1.Changes of miR-30a-5p during the pathogenesis of acute myocardial infarction and its potential molecular mechanisms
Guoxin LIANG ; Chang GUO ; Hongyue TANG ; Mingming ZHANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(4):567-574
Objective To evaluate the potential of miR-30a-5p as a novel indicator of acute myocardial infarction(AMI)and the underlying molecular mechanisms.Methods AMI-associated microRNAs(miRNAs)and mRNA microarray datasets were downloaded from the GEO database.Real-time fluorescence quantitative PCR(qRT-PCR)technique was used to detect the level of miRNAs in serum samples;automatic biochemistry was used to detect other biochemical indicators.Receiver operating characteristic(ROC)curve analysis and Spearson correlation analysis were performed to assess the value of miR-30a-5p as a diagnostic AMI marker.The target genes of miR-30a-5p were predicted with the R language multiMiR package,and the protein interaction network was constructed by the STRING database.The results were imported into Cytoscape 3.7.1 software to screen the pivotal genes of the network.The R language clusterProfiler package performed KEGG and GO analyses on the hub genes to explore the clinical significance of miR-30a-5p in AMI and its potential molecular mechanisms.Results Compared with the control group,miR-30a-5p was upregulated significantly in the serum of patients in the AMI group(P<0.05);miR-30a-5p was positively correlated with the levels of CK-MB,CK,TnT,proBNP and CRP(rs=0.489,P<0.001;rs=0.347,P<0.001;rs=0.545,P<0.001;rs=0.533,P<0.001;rs=0.206,P<0.05).The area under the ROC curve was 0.862,with sensitivity of 84.4%and specificity of 74.2%.A total of 780 differentially expressed genes(DEGs)were obtained from the two datasets.A total of 1 061 target genes of miR-30a-5p and 61 common genes were identified by taking the intersection set.Among the central genes of PPI,BCL6,FOSL2,JDP2,LYN,PDE4D,SOCS3 and SOX4 scored high and were closely associated with the occurrence of AMI.KEGG and GO enrichment analyses showed that miR-30a-5p might regulate JAK-STAT,NF-kappaB and Wnt signaling pathways,which were involved in inflammatory response,apoptosis,autophagy and post-infarction remodeling,and thus participated in the process of AMI.Conclusion Serum miR-30a-5p is up-regulated in the early stage of AMI,and the study on miR-30a-5p and its regulatory pathways can help with the diagnosis and treatment of myocardial infarction.
2.Model construction and effects of combined diagnosis of peripheral blood miR-202-5p and interleukin-6 in acute myocardial infarction
Chang GUO ; Guoxin LIANG ; Hongyue TANG ; Xin LIU ; Mingming ZHANG
Clinical Medicine of China 2024;40(5):345-351
Objective:Construct a combined detection model of miR-202-5p and interleukin-6 (IL-6) and explore its diagnostic value for acute myocardial infarction (AMI).Methods:Clinical data of 202 patients with coronary atherosclerotic heart disease (CHD) who were admitted to the Department of Cardiology and Emergency Department of Hebei People's Hospital from August 2020 to August 2022 were retrospectively analyzed, including 106 AMI patients and 96 non AMI patients. The clinical characteristics and blood levels of miR-202-5p and IL-6 were compared between the two groups, T-test was used for inter group comparison of measurement data that conforms to normal distribution, non parametric rank sum test was used for inter group comparison of measurement data that does not conform to normal distribution, and χ2 test was used for inter group comparison of count data. Binary Logistic regression model was used to determine the independent influencing factors of AMI, and a combined diagnostic model was constructed according to the analysis results, the diagnostic efficacy of miR-202-5p, IL-6 and combined detection for AMI was evaluated by ROC curve, and the clinical diagnostic effect was observed. Results:The expression levels of serum total cholesterol (4.40 (3.71, 5.00) mmol/L), low density lipoprotein cholesterol (2.99 (2.39,3.47) mmol/L), lipoprotein a (276.80 (182.58,390.13) mg/L), interleukin-4(IL-4)(2.69(2.29,3.16) μg/L), IL-6(89.82(68.26,107.16) μg/L) in AMI group were significantly higher than those of non-AMI group (4.04 (3.12, 4.73) mmol/L, 2.75 (2.15, 3.21) mmol/L, 213.45 (146.73, 348.80) mg/L, 2.46 (1.92, 3.01)] μg/L, 45.89 (32.38, 62.83) μg/L, while miR-202-5p(0.33 (0.27,0.38)) was lower than that in the non-AMI group (0.51 (0.36,0.68)), ( H values were 4 167.50, 4 234.00, 4 262.50, 4 228.00, 1 513.00, and 2 098.50, respectively; P values were 0.027, 0.040, 0.047, 0.038, <0.001, <0.001, respectively). Multivariate binary logistic regression analysis showed that high levels of IL-6 and low levels of miR-202-5p were independent risk factors for AMI. The joint diagnostic model of IL-6 and miR-202-5p was Logit (P)=-1.046-5.236 × miR-202-5p+0.051 × IL-6, with probability value P as the diagnostic indicator and P=0.45 as the diagnostic threshold. ROC curve results showed that the area under curve (AUC) of IL-6 and miR-202-5p were 0.851 and 0.794, respectively, while the AUC of the combined diagnosis model was 0.894, indicating that the diagnosis accuracy was higher than that of a single index. Compared with isolated detection, the sensitivity, specificity and Kappa value of the IL-6+miR-202-5p collaborative test for AMI prediction were increased, especially the diagnosis results were close to a high degree of agreement with the actual results ( Kappa=0.732). Conclusion:High levels of IL-6 and low levels of miR-202-5p are independent influencing factors for AMI, and the combined diagnosis model of the two has clinical application value.
3.MiR-224-5p overexpression inhibits oxidative stress by regulating the PI3K/Akt/FoxO1 axis to attenuate hypoxia/reoxygenation-induced cardiomyocyte injury
Guoxin LIANG ; Hongyue TANG ; Chang GUO ; Mingming ZHANG
Journal of Southern Medical University 2024;44(6):1173-1181
Objectives To investigate the regulatory role of miRNA-224-5p in hypoxia/reoxygenation(H/R)-induced H9c2 cardiomyocyte injury.Methods Plasma samples were collected from 160 patients with acute myocardial infarction and 80 healthy controls(HC)to measure miRNA-224-5p levels and other biochemical parameters.In cultured H9c2 cells with H/R injury,the effects of transfection with miR-224-5p mimics or a negative control sequence on cell viability,malondialdehyde(MDA)content,and superoxide dismutase 2(SOD2)and lactate dehydrogenase(LDH)activities were tested.Dual luciferase reporter gene assay was performed to verify the targeting relationship between miR-224-5p and PTEN.Bioinformatics methods were used to analyze the potential mechanisms of the target genes.The expression of miRNA-224-5p in the treated cells was detected with qRT-PCR,the protein expressions of PTEN,Bcl-2,Bax,cleaved caspase-3,SOD2,p-PI3K/PI3K,p-Akt/Ak and p-FoxO1/FoxO1 were determined using Western blotting,and cell apoptosis was analysed with flow cytometry.Results The levels of blood glucose,C-reactive protein,CK,CK-MB and cTnI were significantly higher in the AMI group compared with the HC group(P<0.05).The expression level of miR-224-5p was significantly lowered in patients with STEMI and NSTEMI and in H9c2 cells with H/R injury.The viability of H9c2 cells decreased time-dependently following H/R injury.PTEN was a target gene of miR-224-5p,and the PI3K/Akt pathway was the most significantly enriched pathway.H9c2 cells with H/R injury showed significantly decreased SOD2 activity,increased LDH activity and MDA content,increased cell apoptosis,decreased protein expression levels of p-PI3K,p-Akt,p-FoxO1,SOD2,and Bcl-2,and increased expressions of PTEN,Bax,and cleaved caspase-3.These changes were obviously attenuated by trasnfection of the cells with miR-224-5p mimics prior to H/R exposure.Conclusion MiR-224-5p overexpression upregulates the expression of the antioxidant gene SOD2 through the PI3K/Akt/FoxO1 axis to relieve H/R-induced oxidative stress and reduce apoptosis of H9c2 cells.
4.MiR-224-5p overexpression inhibits oxidative stress by regulating the PI3K/Akt/FoxO1 axis to attenuate hypoxia/reoxygenation-induced cardiomyocyte injury
Guoxin LIANG ; Hongyue TANG ; Chang GUO ; Mingming ZHANG
Journal of Southern Medical University 2024;44(6):1173-1181
Objectives To investigate the regulatory role of miRNA-224-5p in hypoxia/reoxygenation(H/R)-induced H9c2 cardiomyocyte injury.Methods Plasma samples were collected from 160 patients with acute myocardial infarction and 80 healthy controls(HC)to measure miRNA-224-5p levels and other biochemical parameters.In cultured H9c2 cells with H/R injury,the effects of transfection with miR-224-5p mimics or a negative control sequence on cell viability,malondialdehyde(MDA)content,and superoxide dismutase 2(SOD2)and lactate dehydrogenase(LDH)activities were tested.Dual luciferase reporter gene assay was performed to verify the targeting relationship between miR-224-5p and PTEN.Bioinformatics methods were used to analyze the potential mechanisms of the target genes.The expression of miRNA-224-5p in the treated cells was detected with qRT-PCR,the protein expressions of PTEN,Bcl-2,Bax,cleaved caspase-3,SOD2,p-PI3K/PI3K,p-Akt/Ak and p-FoxO1/FoxO1 were determined using Western blotting,and cell apoptosis was analysed with flow cytometry.Results The levels of blood glucose,C-reactive protein,CK,CK-MB and cTnI were significantly higher in the AMI group compared with the HC group(P<0.05).The expression level of miR-224-5p was significantly lowered in patients with STEMI and NSTEMI and in H9c2 cells with H/R injury.The viability of H9c2 cells decreased time-dependently following H/R injury.PTEN was a target gene of miR-224-5p,and the PI3K/Akt pathway was the most significantly enriched pathway.H9c2 cells with H/R injury showed significantly decreased SOD2 activity,increased LDH activity and MDA content,increased cell apoptosis,decreased protein expression levels of p-PI3K,p-Akt,p-FoxO1,SOD2,and Bcl-2,and increased expressions of PTEN,Bax,and cleaved caspase-3.These changes were obviously attenuated by trasnfection of the cells with miR-224-5p mimics prior to H/R exposure.Conclusion MiR-224-5p overexpression upregulates the expression of the antioxidant gene SOD2 through the PI3K/Akt/FoxO1 axis to relieve H/R-induced oxidative stress and reduce apoptosis of H9c2 cells.
5.Honokiol alleviated neurodegeneration by reducing oxidative stress and improving mitochondrial function in mutant SOD1 cellular and mouse models of amyotrophic lateral sclerosis.
Yujun ZHOU ; Jingshu TANG ; Jiaqi LAN ; Yong ZHANG ; Hongyue WANG ; Qiuyu CHEN ; Yuying KANG ; Yang SUN ; Xinhong FENG ; Lei WU ; Hongtao JIN ; Shizhong CHEN ; Ying PENG
Acta Pharmaceutica Sinica B 2023;13(2):577-597
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting both upper and lower motor neurons (MNs) with large unmet medical needs. Multiple pathological mechanisms are considered to contribute to the progression of ALS, including neuronal oxidative stress and mitochondrial dysfunction. Honokiol (HNK) has been reported to exert therapeutic effects in several neurologic disease models including ischemia stroke, Alzheimer's disease and Parkinson's disease. Here we found that honokiol also exhibited protective effects in ALS disease models both in vitro and in vivo. Honokiol improved the viability of NSC-34 motor neuron-like cells that expressed the mutant G93A SOD1 proteins (SOD1-G93A cells for short). Mechanistical studies revealed that honokiol alleviated cellular oxidative stress by enhancing glutathione (GSH) synthesis and activating the nuclear factor erythroid 2-related factor 2 (NRF2)-antioxidant response element (ARE) pathway. Also, honokiol improved both mitochondrial function and morphology via fine-tuning mitochondrial dynamics in SOD1-G93A cells. Importantly, honokiol extended the lifespan of the SOD1-G93A transgenic mice and improved the motor function. The improvement of antioxidant capacity and mitochondrial function was further confirmed in the spinal cord and gastrocnemius muscle in mice. Overall, honokiol showed promising preclinical potential as a multiple target drug for ALS treatment.
6.Progress on the correlation between peripheral blood inflammatory index and the prognosis of pancreatic cancer
Hongyue YANG ; Yanzhang TIAN ; Shaojian MO ; Lingbo HUO ; Haowen TANG
Chinese Journal of Hepatobiliary Surgery 2022;28(4):310-313
Globally, the incidence of pancreatic cancer is on a rise. Pancreatic cancer is characterized by difficulty in early diagnosis, frequent distant metastasis, low surgical resection rate, and high risk of postoperative recurrence. Better treatments need to be developed to prolong the prognosis. Studies have confirmed that inflammation is closely correlated with tumorigenesis, and inflammatory mediators play important roles on tumor microenvironment of pancreatic cancer and lead to poor prognosis. This article reviewed the progress on the correlation between peripheral blood inflammatory index and the prognosis of pancreatic cancer.
7.Comparative Study of Cytotoxicity and Anti-inflammatory Effects between Raw Aconitium kusnezoffii and Aconitium kusnezoffii Processed with Terminalia chebula
Meiru ZHI ; Shu HAN ; Kaiyang LIU ; Xitao HAN ; Yanan TANG ; Ziqin LIU ; Hongyue WANG ; Fei LI ; Hong DU
China Pharmacy 2020;31(22):2701-2705
OBJECTIVE:To comp are cytotoxicity and anti-inflammatory effects of raw Aconitium kusnezoffii and A. kusnezoffii processed with Terminalia chebula . METHODS :Using H 9c2 cardiomyocytes isolated from rat as subjects ,CCK-8 assay was used to detect the effects of 0.5,1,2,4,6,8,10 mg/mL raw A. kusnezoffii and A. kusnezoffii processed with T. chebula on cell inhibition rate after cultured for 4,8,12,24 h. Hoechst 33258 staining was used to observe the effects on cell morphology characteristics after treated with 2,4,6 mg/mL raw A. kusnezoffii and A. kusnezoffii processed with T. chebula . Using macrophages RAW264.7 cells as subjects ,CCK-8 assay was used to detect the effects of 0.05,0.1,0.25,0.5,0.75,1,1.5,2 mg/mL raw A. kusnezoffii and A. kusnezoffii processed with T. chebula on cell survival rate after cultured for 24 h. ELISA assay was used to detect the effects of 0.05,0.1,0.25,0.5 mg/mL raw A. kusnezoffii and A. kusnezoffii processed with T. chebula on the release of NO , TNF-α and IL-6 in RAW 264.7 inflammation cells induced by LPS. RESULTS :When the mass concentration was 0.5,1 mg/mL, neither raw A. kusnezoffii and A. kusnezoffii processed with T. chebula had no inhibitory effect on H 9c2 cells. When the mass concentration was 2 mg/mL,the inhibitory effects of A. kusnezoffii processed with T. chebula on H 9c2 cells was higher than that of raw A. kusnezoffii (P<0.05 or P<0.01);fluorescence intensity of cells treated for 24 h was stronger than that of raw A. kusnezoffii,but its nucleus was intact. When the mass concentration was 4-10 mg/mL,the inhibitory rate of A. kusnezoffii processed with T. chebula on H 9c2 cells at different time points (except for 24 h culture of 8,10 mg/mL)was significantly lower than raw A. kusnezoffii (P<0.05 or P<0.01). The characteristics of cell morphology also showed that the fluorescence intensity of raw A. kusnezoffii group at 4,6 mg/mL was stronger than that of A. kusnezoffii processed with T. chebula group,and the cell nucleus fragmentation was more serious in the raw A. kusnezoffii group. 0.05-0.5 mg/mL raw A. kusnezoffii and A. kusnezoffii processed with T. chebula had no toxicity to RAW264.7 cells. 0.25,0.5 mg/mL raw A. kusnezoffii and 0.1,0.25,0.5 mg/mL A. kusnezoffii processed with T. chebula showed significant inhibitory effect on the release of NO ,0.05,0.1,0.25,0.5 mg/mL raw A. kusnezoffii and A. kusnezoffii processed with T. chebula showed significant inhibitory effect on the release of TNF-α and IL-6 in RAW 264.7 cell(P<0.05 or P< 0.01). The inhibitory effects of A. kusnezoffii processed with T. chebula at the same concentration on the release of NO was better than that of raw A. kusnezoffii ,but poorer than raw A. kusnezoffii in the inhibitory effects on the release of TNF-α and IL-6. CONCLUSIONS:The toxicity of A. kusnezoffii can be reduced after processed with T. chebula ,especially the toxicity of it in medium or high concentration and short-term use is lower than that of raw A. kusnezoffii . At the same time ,the anti-inflammatory effect of A. kusnezoffii processed with T. chebula is comparable to that of raw A. kusnezoffii at the same concentration.
8.The value of contrast-enhanced ultrasound and contrast-enhanced CT in the differential diagnosis of benign and malignant gallbladder diseases
Chunlin TANG ; Yanli GUO ; Ping CHEN ; Kaixuan CHEN ; Ying TAN ; Zhaohui CHEN ; Yan WANG ; Qiangwei LIU ; Ye ZOU ; Hongyue ZENG
Chinese Journal of Medical Ultrasound (Electronic Edition) 2018;15(4):251-257
Objective To comparatively analyze the image characteristic of contrast-enhanced ultrasound(CEUS)and contrast-enhanced computed tomography(CECT),and explore the diagnostic value of the two methods in benign and malignant lesions of gallbladder.Methods comparative analysis the image characteristic of CEUS and CECT,the preoperative diagnostic results of 86 cases of gallbladder diseases were confirmed by pathology.Results The enhancement patterns of CEUS and CECT in benign and malignant lesions of gallbladder are similar.The sensitivity,specificity and accuracy of CEUS were 77.9%(53/68),77.8%(14/18),77.9%(67/86),respectively.The sensitivity,specificity and accuracy of CECT were 75%(51/68),55.6%(10/18),70.9%(61/86),respectively.The sensitivity,specificity and accuracy of the combination of CEUS and CECT were 83.8%(57/68),55.6%(10/18),77.9%(67/86),respectively.The accuracy of the combination of CEUS and CECT was higher than that of CECT in the diagnosis of malignant gallbladder lesions [(53.9±10.00)s vs(35.50±6.72)s],the differences were statistically significant(t=6.729,P<0.001).Conclusions The enhancement patterns of CEUS and CECT in benign and malignant gallbladder lesions are similar.The combination of CEUS and CECT is helpful for improving the diagnostic accuracy of malignant gallbladder lesions.CEUS and CECT could corroborate and complement each other,and provide more valuable information for the differential diagnosis of benign and malignant gallbladder lesions.
9. Clinical features and surgical treatment effect of patients with cardiac cavernous hemangioma
Qiulan YANG ; Bing TANG ; Xiaohui ZHOU ; Jianpeng WANG ; Hongyue WANG ; Shuiyun WANG
Chinese Journal of Cardiology 2017;45(9):786-790
Objective:
To investigate the clinical features and surgical treatment effect of patients with cardiac cavernous hemangioma.
Methods:
Clinical data of 9 patients (5 male, aged from 4 to 53 years old) with cardiac cavernous hemangioma, who underwent surgical treatment from November 2002 to March 2015 and the diagnosis of cardiac cavernous hemangioma was confirmed by postoperative histological examination, were retrospectively analyzed. Effects of surgical treatment were analyzed.
Results:
Four patients were asymptomatic (heart murmur presented in 3 patients during physical examination). Three patients presented with palpitation, chest distress, and short of breath. One patient presented with epigastric discomfort and another patient presented with intermittent fever for more than 10 months. ST and T wave changes of electrocardiogram were found in 2 patients, cardiac mass was detected in the right heart chamber in 5 patients by echocardiography, and no cardiac mass was detected the rest 4 patients. Cardiac masses were resected en bloc, then the adjacent tissues were repaired in 7 patients, and mass was partially resected due to the involvement with adjacent heart structure. No cardiac mass was found during operation in 1 case, impaired mitral valve structure was excised and postoperative pathologically confirmed as cardiac valve cavernous angioma on the excised mitral valve structure. No signs of recurrence or enlargement of cardiac cavernous hemangioma were found during the 11(10, 11)years follow up.
Conclusions
There is no specific clinical feature for patients with cardiac cavernous hemangioma. It is difficult to detect the cardiac valve cavernous angioma by echocardiography before surgery. Individualized surgical treatment is associated with good clinical outcome in this patient cohort. However, the clinical features and surgical treatment effect of patients with cardiac cavernous hemangioma still need to investigate in large sample trial.
10.Research progress of chronic disease management in community
Yulu XIE ; Wenxi SUN ; Yinghui JIN ; Hongyue WEI ; Qi TANG
Chinese Journal of Practical Nursing 2016;32(7):549-552
The aging of population and the increasingly morbidity rate of chronic disease had brought great influence on public health and economy.And community whose scientific management model could improve effectivity was a main prevention place for chronic disease.Thus on the basis of domestic and foreign literatures,several types of chronic disease community management models were introduced,and aimed at providing a reference for community chronic disease management.

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