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【Objective】 To investigate the effects of formononetin (FMN) on cardiomyocyte apoptosis and HSP90/AKT in rats with dilated cardiomyopathy-mediated heart failure. 【Methods】 Echocardiography, ELISA, histological staining, and TUNEL staining were used to observe the protective effect of different doses of FMN on dilated cardiomyopathy-mediated heart failure in rats and the apoptosis of cardiomyocytes. The potential targets of formononetin on dilated cardiomyopathy-mediated heart failure were obtained from TCMSP, DisGeNet, GeneCards, and other databases, the key targets were obtained according to the protein-protein interaction (PPI) network, and the key targets were verified by molecular docking. Western blotting was used to further verify the regulatory role of key targets in the treatment of dilated cardiomyopathy-mediated heart failure with formononetin. 【Results】 Formononetin could reduce the levels of LVIDS, LVIDD, NT-pro BNP, cTn-T, CK, CK-MB, and LDH in rats with dilated cardiomyopathy-mediated heart failure, increase the levels of EF and FS, and reduce the apoptosis of cardiomyocytes. FMN had a strong binding effect on 10 key targets (AKT1, HSP90AA1, CASP3, MAPK1, MMP9, SRC, ALB, HRAS, IGF1, and EGFR) screened by network pharmacology, with HSP90AA1 and AKT1 having the strongest binding effect. Formononetin decreased the expression of HSP90, AKT and downstream CASP3 protein, but increased the expression of p-AKT in myocardial tissue. 【Conclusion】 Formononetin may inhibit the expression of HSP90, promote phosphorylation of AKT to p-AKT, and inhibit the expression of CASP3, thereby reducing the apoptosis of cardiomyocytes and improving myocardial tissue damage, so as to achieve the purpose of treating dilated cardiomyopathy-mediated heart failure.
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In this research,a new phospholipid based monolith was fabricated by in situ co-polymerization of 1-dodecanoyl-2-(11-methacrylamidoundecanoyl)-sn-glycero-3-phosphoethanolamine and ethylene dimethacrylate to mimick bio-membrane environment.Excellent physicochemical properties of this novel monolith that were achieved included column efficiency,stability,and permeability.Moreover,the biomimetic monolith showed outstanding separation capability for a series of intact proteins and small molecules.In particular,it exhibited good potential as an alternative to the commercial immobilized artificial membrane(IAM)column(IAM.PC.DD2)for studying drug-membrane interactions.This study not only enriched the types of IAM stationary phases,but also provided a simple model for the prediction of phosphatidylethanolamine related properties of drug candidates.
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OBJECTIVE To prepare Gambogic acid （GA） nanocapsules （GA-LNCs） and Neogambogic acid （NGA） nanocapsules（NGA-LNCs），and to evaluate their antidiabetic activities. METHODS Using water as the aqueous phase ，medium- chain triglyceride as the oil phase and polyethylene glycol monostearate as the surfactant ，GA-LNCs and NGA-LNCs were prepared by phase inversion method. Using entrapment efficiency and drug-loading amount as index ，the formulation technologies of above 2 nanocapsules were optimized by simplex lattice design. Its physical and chemical properties were investigated. The diabetic mice model was established. GA-LNCs and NGA-LNCs （1.92 and 2.42 mg/kg respectively ）were given intragastrically ，once a day ，for consecutive 6 weeks. The fasting blood glucose of mice ，the activities of superoxide dismutase （SOD）and glutathione peroxidase （GSH-Px），the contents of malondialdehyde （MDA），total cholesterol （TC），triglyceride （TG），high-density lipoprotein cholesterol（HDL-C）and low-density lipoprotein cholesterol （LDL-C）were all detected. RESULTS The optimal formulation of 2 kinds of nanocapsules included 60％ water，10％ medium-chain triglyceride ，30％ polyethylene glycol monostearate （total amount of the three was 2 g）and 35 mg GA or NGA . The encapsulation efficiencies of GA-LNCs and NGA-LNC obtained by the optimal formulation were （92.01±0.68）％ and（93.12±2.11）％；the drug-loading amount were （0.99±0.21）％ and（1.21±0.22）％， respectively. GA-LNCs and NGA-LNCs were yellow ，homogeneous and transparent liquid without precipitation. They were spherical in microscopic shape ， and had obvious shell- Δ 基金项目：吉林省科技发展计划项目（No.20200404090YY）；吉 membrane structure. The particle sizes were （28.11 ± 9.76） 林省教育厅科学技术研究项目（No.JJKH20210372KJ） ＊硕士研究生 。研究方向 ：植物药 。E-mail：zhanhe0108@163. and（22.06±6.84）nm；Zeta potential were （－4.09±1.00） com and（－17.40±1.32）mV，and polydispersity were 0.93±0.06 # 通信作者：讲师，博士。研究方向：中药有效成分治疗疾病的作 and 0.74±0.12. The results of animal experiments showed that 用机制。E-mail：chenweijia_jlau@163.com both GA-LNCs and NGA-LNCs could sig nificantly increase 中国药房 2022年第33卷第9期 China Pharmacy 2022Vol. 33 No. 9 ·1075· the activities of SOD and GSH-Px and the seru m content of HDL-C （P＜0.05 or P＜0.01）in model mice ，and significantly decreased the fasting blood glucose and the serum contents of MDA ， TC， TG and LDL-C （P＜0.05 or P＜0.01）. CONCLUSIONS GA-LNCs，NGA-LNCs prepared in this study are good in physical and chemical properties and have good anti-diabetes activity.
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Objective@#To investigate the incremental value of coronary flow reserve (CFR) assessed by cadmium zinc telluride(CZT)-SPECT as an adjunct to myocardial perfusion imaging (MPI) in the diagnosis of coronary artery disease (CAD).@*Methods@#Data of 132 patients (89 males, 43 females; 40-81 years) with or suspected with CAD who successfully underwent rest and stress MPI and CFR from November 2017 to October 2018 in Zhongshan Hospital Affiliated to Fudan University were retrospectively analyzed. Based on coronary angiography (CAG) as the " gold standard" , the value of MPI and MPI+ CFR in the diagnosis of CAD was evaluated and compared. χ2 test or Fisher exact probability test was used for data analysis.@*Results@#Of 132 patients, 61 (46.2%) were CAD with stenosis of at least 75% in one vessel (47.5%, 29/61), two vessels (34.4%, 21/61), or three vessels (18.0%, 11/61). A total of 104 (26.3%) vessels with stenosis of at least 75%, 25 (6.3%) vessels with stenosis of 65%-74%, and 30 (7.6%) vessels with stenosis of 50%-64% were found in 396 vessels. For detecting coronary stenosis of at least 75%, the sensitivity and accuracy of MPI on per-patient analysis were 86.89%(53/61) and 68.94%(91/132), which increased to 96.72%(59/61; χ2=3.921, P<0.05) and 87.88%(116/132; χ2=13.984, P<0.01) by MPI+ CFR. On per-vessel analysis, the sensitivity and accuracy of MPI were 72.12%(75/104) and 77.53%(307/396) and increased to 96.15%(100/104; χ2=22.511, P<0.01) and 85.10%(337/396; χ2=7.479, P<0.05) by MPI+ CFR. The sensitivity of MPI for predicting one, two, and three vessels disease were 72.41%(21/29), 42.86%(9/21), and 5/11 and were improved to 93.10%(27/29; χ2=4.350, P=0.037), 90.48%(19/21; χ2=10.714, P=0.001), and 11/11 (P=0.012) by MPI+ CFR. For coronary with stenosis of 65%-74%, the sensitivity of MPI was 24.00%(6/25) and was improved to 64.00%(16/25; χ2=8.117, P=0.004) by MPI+ CFR. For coronary with stenosis of 50%-64%, the sensitivity of MPI was 40.00%(12/30) and was improved to 76.67%(23/30; χ2=8.297, P=0.004) by MPI+ CFR.@*Conclusion@#As an adjunct to MPI, CFR can significantly improve the sensitivity and accuracy in the diagnosis of CAD, particularly for patients with mild stenosis and multivessel CAD.
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Objective To investigate the incremental value of coronary flow reserve ( CFR) as-sessed by cadmium zinc telluride(CZT)-SPECT as an adjunct to myocardial perfusion imaging (MPI) in the diagnosis of coronary artery disease (CAD). Methods Data of 132 patients (89 males, 43 females; 40-81 years) with or suspected with CAD who successfully underwent rest and stress MPI and CFR from November 2017 to October 2018 in Zhongshan Hospital Affiliated to Fudan University were retrospectively analyzed. Based on coronary angiography (CAG) as the " gold standard" , the value of MPI and MPI+CFR in the di-agnosis of CAD was evaluated and compared. χ2 test or Fisher exact probability test was used for data analy-sis. Results Of 132 patients, 61 (46.2％) were CAD with stenosis of at least 75％ in one vessel (47.5％, 29/ 61), two vessels (34.4％, 21/ 61), or three vessels (18.0％, 11/ 61). A total of 104 (26.3％) vessels with stenosis of at least 75％, 25 (6.3％) vessels with stenosis of 65％-74％, and 30 (7.6％) vessels with stenosis of 50％-64％ were found in 396 vessels. For detecting coronary stenosis of at least 75％, the sensi-tivity and accuracy of MPI on per-patient analysis were 86.89％(53/ 61) and 68.94％(91/ 132), which in-creased to 96.72％(59/ 61; χ2 = 3.921, P<0.05) and 87.88％(116/ 132; χ2 = 13.984, P<0.01) by MPI+CFR. On per-vessel analysis, the sensitivity and accuracy of MPI were 72.12％ (75/ 104) and 77. 53％(307/ 396) and increased to 96.15％(100/ 104; χ2 = 22. 511, P<0.01) and 85.10％(337/ 396; χ2 = 7.479, P<0.05) by MPI+CFR. The sensitivity of MPI for predicting one, two, and three vessels disease were 72. 41％(21/ 29), 42.86％ (9/ 21), and 5/ 11 and were improved to 93.10％ (27/ 29; χ2 = 4.350, P =0. 037), 90.48％(19/ 21; χ2 = 10.714, P = 0.001), and 11/ 11 (P = 0.012) by MPI+CFR. For coronary with stenosis of 65％-74％, the sensitivity of MPI was 24. 00％(6/ 25) and was improved to 64.00％(16/25; χ2 = 8.117, P= 0.004) by MPI+CFR. For coronary with stenosis of 50％-64％, the sensitivity of MPI was 40.00％(12/ 30) and was improved to 76.67％(23/ 30; χ2 = 8.297, P= 0.004) by MPI+CFR. Conclu-sion As an adjunct to MPI, CFR can significantly improve the sensitivity and accuracy in the diagnosis of CAD, particularly for patients with mild stenosis and multivessel CAD.
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Objective To observe the effect of a walking correcting tape on the kinematics and temporal-spatial indicators of gait after a stroke. Methods Thirty hemiplegic stroke survivors were randomly divided into a control group ( n=15) and a correcting tape group ( n=15) . In addition to their routine rehabilitation program, the control group received 30 minutes of walking training five times a week for 3 weeks with any necessary oral guidance and posture correction. The correcting tape group performed the same walking training assisted by a self-made walking correcting tape. Before and after the treatment, the kinematics and temporal-spatial indicators of both groups were quantified using three-dimensional gait analysis. Results After the treatment, the peak angles of hip and knee flex-ion were significantly higher in the taped group than in the control group and in the taped group before the treatment ( P≤0.05) . After the treatment, the walking speeds, stride frequencies and stride lengths of both groups were signifi-cantly better than before the treatment, but those of the former group were all significantly better than the latter ( P≤0.05 for both) . Conclusions Correcting tape can improve the peak angles of hip and knee flexion of hemiplegic legs and improve the walking capacity of stroke patients.
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Aims To investigate the protective effects of noninvasive limb ischemic preconditioning (LIPC) on myocardial ischemia-reperfusion (I /R)injury,and to explore the mechanism.Methods Healthy male Wistar rats were divided randomly into I /R,I /R +LIPC,I /R +5-Hydroxydecanoate (5-HD)and I /R +LIPC +5-HD groups.The I /R +LIPC and I /R +LIPC-5-HD groups of rats were subjected to three cy-cles of LIPC induction per day with 5 min of reperfu-sion after occlusion for 5 min at the left hind limb for 3 days.All rats were subjected to myocardial I /R injury on the fourth day.The I /R +5-HD and I /R +LIPC-5-HD groups of rats were given the inhibitor of ATP-sen-sitive potassium channel 5-HD before and during myo-cardial I /R injury. Results Compared with I /R group,LIPC reduced myocardial infarct size (P <0.05),lowered cardiocyte apoptosis index and Fas, FasL positive cell number (P <0.01 ),increased the reduced nitric oxide (NO)/endothelin (ET)-1 ratio (P <0.05)in serum in I /R +LIPC group.5-HD a-bolished the protective effects induced by LIPC in I /R+LIPC-5-HD group.Compared with normal myocardi-al tissue,expression of mir-30a-3p was increased in I /R group (P <0.01 )and was decreased in LIPC group (P <0.01 ).Conclusion LIPC alleviates myocardial I /R injury and improves endothelial function. The mechanism may be related with the opening of ATP-sensitive potassium channel,regulating the balance be-tween NO and ET-1 and decreasing the expression of myocardial mir-30a-3p.
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<p><b>OBJECTIVE</b>To explore the expression pattern of Mus81 gene in Chinese Han patients with colorectal cancer and analyze its correlation with the clinicopathological parameters and the tumor markers.</p><p><b>METHODS</b>Mus81 expression was detected using nested quantitative real-time PCR in the colorectal cancer tissues and corresponding adjacent normal tissues from 43 Chinese Han patients. The correlations of Mus81 expression profile with the clinicopathological parameters and common tumor markers were evaluated.</p><p><b>RESULTS</b>Mus81 expression level was significantly lower in the colorectal cancer tissues than in the corresponding adjacent normal tissues (114.6 ± 68.0 vs 202.5 ± 109.0, P<0.001). Of the 43 patients, 32 (74.4%) showed down-regulated Mus81 expression, which correlated significantly with distant metastasis (P=0.043), high TNM stage (P=0.022) and high P53 protein expression (P=0.011) of the tumor.</p><p><b>CONCLUSION</b>Down-regulation of Mus81 in colorectal cancer is correlated with tumor metastasis and progression, suggesting the value of Mus81 as a potential marker for colorectal cancer in Chinese Han patients.</p>
Subject(s)
Humans , Biomarkers, Tumor , Colorectal Neoplasms , Diagnosis , Genetics , DNA-Binding Proteins , Genetics , Disease Progression , Down-Regulation , Endonucleases , Genetics , Prognosis , Real-Time Polymerase Chain ReactionABSTRACT
The enzymatic synthesis of endomorphins were carried out by immobilized papain on sodium alginate-chitosan (IPSAC). The reaction has been carried out in two steps. First, Trp-Phe-NH2 was obtained by Boc-Trp-OH coupling with Phe-NH2 using IPSAC catalyst in microaqueous acetonitrile system with a 27.8 % yielding as determined by high performance liquid chromatography (HPLC). The catalytic properties of IPSAC were examined by studying the dependence of pH, ionic strength, solution content, reaction temperature,enzyme loading and reaction time over the yields. The results of orthogonal experiments indicated that pH was the most significant factor that influenced this synthesis. Second, Boc-Tyr-Pro-OMe and Trp-Phe-NH2 were suspended into the microaqueous acetonitrile to produce Tyr-Pro-Trp-Phe-NH2 (endomorphin-1) with a 35.2% yield.
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Objective:To compare microcolumn gel Coombs test and test tube Coombs test for IgG anti-A and anti-B titre in serum of pregnant women with blood type O.The critical titre for IgG anti-A and anti-B should be established in domestic microcolumn gel Coombs' test.Methods:524 blood samples of pregnant women with blood type O,whose husbands were of blood type A or B,were detected simultaneously by domestic microcolumn gel Coombs' test and test tube Coombs test.The results were analyzed using paired "t " test,"?2 " test and regression analysis.Results:IgG anti-A mean titres determined by the two methods separately were 249.98 and 120.85,and IgG anti-B mean titre were 156.98 and 76.38.IgG anti-A and anti-B titration in domestic microcolumn gel Coombs'test showed significantly higher titres(mean 2.07 fold and mean 2.06 fold) than in test tube Coombs test in all samples studied(t=19.64,P