1.Effects of trimetazidine on cardiomyocyte apoptosis in late reperfusion after acute myocardial infarction in canine
Mingwei XIA ; Likun MA ; Hua YU ; Kefu FENG
Chinese Pharmacological Bulletin 1986;0(05):-
Aim To investigate the cardioprotective effects and the possible mechanism of trimetazidine in the risky areas during late reperfusion after acute myocardial infarction in canine.Methods Twenty-four adult dogs were randomized into three groups:sham operation group(n=8),late reperfusion group(LR,n=8),late reperfusion after trimetazidine treatment group(LR+TMZ,n=8).Physiological saline was orally given in the sham operation group and LR group and trimetazidine(2 mg?kg-1?d-1) in the LR+TMZ group for fourteen days.After that later,all chests were opened and coronary areteries were exposed.Exceptly shame operation group,the late reperfusion of acute myocardial infarction model was made by ligating the coronary for 10 h,followed by reperfusion of 10 h.Apoptotic index were detected by TUNEL.The Bcl-2,Bax,Cytochrome C and apoptosis-inducing factor(AIF) proteins were detected by immunohistochemistry.Results Compared with those of LR group,myocardial apoptotic index and the expression of Bax,Cytochrome C and AIF proteins in LR+TMZ decreased significantly(all P
2.Protective effect and the possible mechanism of Nano-Se on myocardium of experimental diabetes mice
Hongwu CHEN ; Likun MA ; Hua YU ; Kefu FENG
Chinese Journal of Pathophysiology 1989;0(05):-
AIM:To observe the protective effect of Nano-Se on myocardium of experimental diabetes mice.METHODS:Sixty healthy male KM mice were chosen,ten of which were selected randomly as the normal control group.After fasted for 24 h,the rest 50 mice were injected with streptozotocin(STZ,50 mg/kg)intraperitoneally for 5 d.At 7th d,the blood-sugar was measured from vena caudalis,40 mice,of which blood-sugar exceeded 16.65mmol/L,were selected and randomized into 4 groups:the positive control group,low dose(25 ?g/kg)Nano-Se group,mid dose(50 ?g/kg)Nano-Se group,high dose(50 ?g/kg)Nano-Se group.All mice were given intragastric administration of 0.2 mL normal saline and corresponding dose of Nano-Se.The body weights were measured every week,and the dose of which was adjusted according to the change of the body weights.8 weeks later,the mice were killed and cardiac muscle of the left ventricle was taken.The myocardium was prepared to 10% homogenate for measuring SOD,GSH-Px activity and MDA content.The myocardial cell apoptosis was measured by TUNEL.The expressions of Bc1-2 and Bax proteins were determined by immunohistochemistry.RESULTS:Compared to normal group,the SOD and GSH-Px activities in positive control group decreased,MDA level increased,the rate of myocardial cell apoptosis increased significantly,Bc1-2 protein expression deceased and Bax protein expression increased.Compared to positive control group,the SOD and GSH-Px activities in low and mid dose Nano-Se groups expression increased,MDA level decreased,myocardial cell apoptosis rate decreased,Bc1-2 protein expression increased and Bax protein expression decreased.Moreover,the SOD and GSH-Px activities in high dose Nano-Se group decreased obviously compared to those in mid dose Nano-Se group.MDA level and myocardial cell apoptosis rate increased,Bc1-2 protein expression decreased and Bax protein expression increased,no significant difference in SOD,GSH-Px activity,MDA level and myocardial cell apoptosis rate was observed compared with positive control group.CONCLUSION:The damage of cardiac muscle is alleviated when a certain dose of Nano-Se is supplied to diabetes mice.The protective mechanism may be related to antioxidation,blood-sugar adjustment and the increase of Bc1-2 expressing.
3.Exploration into quantitative MR diagnostic criteria of subacromial impingement syndrome
Jinghua CHEN ; Kefu LIU ; Jing FENG ; Hongtao YU ; Jing ZHANG ; Jian XIAO
Journal of Practical Radiology 2018;34(5):744-748
Objective To investigate the relationships of MR indexes such as acromio humeral intervals (AHI),lateral extension of the acromion (LEA) and inclination angle of the acromion with the subacromial impingement syndrome (SIS).Methods 151 patients underwent MRI examination of shoulder joints,they were grouped according to age,gender and location of acromion.The differences in age,gender and MR indexes were compared between SIS group and non SIS group.The distribution statuses of SIS in different groups were compared at the same time,the relationships of various MR indexes with SIS were investigated and analyzed.Results There were no statistical differences in age,location distribution,the average shortest AHI value and the thickness of the subacromial bursal effusion between SIS group and non SIS group (P > 0.05).There showed statistical difference in gender between the two groups (P =0.000),and there were more males than females in both groups.The acromion exactly covered the supraspinatus tendon in 79 patients,the average value of LEA in the SIS group was greater than that in the non SIS group,and there showed statistically significant difference between the two groups (P =0.002),the Youden index of LEA was 0.40,the sensitivity was 61% and the specificity was 79%.The inclination angle of the acromion in the SIS group was smaller than that in the non SIS group,and there was a statistically significant difference between the two groups (P =0.019),the Youden index of the inclination angle of the acromion was 0.18,the sensitivity was 62% and the specificity was 56%.47 patients in the SIS group had subacromial bursal effusion,51 patients in the non SIS group had subacromial bursal effusion.The thickness of the subacromial bursal effusion in the SIS group was greater than the non SIS group,and there showed statistically significant difference between the two groups (P =0.002),the Youden index of the thickness of the subacromial bursal effusion was 0.34,the sensitivity was 78 % and the specificity was 56 %.Conclusion LEA,the inclination angle of the acromion and the thickness of the subacromial bursal effusion can be used as quantitative MR diagnostic criteria of SIS.The LEA measured by cardiothoracic ratio is simple and easy to use.
4.Correlation Between Cutaneous Adverse Reactions Caused by Aromatic Antiepileptic Drugs and Human Leukocyte Antigen Gene Polymorphism
Jiping HUO ; Jingchen TIAN ; Zhigang ZHAO ; Shenghui MEI ; Xingang LI ; Kefu YU
Herald of Medicine 2018;37(2):206-211
Aromatic antiepileptic drugs such as carbamazepine are the first-line treatment for epilepsy. The adverse reactions have greatly limited their clinical application. The occurrence rate of severe skin adverse reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) is low,but they are often fatal.Human leukocyte antigen (HLA) gene polymorphisms are reported to be related with skin adverse reactions caused by aromatic antiepileptic drugs,but the exact mechanism is unclear.This article will perform a review about the correlation between skin adverse reactions caused by aromatic antiepileptic drugs and HLA gene polymorphisms published in recent years,in order to provide theoretical basis for further study of HLA susceptibility genes in Chinese Han population,and provide a reference for achieving individualized treatment of epilepsy.
5.Research on Effect of CD47 on Immune Microenvironment and Immunotherapy of Lung Squamous Cell Carcinoma Based on Bioinformatics Database
SHI Weizhong ; XU Bei ; HAN Rong ; ZHAO Zhigang ; YU Kefu
Chinese Journal of Modern Applied Pharmacy 2023;40(17):2372-2377
OBJECTIVE To investigate the effect of gene CD47 on immune microenvironment of lung squamous cell carcinoma and predict its immune response. METHODS The differences in the expression of CD47 between lung squamous cell carcinoma tissues and normal tissues were compared through The Cancer Genome Atlas(TCGA) databases. CD47 involved immune-related pathways were analyzed by Gene Set Enrichment Analysis(GSEA). Tumor Immune Estimation Resource(TIMER) databases and TISIDB databases(http://cis.hku.hk/TISIDB/TISIDB) were employed to analyze the relationship between CD47 gene expression in lung squamous cell carcinoma and immune cells infiltration in the tumor microenvironment. And further explored the associations between CD47 and other immune-related molecules such as PD-1, PD-L1, CTLA-4, IDO-1. Using the pRRophetic and TIDE algorithms, this study predicted the correlation between the expression of CD47 gene and chemotherapy drug sensitivity as well as the response to immunotherapy. RESULTS Compared with normal tissues, CD47 was lower expressed in lung squamous cell carcinoma tissues. It was found that CD47 could activate immune-related pathways such as the inflammatory response, interferon alpha response, interferon gamma response and JAK-STAT pathway. In lung squamous cell carcinoma tissues, the expression level of CD47 was significantly positively correlated with the infiltration level of B-cells, CD8T-cells, CD4T-cells, macrophage, neutrophils and dendritic cells according to the two databases. At the same time, CD47 showed a positive correlation with other immune checkpoints such as PD-1, PD-L1, CTLA-4, IDO1. The result of chemotherapy sensitivity indicated that in lung squamous cell carcinoma tissues, IC50 values of high expression CD47 group were lower than that for chemotherapy drugs such as sunitinib, dasatinib, doxorubicin and gemcitabine. However, the response rate to immunotherapy was lower in the low expression group for the immunotherapy. CONCLUSION CD47 is low expressed in lung squamous tissue, it can activate immune related pathways, and has a high response rate to immunotherapy. It can be used as a novel molecular marker for lung squamous cell carcinoma.
6. Pinocembrin Promotes OPC Differentiation and Remyelination via the mTOR Signaling Pathway
Qi SHAO ; Ming ZHAO ; Wenwen PEI ; Yingyan PU ; Mingdong LIU ; Weili LIU ; Zhongwang YU ; Kefu CHEN ; Hong LIU ; Li CAO ; Ming ZHAO ; Benqiang DENG ; Ming ZHAO ; Kefu CHEN
Neuroscience Bulletin 2021;37(9):1314-1324
The exacerbation of progressive multiple sclerosis (MS) is closely associated with obstruction of the differentiation of oligodendrocyte progenitor cells (OPCs). To discover novel therapeutic compounds for enhancing remyelination by endogenous OPCs, we screened for myelin basic protein expression using cultured rat OPCs and a library of small-molecule compounds. One of the most effective drugs was pinocembrin, which remarkably promoted OPC differentiation and maturation without affecting cell proliferation and survival. Based on these in vitro effects, we further assessed the therapeutic effects of pinocembrin in animal models of demyelinating diseases. We demonstrated that pinocembrin significantly ameliorated the progression of experimental autoimmune encephalomyelitis (EAE) and enhanced the repair of demyelination in lysolectin-induced lesions. Further studies indicated that pinocembrin increased the phosphorylation level of mammalian target of rapamycin (mTOR). Taken together, our results demonstrated that pinocembrin promotes OPC differentiation and remyelination through the phosphorylated mTOR pathway, and suggest a novel therapeutic prospect for this natural flavonoid product in treating demyelinating diseases.
7.Pinocembrin Promotes OPC Differentiation and Remyelination via the mTOR Signaling Pathway.
Qi SHAO ; Ming ZHAO ; Wenwen PEI ; Yingyan PU ; Mingdong LIU ; Weili LIU ; Zhongwang YU ; Kefu CHEN ; Hong LIU ; Benqiang DENG ; Li CAO
Neuroscience Bulletin 2021;37(9):1314-1324
The exacerbation of progressive multiple sclerosis (MS) is closely associated with obstruction of the differentiation of oligodendrocyte progenitor cells (OPCs). To discover novel therapeutic compounds for enhancing remyelination by endogenous OPCs, we screened for myelin basic protein expression using cultured rat OPCs and a library of small-molecule compounds. One of the most effective drugs was pinocembrin, which remarkably promoted OPC differentiation and maturation without affecting cell proliferation and survival. Based on these in vitro effects, we further assessed the therapeutic effects of pinocembrin in animal models of demyelinating diseases. We demonstrated that pinocembrin significantly ameliorated the progression of experimental autoimmune encephalomyelitis (EAE) and enhanced the repair of demyelination in lysolectin-induced lesions. Further studies indicated that pinocembrin increased the phosphorylation level of mammalian target of rapamycin (mTOR). Taken together, our results demonstrated that pinocembrin promotes OPC differentiation and remyelination through the phosphorylated mTOR pathway, and suggest a novel therapeutic prospect for this natural flavonoid product in treating demyelinating diseases.
Animals
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Cell Differentiation
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Flavanones
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Mice
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Mice, Inbred C57BL
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Myelin Sheath/metabolism*
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Oligodendroglia/metabolism*
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Rats
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Remyelination
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Signal Transduction
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TOR Serine-Threonine Kinases/metabolism*