Discovery of novel tranylcypromine-based derivatives as LSD1 inhibitors for gastric cancer treatment.

As an important epigenetic regulator, histone lysine specific demethylase 1 (LSD1) has become an attractive target for the discovery of anticancer agents. In this work, a series of tranylcypromine-based derivatives were designed and synthesized. Among them, compound 12u exhibited the most potent inhibitory potency on LSD1 (IC50 = 25.3 nM), and also displayed good antiproliferative effects on MGC-803, KYSE450 and HCT-116 cells with IC50 values of 14.3, 22.8 and 16.3 µM, respectively. Further studies revealed that compound 12u could directly act on LSD1 and inhibit LSD1 in MGC-803 cells, thereby significantly increasing the expression levels of mono-/bi-methylation of H3K4 and H3K9. In addition, compound 12u could induce apoptosis and differentiation, inhibit migration and cell stemness in MGC-803 cells. All these findings suggested that compound 12u was an active tranylcypromine-based derivative as a LSD1 inhibitor that inhibited gastric cancer.

Protective effects of Moutan Cortex polysaccharides components on renal injury in diabetic nephropathy rats / 中国中药杂志

This study investigated the protective effects of Moutan Cortex polysaccharides components(MCPC) on the renal tissues of diabetic nephropathy(DN) rats and explored their regulation effect on inflammatory response and oxidative stress. The DN rat model was induced by high-glucose and high-fat diet combined with streptozotocin(STZ), and then the rats were randomly divided into control group, model group, positive group and MCPC high(120 mg·kg~(-1)·d~(-1)), low(60 mg·kg~(-1)·d~(-1)) dose groups. After 12 weeks treatment, blood was taken from the orbit of the rats, and then they were sacrificed before the kidney tissues were collected. The serum and tissues were detected for related biochemical indicators and pathological changes of the kidney. Immunohistochemical methods were used to determine the expression of FN and ColⅣ in the kidney tissue of DN rats. Compared with the model group, blood glucose, serum creatinine, blood urea nitrogen and 24 h urine protein in the MCPC high-dose group were significantly reduced(P<0.01). The results of HE, PAS, Masson staining showed that glomerular basement membrane thickening, Bowman's capsule narrowing and inflammatory cell infiltration in DN rats were improved in the MCPC high-dose group; the activity of T-SOD and GSH-Px in serum significantly increased(P<0.001), and the expression level of FN significantly decreased(P<0.001). The high-dose MCPC treatment could effectively inhibit the abnormal expression of Col Ⅳ(P<0.001) and significantly reduce the levels of AGEs and RAGE in serum(P<0.001), the content of VCAM-1 and IL-1β in serum(P<0.001), and the levels of IL-1β mRNA in kidney tissue(P<0.001), but failed to effectively reduce VCAM-1 mRNA levels in kidney tissues. The high-dose MCPC could significantly improve pathological injury of renal tissue and related renal indicators in DN rats, and achieve renal protection in DN rats mainly by regulating oxidative stress and inflammatory factors.

Practice and development of structural characteristics and quality control of multi-dimensional structure of basic components of genuine material of Moutan Cortex / 中国中药杂志

Traditional Chinese medicine is the product of clinical medication practice of the Chinese nation for thousands of years. Its material basis is the key to reveal the essence of the roles of traditional Chinese medicine, and the fundamental guarantee to solve the difficulties in the quality control of traditional Chinese medicine. However, the material basis of traditional Chinese medicine is to exert the overall pharmacodynamic effect through multi-targets, multi-approaches and mutual cooperation, resulting in unclear quality control index. In recent years, the quality control standards of traditional Chinese medicine have experienced great changes by shifting the focus from the appearance characteristics to the internal material basis, which however is limited to the control of a single com-ponent or multiple components. In other words, the intrinsic effectiveness and safety could not be guaranteed without the characteristics of the integrity of traditional Chinese medicine. With Moutan Cortex as an example, this paper analyzed the evolution of Moutan Cortex quality standards based on Chinese Pharmacopoeia, and comprehensively summarized the material basis of Moutan Cortex. Based on the theory of "component structure", this study analyzed current quality control of the material basis of Moutan Cortex and its preparations, and expounded the development trend of multi-dimensional quality control, so as to lay a foundation for establishing a more rational quality control system for traditional Chinese medicine in the future.

Structural characteristics of pharmacodynamical components in genuine Moutan Cortex / 中国中药杂志

Guided by the theory of "component structure", we analyzed the structural characteristics of pharmacodynamical components in genuine Moutan Cortex. The compositions of organic small molecules were determined by high performance liquid chromatography(HPLC) for 20 batches of genuine Moutan Cortex and 12 batches of non-genuine Moutan Cortex. By means of similarity analysis, clustering analysis(CA), principal component analysis(PCA) and orthogonal partial least-squares discriminant analysis(OPLS-DA), the elements in structural characteristics of the pharmacodynamical components were extracted as follows: terpene glycosides components(oxidized paeoniflorin, paeoniflorin,galloyl paeoniflorin, benzoyloxy paeoniflorinand benzoyl paeoniflorin), tannin components(1,3,6-tri-O-galloside acyl glucose, pentagalloyl glucose), and phenolic acid components(methyl gallate, paeonol). The contents and quantity ratios of terpene glycoside component, tannin component and phenolic acid components in genuine Moutan Cortex were determined as 14.1, 12.5, 21.7 mg·g~(-1), 1.00∶0.89∶1.54. The contents and quantity ratios of the oxidized paeoniflorin, paeoniflorin and benzoylpaeoniflorin in the terpene glycoside components were characteristic and determined as 2.05, 7.05, 3.30 mg·g~(-1), 1.00∶3.44∶1.61. The unique structural characteristics of genuine Moutan Cortex provide scientific basis for the formulation of quality standards.

Retrospective Analysis of Risk Factors for Related Complications of Chemical Ablation on Hypertrophic Obstructive Cardiomyopathy.

BACKGROUND: The analysis of risk factors for predicting related complications has not been reported to date. OBJECTIVE: This study aims to investigate the risk factors of related complications of percutaneous transluminal septal myocardial ablation (PTSMA) for hypertrophic obstructive cardiomyopathy (HOCM) retrospectively. METHOD: Clinical data, and one-year follow-up results of patients with HOCM, who underwent PTSMA between January 2000 and July 2013 in the Department of Cardiology, Liaoning Province People's Hospital, Liaoning Province, China, were retrospectively analyzed to determine risk factors for operative complications with multiple logistic regression analysis. All p values are two-sided, with values of p < 0.05 being considered statistically significant. RESULTS: Among 319 patients with HOCM, PTSMA was performed in 224 patients (120 males and 104 females, mean age was 48.20 ± 14.34 years old). The incidence of PTSMA procedure-related complications was 36.23% (66/224), which included three cardiac deaths, two cardiac shocks, one ST-segment elevated myocardial infarction, two ventricular fibrillations, 20 third-degree atrioventricular (AV) blocks (four patients were implanted with a permanent pacemaker (PPM)), 32 complete right bundle branch blocks, two complete left bundle branch blocks, and four puncture-related complications. After multivariate logistic regression analysis, it was found that age, gender, coronary artery diseases, diabetes, heart rate, cardiac function on admission, the number of septal ablations, and the volume of alcohol were not independent risk factors correlated to the whole complications, except for hypertension (OR: 4.856; 95% CI: 1.732-13.609). Early experience appears to be associated with the occurrence of complications. CONCLUSION: Hypertension was an independent risk factor for PTSMA procedure-related complications. It might be much safer and more efficient if PTSMA procedures are restricted to experienced centers, according to the analysis results for the learning curve.

Retrospective Analysis of Risk Factors for Related Complications of Chemical Ablation on Hypertrophic Obstructive Cardiomyopathy / Análise Retrospectiva de Fatores de Risco para Complicações Relacionadas com Ablação Química na Cardiomiopatia Hipertrófica Obstrutiva

Abstract Background: The analysis of risk factors for predicting related complications has not been reported to date. Objective: This study aims to investigate the risk factors of related complications of percutaneous transluminal septal myocardial ablation (PTSMA) for hypertrophic obstructive cardiomyopathy (HOCM) retrospectively. Method: Clinical data, and one-year follow-up results of patients with HOCM, who underwent PTSMA between January 2000 and July 2013 in the Department of Cardiology, Liaoning Province People's Hospital, Liaoning Province, China, were retrospectively analyzed to determine risk factors for operative complications with multiple logistic regression analysis. All p values are two-sided, with values of p < 0.05 being considered statistically significant. Results: Among 319 patients with HOCM, PTSMA was performed in 224 patients (120 males and 104 females, mean age was 48.20 ± 14.34 years old). The incidence of PTSMA procedure-related complications was 36.23% (66/224), which included three cardiac deaths, two cardiac shocks, one ST-segment elevated myocardial infarction, two ventricular fibrillations, 20 third-degree atrioventricular (AV) blocks (four patients were implanted with a permanent pacemaker (PPM)), 32 complete right bundle branch blocks, two complete left bundle branch blocks, and four puncture-related complications. After multivariate logistic regression analysis, it was found that age, gender, coronary artery diseases, diabetes, heart rate, cardiac function on admission, the number of septal ablations, and the volume of alcohol were not independent risk factors correlated to the whole complications, except for hypertension (OR: 4.856; 95% CI: 1.732-13.609). Early experience appears to be associated with the occurrence of complications. Conclusion: Hypertension was an independent risk factor for PTSMA procedure-related complications. It might be much safer and more efficient if PTSMA procedures are restricted to experienced centers, according to the analysis results for the learning curve.

Resumo Fundamento: A análise dos fatores de risco para previsão de complicações relacionadas não foi relatada até o momento. Objetivo: Este estudo tem como objetivo investigar retrospectivamente os fatores de risco de complicações relacionadas da ablação miocárdica septal transluminal percutânea (PTSMA) para cardiomiopatia hipertrófica obstrutiva (CMHO). Método: Dados clínicos e resultados de acompanhamento de um ano de pacientes com CMHO submetidos a PTSMA entre janeiro de 2000 e julho de 2013 no Departamento de Cardiologia do Hospital Popular da Província de Liaoning, província de Liaoning, China, foram analisados retrospectivamente para determinar fatores de risco para complicações operatórias com análise de regressão logística múltipla. Todos os valores de p são bilaterais, com valores de p < 0,05 sendo considerados estatisticamente significativos. Resultados: Entre os 319 pacientes com CMHO, a PTSMA foi realizada em 224 pacientes (120 homens e 104 mulheres, com idade média de 48,20 ± 14,34 anos). A incidência de complicações relacionadas ao procedimento PTSMA foi de 36,23% (66/224), incluindo três mortes cardíacas, dois choques cardíacos, um infarto do miocárdio com supradesnivelamento de ST, duas fibrilações ventriculares e 20 bloqueios atrioventriculares (AV) de terceiro grau (quatro pacientes receberam implantes de marca-passo permanente), 32 bloqueios completos de ramo direito, dois bloqueios completos de ramo esquerdo e quatro complicações relacionadas com a punção. Após análise de regressão logística multivariada, verificou-se que idade, sexo, doenças coronarianas, diabetes, frequência cardíaca, função cardíaca à admissão, número de ablações septais e volume de álcool não foram fatores de risco independentes correlacionados com as complicações totais, exceto para hipertensão (OR: 4,856; IC 95%: 1,732-13,609). A experiência principiante parece estar associada à ocorrência de complicações. Conclusão: A hipertensão arterial foi um fator de risco independente para complicações relacionadas com o procedimento de PTSMA. Pode ser muito mais seguro e eficiente se os procedimentos de PTSMA forem restritos a centros experientes, de acordo com os resultados da análise para a curva de aprendizado.

Preliminary exploration of the measurement of walking speed for the apoplectic people based on UHF RFID.

The number of the apoplectic people is increasing while population aging is quickening its own pace. The precise measurement of walking speed is very important to the rehabilitation guidance of the apoplectic people. The precision of traditional measuring methods on speed such as stopwatch is relatively low, and high precision measurement instruments because of the high cost cannot be used widely. What's more, these methods have difficulty in measuring the walking speed of the apoplectic people accurately. UHF RFID tag has the advantages of small volume, low price, long reading distance etc, and as a wearable sensor, it is suitable to measure walking speed accurately for the apoplectic people. In order to measure the human walking speed, this paper uses four reader antennas with a certain distance to reads the signal strength of RFID tag. Because RFID tag has different RSSI (Received Signal Strength Indicator) in different distances away from the reader, researches on the changes of RSSI with time have been done by this paper to calculate walking speed. The verification results show that the precise measurement of walking speed can be realized by signal processing method with Gaussian Fitting-Kalman Filter. Depending on the variance of walking speed, doctors can predict the rehabilitation training result of the apoplectic people and give the appropriate rehabilitation guidance.

Patients with nephrolithiasis had lower fetuin-A protein level in urine and renal tissue.

Fetuin-A acts as an inhibitor of systemic and local ectopic calcification and inflammatory response, but the role of fetuin-A in the etiology of urolithiasis is still unclear. We aim to investigate the expression of fetuin-A in the serum, urine and renal tissue of patients with or without nephrolithiasis. 48 patients with nephrolithiasis (group A) and 32 individuals without urolithiasis (group B, control group) were enrolled into our study. Level of fetuin-A in serum and urine was measured by ELISA, and expression of fetuin-A in renal tissue was localized and assessed by immunohistochemistry, real-time polymerase chain reaction, and Western blotting, respectively. Indexes of oxidative stress in kidney were evaluated. Other routine serum and urine chemistries for inpatients were measured biochemically. The results showed that fetuin-A expressed widely in the proximal and distal renal tubule, the thin segment of Henle's loop and the collecting duct epithelium. There were no differences in serum fetuin-A level between the two groups. Compared with control group, cellular expression of P47phox and fetuin-A mRNAs in the renal tissue of patients with nephrolithiasis increased, the level of MDA in renal tissue and the level of urinary calcium also increased, but urinary and renal fetuin-A protein and the activities of SOD in renal tissue decreased. Correlation analysis showed that there was a negative correlation between the level of renal fetuin-A protein and the expression of P47phox mRNA and MDA. These results revealed that nephrolithiasis patients had lower fetuin-A protein level in urine and renal tissue.

Taurine protected kidney from oxidative injury through mitochondrial-linked pathway in a rat model of nephrolithiasis.

Hyperoxaluria and crystal deposition induce oxidative stress (OS) and renal epithelial cells injury, both mitochondria and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase are considered as the main sources of reactive oxygen species (ROS). Taurine is known to have antioxidant activity and shows renoprotective effect. We investigate the effect of taurine treatment on renal protection, and the putative source of ROS, in a rat model of calcium oxalate nephrolithiasis. Rats were administered with 2.5% (V/V) ethylene glycol + 2.5% (W/V) ammonium chloride (4 ml/day), with restriction on intake of drinking water (20 ml/day) for 4 weeks. Simultaneous treatment with taurine (2% W/W, mixed with the chow) was performed. At the end of the study, indexes of OS and renal injury were assessed. Renal tubular ultrastructure changes were analyzed under transmission electron microscopy. Crystal deposition in kidney was scored under light microscopy. Angiotensin II in kidney homogenates was determined by radioimmunoassay. Expression of NADPH oxidase subunits p47phox and Nox-4 mRNAs in kidney was evaluated by real time-polymerase chain reaction. The data showed that oxidative injury of the kidney occurred in nephrolithiasis-induced rats. Hyperplasia of mitochondria developed in renal tubular epithelium. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in mitochondria decreased and the mitochondrial membrane showed oxidative injury. Taurine treatment alleviated the oxidative injury of the kidney, improved SOD and GSH-Px activities, as well as the mitochondrial membrane injury, with lesser crystal depositions in the kidney. We could not detect statistical changes in the renal angiotensin II level, and the renal p47phox and Nox-4 mRNAs expression in those rats. The results suggest that mitochondria but not NADPH oxidase may account for the OS and taurine protected kidney from oxidative injury through mitochondrial-linked pathway in this rat model.

Effects of apocynin and losartan treatment on renal oxidative stress in a rat model of calcium oxalate nephrolithiasis.

BACKGROUND: Tissue culture studies found that renal epithelial cells suffer oxidative injury on exposure to high levels of oxalate (Ox) and calcium oxalate (CaOx) crystals; nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, a major source of reactive oxygen species (ROS) production in kidney, has been shown to be involved in this event. The present study aimed to investigate whether this in vitro feature of NADPH oxidase could be confirmed in vivo. METHODS: Animal model of nephrolithiasis was established in adult male Sprague-Dawley rats by administration of 0.8% ethylene glycol (EG) in drinking water for 4 weeks. Simultaneous treatment with apocynin (0.2 g kg(-1) day(-1)) or losartan (30 mg kg(-1) day(-1)) by intragastric administration was performed in rats. At the end of the study, urinary 8-IP, a product of lipid peroxidation, and enzymatic activity of superoxide dismutase (SOD) in kidney homogenates were assessed as markers for state of renal oxidative stress (OS). Expression of NADPH oxidase subunit p47phox in kidney was localized and evaluated by immunohistochemistry, real-time polymerase chain reaction (PCR), and Western blotting. The concentration of angiotensin II in kidney homogenates was determined using radioimmunoassay method. RESULTS: Compared with control, OS developed significantly in rats received EG, with increased expression of p47phox messenger RNA (mRNA) and protein in kidneys. Renal angiotensin II also increased significantly. Treatment with apocynin or losartan significantly reduced excretion of urinary 8-IP, restored SOD activity, with decrease in expression of p47phox in kidney, but levels of those OS markers in apocynin- or losartan-treated rats were still higher than in normal controls. CONCLUSIONS: These results suggest that renal Ang II and its stimulation of NADPH oxidase may partially account for the development of OS in kidney in this rat model of CaOx nephrolithiasis.

[The antiplatelet effect of clopidogrel is not attenuated by statin treatment in patients with acute coronary syndromes undergone coronary stenting].

OBJECTIVE: To evaluate the interaction of atorvastatin or pravastatin with clopidogrel on platelet activation and aggregation function in patients with acute coronary syndromes (ACS) undergoing coronary stenting. METHODS: Between April and December 2006, a total of 150 hospitalized ACS patients undergoing coronary stenting were randomized to receive atorvastatin (n = 50), pravastatin (n = 50) or no statin (n = 50) one day post procedure. All patients received standard antiplatelet treatment including aspirin 300 mg/d and loading dose 300 mg of clopidogrel followed by maintenance dose 75 mg/d. The expressions of CD62P and PAC-1 and the maximal platelet aggregation rate (MPAR) induced by 20 micromol/L ADP were measured at day 1 before statin therapy (baseline) and day 3 after procedure. RESULTS: Baseline clinical characteristics and levels of CD62P, PAC-1 and MPAR at the baseline were comparable among three groups. After 3-day statin treatment, the changes of CD62P [(4.69 +/- 16.78)% vs. (1.35 +/- 10.86)% vs. (2.97 +/- 10.21)%], PAC-1 [(12.78 +/- 22.07)% vs. (8.01 +/- 21.23)% vs. (10.65 +/- 21.39)%] and MPAR [(5.44 +/- 18.68)% vs. (7.15 +/- 19.59)% vs. (3.76 +/- 23.42)%] among three groups were not significantly different (all P > 0.05). Subgroup analysis showed that DeltaCD62P [(7.50 +/- 19.35)% vs. (3.24 +/- 11.18)% vs. (2.53 +/- 8.87)%], DeltaPAC-1 [(13.40 +/- 24.62)% vs. (11.28 +/- 19.90)% vs. (10.11 +/- 21.29)%] and DeltaMPAR [(7.56 +/- 19.11)% vs. (7.87 +/- 23.60)% vs. (6.75 +/- 23.30)%] in ACS patients were also similar among three groups (all P > 0.05). CONCLUSION: Neither atorvastatin nor pravastatin attenuates the antiplatelet function of clopidogrel in ACS patients early post coronary stenting.

[Application of ultrasonic angioplasty in treating totally occluded peripheral arteries, a clinical study of 39 cases].

OBJECTIVE: To evaluate the efficacy and safety of intravascular ultrasonic angioplasty in treating atherosclerotic totally occluded peripheral arteries. METHODS: Percutaneous ultrasonic angioplasty was applied on 39 cases with peripheral atherosclerotic total occlusion under fluoroscopic guidance. The recanalization, clinical efficacy and complications were observed. RESULTS: 38 (97.4%) of the 39 cases achieved successful recanalization in (1157 +/- 376) seconds, with a mean residual stenosis of (32 +/- 11)%. The technical successful rate (residual stenosis < 50%) was 82.1% (32/39). Clinical improvement at different degrees was seen in 38 cases after ultrasonic angioplasty. The patency rates 24 hours, 30 days, 90 days and 180 days after the ultrasonic angioplasty were 100%, 94.7%, 89.5% and 81.6% respectively. The complications related to ultrasonic angioplasty included hemoglobinuria in 9 cases and distal embolization in 1 case. CONCLUSION: Ultrasonic angioplasty appears to be safe and effective for the treatment of atherosclerotic totally occluded peripheral arteries.