis (1H NMR,13CNMR and EIMS).Results Eight compounds were obtained and identified as (1) 7-hydroxy-2,4-dimethoxy-9,10-dihydrophenanthrene;(2)coelonin;(3)4,7-dihydroxy-2-methoxy-9,10-dihydro-phenanthrene;(4)ephemeranthoquinone;(5)densiflorol B;(6)4-(3-hydroxyphenyl)-2-butanone;(7) stigmasterol,(8) β-sitosterol.Conclusion Among them,compound 6 is discovered for the first time from the plant.
8.Storage effect and transplant outcomes of University of Wisconsin preservation solution and histidine-tryptophan-ketoglutarate preservation solution on liver allografts: a Meta-analysis
Apaer SHADIKE ; Tuxun TUERHONGJIANG ; Yupeng LI ; Aierken AMINA ; Tao LI ; Jinming ZHAO ; Hao WEN
Chinese Journal of Digestive Surgery 2016;15(5):482-489
Objective To systematically evaluate the storage effect and transplant outcomes of University of Wisconsin (UW) preservation solution and histidine-tryptophan-ketoglutarate (HTK) preservation solution on liver allografts.Methods Literatures were researched using PubMed,Embase (1980-),Ovid Medline (1948-),The Cochrane Library,Wanfang database,VIP database from the database establishement to October 2015 with the key words including organ preservation,storage solutions,Histidine-tryptophan-ketoglutarate or HTK,custodial,bretschneider,University of Wisconsin,UW solution,viaspan,cardiosol,belzer solution,hepatic transplantation,liver transplantation,viscera transplantation,liver grafts,hepatic grafts,liver allografts,hepatic allografts,器官移植,器官保存液,UW,HTK,肝移植and比较.Two reviewers independently screened literatures,extracted data and assessed the risk of bias.All the patients using UW and HTK preservation solutions were respectively allocated into the UW group and HTK group.Count data were represented as the odds ratio (OR) and measurement data were represented as the standardized mean difference (SMD) and 95% confidence interval (CI).The heterogeneity of the studies was analyzed using the I2 test.Results Eleven literatures were retrieved,and the total sample size were 34 475 patients including 25 248 in the UW group and 9 227 in the HTK group.The results of Meta analysis showed that there were no statistically significant differences in the primary transplants nonfunction,retransplant rate and 1-year grafts overall survival rate between the 2 groups (OR =1.18,0.84,0.97,1.02,95% CI:0.55-2.57,0.47-1.50,0.66-1.42,0.66-1.58,P >0.05).There were also no statistically significant differences in the levels of alanine transaminase (ALT),aspartate transaminase (AST),total bilirubin (TBil) at postoperative day 1 between the 2 groups (SMD =-0.19,-O.30,0.30,95% CI:-0.62-0.23,-0.70-0.10,-0.01-0.61,P >0.05).There were no statistically significant differences in the postoperative prothrombin time(PT) and alkaline phosphatase(ALP) between the 2 groups (P >0.05) and in the incidence of postoperative biliary complications between the 2 groups (OR =1.49,95% CI:0.97-2.30,P > 0.05).Conclusion There is similar storage effect between UW and HTK preservation solutions on liver allografts,and no difference in the transplant outcomes.
9.Risk factors for acute kidney injury after cardiopulmonary bypass operation in children with non cyanotic congenital heart disease
Yupeng WEN ; Cheng CHANG ; Zhonglun WANG ; Jie ZHENG
Tianjin Medical Journal 2015;43(5):515-517
Objective To investigate the incidence and risk factors of acute kidney injury (AKI) after cardiopulmonary bypass(CRB) in children with non cyanotic congenital heart disease. Methods A total of 150 children who underwent cardiopulmonary bypass operation from 2012 May to 2014 May were analyzed retrospectively. The patients were divided into two groups:AKI group (n=29) and non AKI group (n=121). Clinical data were collected and compared between two groups, including gender, age and baseline serum creatinine level. Multivariate Logistic regression analysis was used to evaluate the risk factors for AKI after operation. Results There was no death in the 150 cases. Comparison between groups, there were significant differences in age, history of heart failure and (or)pneumonia, baseline serum creatinine level, baseline uric acid, body mass, CPB) time, aortic clamping time, mechanical ventilation time, postoperative transfusion and hypotension. Multivariate Logistic regression analysis showed that age (≤1 years old), the history of pneumonia and (or) heart failure, CPB time (>40 min), aortic clamping time (>30 min) were the independent risk factors for AKI after operation. Conclusion It is important to choose the best age for surgery in children, actively prevent preoperative complications and shorten the CPB and aorta blocking time for preventing the occurrence of AKI.
10.Exploration and Practice in Bilingual Teaching of Medical Organic Chemistry Experiment
Yupeng LI ; Zhong ZHANG ; Xian LI ; Min LUO ; Xiaoling WEN ; Ying LIU
Journal of Kunming Medical University 2013;(11):125-127,132
Objective Research the bilingual teaching of medical organic chemistry experiment. Methods PBL teaching method was used in bilingual teaching of medical organic chemistry experiment. Results As a result, we improved the effect of bilingual teaching in medical organic chemistry experiment. Conclusion Teaching research found that the teaching mode with a problem-centered and students-orientation approach has improved students' analysis and problem solving skills. During the process of teaching, the students have enhanced their enthusiasm of study.

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