Nuevos avances en la terapia de la insuficiencia cardiaca

Las enfermedades del corazón son un tema tratado frecuentemente en las investigaciones médicas, debido a que repercuten ampliamente en el funcionamiento del cuerpo humano. Por lo anterior, se destaca el estudio del tratamiento de las afecciones de este órgano, lo que resulta en una importante tarea para mantener y potenciar los conocimientos sobre los adelantos terapéuticos de las enfermedades relacionadas con el mismo. Se realiza este trabajo con el objetivo de describir los avances en la terapia de la insuficiencia cardiaca. Para ello se realizó una revisión de publicaciones científicas de los últimos dos años. A pesar de que existen diferencias respecto a la terapia propuesta para la insuficiencia cardiaca, las asociaciones americanas y europea de cardiología establecen firmemente la terapia cuádruple (con los inhibidores del receptor de la angiotensina neprilysin, los ß-bloqueadores, los antagonistas de receptor de los mineralocorticoides y los inhibidores del cotransportador-2 de glucosa/sodio) -dirigida a la insuficiencia cardiaca con fracción de eyección reducida-, la recomendación del dinitrato de isosorbide/hidralazina para los pacientes de raza negra, y la utilización de la cardioversión implantable en la prevención de muerte súbita. Se concluye que la armonización de estas guías, en ambos continentes, proporciona un tratamiento único para la insuficiencia cardiaca, aunque necesita un estudio adicional en los pacientes con fracción de eyección del ventrículo izquierdo normal.

Heart diseases are a topic frequently treated in medical researches, due to their wide repercussion on the functioning of the human body; therefore, the study of the treatment of these organ affections is highlighted, being an important task to maintain and enhance knowledge about therapeutic advances in diseases related to it. This work is carried out with the aim of describing the advances in heart failure therapy. A review of the scientific publications of the last two years was performed. Although there are differences regarding the proposed therapy for heart failure, the American and European Associations of cardiology firmly establish the quadruple therapy (with angiotensin receptor inhibitors neprilysin, ß-blockers; mineralocorticoids antagonist receptors and glucose/sodium cotransporters-2 inhibitors-targeted at heart failure with reduced ejection fraction-, the recommendation of isosorbide dinitrate/hydralazine for black patients, and the use of implantable cardioversion in the prevention of the sudden death. It is concluded that the harmonization of these guidelines, in both continents, provides a unique treatment for heart failure, although it needs additional study in patients with normal left ventricular ejection fraction.

El difícil camino de los péptidos natriuréticos en la insuficiencia cardiaca

Esta es una revisión sobre el papel de los péptidos natriuréticos y los intentos de utilizarlos como diana terapéutica a medida que se iba comprendiendo mejor su papel en la fisiopatología de la insuficiencia cardíaca con función sistólica deprimida. Se hace un recuento de su participación en sucesivos estudios fallidos y se explican los motivos de sus fracasos, hasta lograr el éxito deseado con la combinación del sacubitrilo/valsartan, lo que produjo un cambio de paradigma en el manejo de la insuficiencia cardíaca.

This review is conducted on the role of natriuretic peptides and the attempts to use them as a treatment as their role in the pathophysiology of heart failure with depressed systolic function was better understood. A recount of their participation in successive failed studies is provided, explaining the reasons for their failures, until achieving the desired success with the combination of sacubitril/valsartan. This produced a paradigm shift in the management of heart failure.

Angiotensin receptor-neprilysin inhibitors and cardiac remodeling

The aim of this study was to determine how sacubitril/valsartan compared with valsartan in an outpatient setting affects left ventricular remodeling in heart failure with reduced ejection fraction and functional (or secondary) mitral regurgitation (SMR) due to the effect of dual inhibition of the renin-angiotensin system and neprilysin. The outpatient study included 90 patients with chronic SMR who were followed up for 12 months. They received sacubitril/valsartan or valsartan instead of the more commonly used angiotensin-converting enzyme inhibitor enalapril for heart failure, in addition to standard medical therapy for heart failure. The difference in NT-proBNP change between groups was the primary endpoint. Changes in effective regurgitation orifice area, left ventricular ejection fraction, left ventricular end-systolic and end-diastolic volume indices, left atrial volume index, E/e' index, and exercise tolerance on the 6-minute walk test were secondary endpoints. In the treatment efficacy analysis, NT-proBNP levels decreased significantly by 37% in the sacubitril/valsartan group and by 11% in the valsartan group (P<0.001). Ejection fraction and exercise tolerance (increase in walking distance in the 6-min test) increased in the sacubitril/valsartan group (P<0.05). Also, in this group, the effective area of the regurgitation orifice, the left atrial volume index, the E/e' index, and the indices of the end-systolic and end-diastolic volume of the left ventricle (P<0.05) decreased more pronouncedly. Compared with valsartan, treatment with sacubitril/valsartan led to a significant improvement in cardiac remodeling in patients with SMR and heart failure with reduced ejection fraction.

Effects of Sacubitril Valsartan Sodium on Short-term Prognosis of Patients with Acute Anterior Myocardial Infarction Complicated with Acute Cardiac Insufficiency / 中国药房

OBJECTIVE：To investigate the effec ts of angiotensin receptor neprilysin inhibitor （ARNI）sacubitril valsartan sodium（SVS）on the short-term prognosis of patients with acute anterior myocardial infarction （AAMI）complicated with acute cardiac insufficiency. METHODS ：A total of 80 patients with AAMI and Killip grade Ⅱ-Ⅳ of cardiac function ，who met the inclusion criteria ，were randomly divided into ARNI group and control group ，with 40 patients in each group. Both groups were given the same basic standardized drug treatment ，vital signs support treatment and percutaneous coronary intervention treatment at the same time. On this basis ，ARNI group was given SVS tablet orally ，with initial dose of 25 mg each time ，twice a day ； thereafter，gradually adjust the dose to 200 mg each time ，twice a day. Control group was given Enalapril maleate tablets orally ， with an initial dose of 5 mg each time ，twice a day ；thereafter，gradually adjust the dose to 10 mg each time ，twice a day. Both groups took medicine for a long time ，and were followed up after 1，3 and 6 months of medication to the clinic. The levels of N-terminal pro-B-type natriuretic peptide （NT-proBNP）， soluble growth stimulation expressed gene 2 protein （sST2） and echocardiography indexes were compared between 2 groups before and after medication. The 6-minute walking test （6MWT）and the incidence of cardiogenic readmission events were recorded in 2 groups after medication. RESULTS ：Compared with before treatment，the indexes of the two groups were significantly improved at 1，3 and 6 months after treatment （P＜0.05）. Compared with control group ，the levels of NT-proBNP and sST 2 in ARNI group decreased significantly （P＜0.05），the levels of left ventricular ejection fraction and 6MWT increased significantly（P＜0.05），and the left ventricular end systolic diameter and left ventricular end diastolic diameter decreased significantly，after 3 and 6 months of treatm ent（P＜0.05）. However ，there was no significant difference in the velocity ratio of peak E to peak A ，pulmonary artery pressure ，right ventricular end diastolic diameter and the incidence of cardiogenic readmission events between 2 groups（P＞0.05）. CONCLUSIONS ：For patients with AAMI complicated with acute cardiac insufficiency ， compared with enalapril ，SVS can significantly improve the cardiac function （especially the left ventricular systolic function ）， reduce the inflammatory reaction of cardiomyocytes ，protect cardiomyocytes ，so as to improve the short-term prognosis of patients.

Clinical efficacy and safety of angiotensin receptor neprilysin inhibitor and angiotensin converting enzyme inhibitor in elderly patients with ischemic cardiomyopathy / 中国医师进修杂志

Objective@#To investigate the influence of angiotensinreceptor neprilysin inhibitor(ARNI) and angiotensin converting enzyme inhibitor (ACEI) on clinical efficacy and safety of elderly patients with ischemic cardiomyopathy.@*Methods@#From January 2017 to December 2018, 120 elderly patients with ischemic cardiomyopathy in the Third People′s Hospital of Cixi were divided into 2 groups according to treatment methods, 59 patients treated with ACEI (control group) and 61 patients treated with ARNI (observation group) on the basis of conventional intervention. The levels of blood lipid index, blood pressure index, B-type brain natriuretic peptide (BNP), 6- minute walking test (6MWT) and echocardiographic index, endothelium-dependent diastolic function of brachial artery (FMD) and carotid intima-media thickness (CIMT) before and after treatment were compared. The adverse reactions incidence of 2 groups were compared.@*Results@#The levels of blood lipid index and blood pressure index after treatment of 2 groups were significantly lower than those before treatment, and the differences had statistical significant (P<0.05). There were no significant differences in the levels of blood lipid index and blood pressure index after treatment between 2 groups (P>0.05). After treatment of 12 weeks, the levels of BNP, 6MWT, left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension(LVEDD) of observation group were significantly better than those of control group [(103.50 ± 23.95) ng/L vs. (175.20 ± 37.24) ng/L, (493.47 ± 92.54) m vs. (411.42 ± 61.09) m, (44.95 ± 5.89)% vs. (41.54 ± 4.21)%, (149.59 ± 33.26) mm vs. (143.24 ± 34.25) mm](P<0.05). The level of brachial artery FMD after treatment of observation group was significantly higher than that of control group [(15.14 ± 2.52)% vs. (9.25 ± 1.12)%](P<0.05). The level of CIMT after treatment of observation group was significantly lower than that of control group [(1.01 ± 0.28) mm vs. (1.32 ± 0.25) mm](P<0.05). There was no significant difference in the adverse reactions incidence between 2 groups (P>0.05).@*Conclusions@#ARNI in assisted treatment of elderly patients with ischemic cardiomyopathy can efficiently improve cardiac function, increase exercise endurance, enhance vasodilation function and dose not aggravate adverse drug reactions.

Effect of Sacubitril/Valsartan for alleviating chronic heart failure in elderly patients after acute myocardial infarction / 中华老年医学杂志

Objective@#To evaluate the effect of Sacubitril/Valsartan for alleviating chronic heart failure(CHF)in elderly patients after acute myocardial infarction(AMI).@*Methods@#A total of 87 elderly patients with AMI-induced CHF treated in Heze Shili Hospital from October 2017 to August 2018 were enrolled and randomly divided into the experimental group(n=42)and the control group(n=45). All patients were given standard AMI treatments, and patients in the experimental group were given Sacubitril/Valsartan(100 mg bid)while those in the control group received Valsartan(80 mg qd). After a follow-up of 12 months, levels of N-terminal pro-brain natriuretic peptide(NT-proBNP), left ventricular end-diastolic diameter(LVDd), left ventricular ejection fraction(LVEF), rates of rehospitalization for heart failure and all-cause mortality were compared between the two groups.@*Results@#Among the 87 patients, 51 patients(58.6%)were male and 36 were female, with an averageage of(67.4±4.0)years.After 12-months of treatment, patients in the experimental group were associated with significantly lower levels of LVDd[(47.86±3.86)mm vs.(50.73±4.39)mm, P<0.05]and NT-proBNP[(793.43±335.43)ng/L vs.(1 068.44±344.46)ng/L, P<0.05]and higher levels of LVEF[(53.74±4.08)% vs.(44.42±7.41)%, P<0.05]than those in the control group.Moreover, the rehospitalization rate for heart failure was markedly higher in the control group than that in the experimental group[15(33.3%)vs.5(11.9%), P<0.05], while the rate of all-cause mortality was similar between the two groups[2(4.8%)vs.3(6.7%), P=0.703].@*Conclusions@#Compared with Valsartan, Sacubitril/Valsartan can reduce the incidence of CHF after AMI, improve left ventricular function, and reduce the rehospitalization rate due to CHF in elderly patients.

Changes of serum Adropin protein and neprilysin levels in patients with type 2 diabetic retinopathy and analysis of influening factors / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To observe the changes of serum Adropin protein(AD)and neprilysin(NEP)levels in patients with diabetic retinopathy and to analyse the influencing factors. <p>METHODS: A total of 167 patients with type 2 diabetes were enrolled in this study. They were divided into simple type 2 diabetes group(DM group)with 59 cases and type 2 diabetic retinopathy group(DR group)with 108 cases. Furthermore, the DR group included patients in two periods of non-proliferation diabetic retinopathy(NPDR group)and proliferative diabetic retinopathy(PDR group). There were 45 patients in NPDR group and 63 patients in PDR group, meanwhile, another 57 healthy subjects were selected as the normal control group(NC group). Measuring the hight and weight and calculating body mass index(BMI). Indices of fasting plasma glucose(FPG), systolic blood pressure(SBP), diastolic blood pressure(DBP), total cholesterol(TC), triacylglycerol(TG), alanine aminotransferase(ALT), aspartate aminotransferase(AST)hemoglobin Alc(HbA1c)were be detected, while levels of serum adropin protein(AD)and neprilysin(NEP)were measured by enzyme-linked immunosorbent assay(ELISA). The correlation between AD, NEP and other indicators was analyzed by Pearson correlation analysis. The independent influence factors of both were analyzed by multiple linear regression. <p>RESULTS: Compared with the NC group, the AD level in the DM group, NPDR group, and PDR group decreased gradually, with the lowest level in the PDR group(<i>P</i><0.05). The level of NEP in each group gradually increased, and the highest one was in the PDR group(<i>P</i><0.05). Multiple linear regression analysis indicated that FPG, HbA1c and NEP were independently correlated with AD. BMI, FPG, HbA1c and AD were independently correlated with NEP.<p>CONCLUSION: In patients with diabetic retinopathy, AD level would be decreased with the progression of DR, and NEP level would be gradually increased, both of which may be involved in the development of DR.

Effect of Sacubitril/Valsartan for alleviating chronic heart failure in elderly patients after acute myocardial infarction / 中华老年医学杂志

Objective To evaluate the effect of Sacubitril/Valsartan for alleviating chronic heart failure(CHF)in elderly patients after acute myocardial infarction(AMI).Methods A total of 87 elderly patients with AMI-induced CHF treated in Heze Shili Hospital from October 2017 to August 2018 were enrolled and randomly divided into the experimental group(n=42)and the control group(n =45).All patients were given standard AMI treatments,and patients in the experimental group were given Sacubitril/Valsartan (100 mg bid)while those in the control group received Valsartan (80 mg qd).After a follow-up of 12 months,levels of N-terminal pro-brain natriuretic peptide(NT-proBNP),left ventricular end-diastolic diameter(LVDd),left ventricular ejection fraction(LVEF),rates of rehospitalization for heart failure and all-cause mortality were compared between the two groups.Results Among the 87 patients,51 patients(58.6％)were male and 36 were female,with an averageage of(67.4 ± 4.0) years.After 12-months of treatment,patients in the experimental group were associated with significantly lower levels of LVDd[(47.86±3.86)mm vs.(50.73±4.39)mm,P＜0.05]and NT-proBNP [(793.43 ± 335.43) ng/L vs.(1 068.44 ± 344.46) ng/L,P ＜ 0.05] and higher levels of LVEF[(53.74 ± 4.08) ％ vs.(44.42 ± 7.41) ％,P ＜ 0.05] than those in the control group.Moreover,the rehospitalization rate for heart failure was markedly higher in the control group than that in the experimental group[15(33.3％)vs.5(11.9％),P＜0.05],while the rate of all-cause mortality was similar between the two groups[2 (4.8％)vs.3(6.7％),P =0.703].Conclusions Compared with Valsartan,Sacubitril/Valsartan can reduce the incidence of CHF after AMI,improve left ventricular function,and reduce the rehospitalization rate due to CHF in elderly patients.

Clinical efficacy and safety of angiotensin receptor neprilysin inhibitor and angiotensin converting enzyme inhibitor in elderly patients with ischemic cardiomyopathy / 中国医师进修杂志

Objective To investigate the influence of angiotensinreceptor neprilysin inhibitor (ARNI) and angiotensin converting enzyme inhibitor (ACEI) on clinical efficacy and safety of elderly patients with ischemic cardiomyopathy.Methods From January 2017 to December 2018,120 elderly patients with ischemic cardiomyopathy in the Third People's Hospital of Cixi were divided into 2 groups according to treatment methods,59 patients treated with ACEI (control group) and 61 patients treated with ARNI (observation group) on the basis of conventional intervention.The levels of blood lipid index,blood pressure index,B-type brain natriuretic peptide (BNP),6-minute walking test (6MWT) and echocardiographic index,endothelium-dependent diastolic function of brachial artery (FMD) and carotid intima-media thickness (CIMT) before and after treatment were compared.The adverse reactions incidence of 2 groups were compared.Results The levels of blood lipid index and blood pressure index after treatment of 2 groups were significantly lower than those before treatment,and the differences had statistical significant (P ＜ 0.05).There were no significant differences in the levels of blood lipid index and blood pressure index after treatment between 2 groups (P ＞ 0.05).After treatment of 12 weeks,the levels of BNP,6MWT,left ventricular ejection fraction (LVEF),left ventricular end-diastolic dimension (LVEDD) of observation group were significantly better than those of control group [(103.50 ± 23.95) ng/L vs.(175.20 ± 37.24) ng/L,(493.47 ± 92.54) m vs.(411.42 ± 61.09) m,(44.95 ± 5.89)％ vs.(41.54 ± 4.21)％,(149.59 ± 33.26) mm vs.(143.24 ± 34.25) mm](P ＜ 0.05).The level of brachial artery FMD after treatment of observation group was significantly higher than that of control group [(15.14 ± 2.52)％ vs.(9.25 ± 1.12)％](P ＜ 0.05).The level of CIMT after treatment of observation group was significantly lower than that of control group [(1.01 ± 0.28) mm vs.(1.32 ± 0.25) mm] (P＜ 0.05).There was no significant difference in the adverse reactions incidence between 2 groups (P＞ 0.05).Conclusions ARNI in assisted treatment of elderly patients with ischemic cardiomyopathy can efficiently improve cardiac function,increase exercise endurance,enhance vasodilation function and dose not aggravate adverse drug reactions.

Effect of Hei Xiaoyaosan on Expressions of Aβ1-42, GSK-3β, NEP, IDE in Hippocampus Area of Alzheimer's Dementia Mice / 中国实验方剂学杂志

Objective: To observe the effect of Hei Xiaoyaosan on expressions of β-amyloid 1-42 peptide(Aβ1-42),glycogen synthase kinase-3β(GSK-3β),neprilysin(NEP),insulin-degrading enzyme(IDE) in the hippocampus area of Alzheimer's dementia mice. Method: After weighing, 42 APP/PSI bivalent transgenic mice were randomly divided into 4 groups:10 mice in the model group, 10 mice in the positive drug control group, 11 mice in the high-dose Hei Xiaoyaosan group, and 11 mice in the low-dose Hei Xiaoyaosan group; 10 wild C57BL/6J mice of the same age and strain were used for negative control group. Drugs were administered to mice by gavage once a day for 12 weeks. Then the behavior of all the mice were detected by Morris water maze, the morphological changes in hippocampal neurons were observed by hematoxylineosin(HE) staining, the expressions of Aβ1-42, GSK-3β, NEP and IDE proteins in hippocampus were detected by immunohistochemistry. Result: After 3 months of treatment, compared with negative control groups, the average escaping latency periods prolonged significantly, and the number of cross-platform was decreased significantly in model group (Pβ1-42 and GSK-3β proteins in model mice hippocampus were significantly increased (PPPβ1-42 and GSK-3β proteins in the hippocampus of drug groups were significantly decreased (PPPConclusion: Hei Xiaoyaosan can significantly improve the learning and memory abilities of AD mice, which may be related to the reduction of cognitive impairment in AD mice by regulating abnormal deposition and degradating Aβ in the hippocampus.

Research progress of LCZ696 in patients with chronic heart failure / 中国综合临床

Chronic heart failure(CHF)is the performance of end-stage cardiovascular disease and the leading cause of death in recent years.With the rapid development of medical care,the mortality rate of heart failure is still high.This is one in the two major challenges in the cardiovascular field in the 21st century.The new drug LCZ696 is a dual inhibitors of angiotensin receptor blockers(ARB)and neprilysin(NEP),which may lead to new hope for patients with heart failure.In order to determine the efficacy and safety of LCZ696 in the treatment of heart failure,foreign countries have carried out some large-scale trials,such as PARAMOUT, PARADIGM,TITRATION and so on.The results of these studies reflected the superiority of LCZ696 compared with enalapril,valsartan and other drugs in the treatment of chronic heart failure.ARB/antiotensin converting enzyme inhibitors(ACEI)targets the angiotensin receptor to dilate blood vessels and inhibits the sympathetic nerve,but their effects on sodium withdrawal and diuresis are weak.The sacubitril in LCZ696 prevents natriuretic peptide from degrading,strengthens the natriuretic diuretic and further expansion of blood vessels.Thereby it improves water and sodium retention and cardiac function.It can play a better synergistic role combined with valsartan.

Effect of Electroacupuncture on Levels of β-amyloid and Neprilysin Proteins in the Cerebral Cortex of Alzheimer's Disease Mice Based on "Mutual Assistance of Kidney and Brain" Theory / 针刺研究

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the levels of Aβ 1-40 and Aβ 1-42 and neprilysin (NEP) protein in the temporal cortex of SAMP 8 mice with Alzheimer's disease (AD), so as to explore its mechanism underlying improvement of AD based on the theory of "mutual assistance of kidney and brain" in traditional Chinese medicine. METHODS: Eighteen male SAMP 8 mice were randomly assigned to 3 groups: model, EA and medication (memantine, n＝6/group), and 6 male homologous SAMR 1 mice were used as the normal control group. According to the "mutual assistance of kidney and brain" theory, EA (2 Hz，0.6 mA) was applied at "Baihui"(GV 20), bilateral "Shenshu"(BL 23) and "Taixi"(KI 3) for 15 min, once daily for 8 consecutive weeks. Mice of the medication group were treated with intragastric administration of memantine (20 mg•kg－1•d－1) for 8 weeks. The contents of Aβ 1-40 and Aβ 1-42 in the temporal cortex were assayed using ELISA, and the expression of NEP protein in the temporal cortex was detected using immunohistochemistry and Western blot (WB), separately. RESULTS: The contents of Aβ 1-40 and Aβ 1-42 were significantly higher in the model group than in the control group (P0.05). Immunohistochemistry stain showed that NEP-positive products mainly expressed in the perikaryon of neurons of the temporal cortex. CONCLUSION: EA intervention based on "mutual assistance of kidney and brain" theory has a good efficacy in up-regulating NEP expression and down-regulating Aβ 1-40 and Aβ 1-42 levels in the temporal cortex of AD mice, suggesting a potential effectiveness in the prevention and treatment of AD.

Re-understand the clinical significance of natriuretic peptide family / 中华检验医学杂志

Although BNP/NT-proBNP has been widely accepted as the gold standard biomarker for the diagnosis and prognosis of heart failure, and current guidelines on heart failure list the application of natriuretic peptide in the diagnosis and prognosis of heart failure as ⅠA recommendations, the latest studies discovered a lot of new finding, which show that some of our thoughts on the test result of BNP/NT-proBNP is wrong. It is important for clinical and laboratory physicians to understand the latest progress on natriuretic peptide family. It will help them use BNP/NT-proBNP more properly. In the future, as the new drugs, which work via natriuretic peptide family, will be used widely in patients, the test of natriuretic peptide family will become more important.

Clinical features and prognosis in CD10- pre-B acute lymphoblastic leukemia / 中华血液学杂志

Objective@#To analyze the clinical features and prognosis of acute lymphoblastic leukemia patients with immunophenotype of CD10-pre-B (CD10- pre B-ALL) .@*Methods@#6 adult cases with CD10- pre B-ALL immunophenotypes were analyzed retrospectively, related literatures were reviewed to clarify these kind of patients’ clinical features and prognosis.@*Results@#CD10- pre B-ALL occurred in 1.5% of ALL, 1.8% of B-ALL and 11.5% of pre B-ALL respectively. All the 6 patients were male with the median age as 33.5 years old, the median white blood cells was 101.78×109/L, MLL-AF4 fusion transcripts were evident in all cases. Complete remission (CR) was achieved in 5 patients after first induction chemotherapy, 1 patient failed to respond to induction therapy, and got CR after 3 courses of chemotherapy. 2 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in CR1, 1 patient relapsed in the short term and underwent allo-HSCT in CR2. 1 patient was still waiting for allo-HSCT. Of the 2 patients who didn’t receive transplantation, 1 died following a relapse, the other remained to be in CR.@*Conclusions@#CD10- pre B-ALL was a rare but distinct subtype in adult ALL characterized by male dominance, high onset white blood cells and MLL rearrangement rate. Conventional chemotherapy produced a high response rate but more likely relapse, allo-HSCT may have the potential to improve the prognosis of these patients.

Identification of neprilysin as a potential target of arteannuin using computational drug repositioning

ABSTRACT The discovery of arteannuin (qinghaosu) in the 20th Century was a major advance for medicine. Besides functioning as a malaria therapy, arteannuin is a pharmacological agent in a range of other diseases, but its mechanism of action remains obscure. In this study, the reverse docking server PharmMapper was used to identify potential targets of arteannuin. The results were checked using the chemical-protein interactome servers DRAR-CPI and DDI-CPI, and verified by AutoDock Vina. The results showed that neprilysin (also known as CD10), a common acute lymphoblastic leukaemia antigen, was the top disease-related target of arteannuin. The chemical-protein interactome and docking results agreed with those of PharmMapper, further implicating neprilysin as a potential target. Although experimental verification is required, this study provides guidance for future pharmacological investigations into novel clinical applications for arteannuin.

Current Drug Therapy in Chronic Heart Failure: the New Guidelines of the European Society of Cardiology (ESC)

Congestive heart failure (HF) is a morbidity that is increasing worldwide due to the aging population and improvement in (acute) care for patients with cardiovascular diseases. The prognosis for patients with HF is very poor without treatment. Furthermore, (repeated) hospitalizations for cardiac decompensation cause an increasing economic burden. Modern drugs and the consequent implementation of therapeutic recommendations have substantially improved the morbidity and mortality of HF patients. This paper provides an overview of the current pharmacological management of HF patients, based on the 2016 guidelines of the European Society of Cardiology (ESC).

Overview on an Originate AngiotensinⅡReceptor-Neprilysin Inhibitor with Double Effect:Sacubitril/Val-sartan / 中国药师

An originate angiotensin Ⅱreceptor-neprilysin inhibitor sacubitril/valsartan with double effect and a new active mode can not only promote the protection of heart and neuroendocrine system , but also inhibit renin-angiotensin-aldosterone system .Sacubi-tril/valsartan is the first and only one conformed by clinical trials with better efficacy when compared with standard therapy drug enala -pril, and its safety is higher as well .Sacubitril-valsartan represents a promising new treatment option for heart failure patients with low-ered risk of cardiovascular death and hospitalization for heart failure .

The efficiency of expressing human neprilysin by using lentiviral vector transduction in neural stem cells / 中华神经科杂志

Objective To study the transduction efficiency of expressing human neprilysin by using a lentiviral vector (Lenti-NEP) in mouse embryonic neural stem cells (NSC) in vitro.Methods Primary NSC were harvested from C57BL/6J pregnant mouse at embryonic day 11.5 and transducted with LentiNEP.Immunofluorescent stainingand Western blot were performed to detect NEP protein expression in NSC.Degradation of amyloid beta 1-40 (Aβ1-40) by NEP protein transduced with Lenti-NEP in NSC was analyzed using ELISA and HPLC.Results Over 90％ NSC were successfully transduced with Lenti-NEP via observation of fused protein green fluorescent protein under the microscopy.Expressions of NEP transduced with Lenti-NEP in NSC and of the markers of NSC (nestin) and neuron (MAP2).The enzyme activity of 2.5 μg (21.00 ± 2.51) and 1.0 μg (15.00 ± 0.54) NEP on degrading Aβ1-40 was shown to improve significantly compared to 0.5 μg NEP(8.00 ±0.81,t =40.4 and 12.7,respectively,both P ＜0.01).The activity of NEP was inhibited in the presence of 50 μmol/L phosphoramidon (0.5 pg:0.08 ±0.01 ;1.0 μg:0.04 ±0.01 ;2.5 μg:0.05 ±0.01,t =17.2,51.3 and 14.1,respectively,all P ＜0.01).The hydrolytic cleavage on degrading Aβ1-40 by NEP was 11.4％,28.4％ and 93.7％ with incubation for 1 h,4 h and 12 h,respectively.Conclusions Lentiviral vector successfully delivers NEP gene to NSC in vitro.Targeting on NEP and NSC may provide potential therapeutic tool for Alzheimer' s disease.