Interaction between Nobiliside-a and lipid bilayers

Nobiliside A (Nob) is a new triterpenoid saponin first discovered and isolated from the Holothuria nobilis with chemical molecular structure of C54H87O26 SNa. Extracorporeal antitumor test showed that Nob may be a new category of effective anticancer medicine which had excellent cytotoxicity as well as inhibited vascular endothelial cell (VEC) proliferation and migration in vitro and chicken chorioallantoic membrane (CAM) angiogenesis in vivo at a lower dose. Unfortunately, the clinical application of Nob was severely limited by the low bioavailability of Nob after oral administration, and highly toxic especially heart toxicity and the ability causing hemolysis of blood cells after intravenous injection. To reduce the hemolysis and toxicity of Nob after intravenous injection, liposomes were used as its carriers and good effect was acquired in our previous study. During the preparation and study of Nob liposomes, we found that Nob liposomes had high encapsulation efficiency (EE), which nearly 100 % and good stability. It was proposed that there would be strong interaction between Nob and lipid bilayers, which would affect the EE, the stability, pharmacokinetics, pharmacodynamics and even the toxicity of the drug. Thus, fourier transformer infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), fluoroscense spectroscopy were used to study the interaction between Nob and lipid bilayers. The results showed that there was a strong interaction between Nob and both phospholipids (PL) and cholesterol (CH) in lipid bilayers, and the interaction between Nob and CH was stronger than that between Nob and PL. There was also interaction between PL and CH, which would be decreased when Nob existed. Thus, the reason of Nob liposomes having high EE and good stability could be infered from the study. In fluoroscense spectroscopy study it was found that Nob could destroy calcein liposomes and lead release of the content, while Nob encapsuled in liposomes could not cause the destruction of calcein liposomes. These phenomena were different with Nob liposomes leading to the content release from red blood cells, so the mechanism of Nob liposomes decreasing the toxicity to mice and hemolysis in vitro should be further studied.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Interaction between Nobiliside-a and lipid bilayers

Nobiliside A (Nob) is a new triterpenoid saponin first discovered and isolated from the Holothuria nobilis with chemical molecular structure of C54H87O26 SNa. Extracorporeal antitumor test showed that Nob may be a new category of effective anticancer medicine which had excellent cytotoxicity as well as inhibited vascular endothelial cell (VEC) proliferation and migration in vitro and chicken chorioallantoic membrane (CAM) angiogenesis in vivo at a lower dose. Unfortunately, the clinical application of Nob was severely limited by the low bioavailability of Nob after oral administration, and highly toxic especially heart toxicity and the ability causing hemolysis of blood cells after intravenous injection. To reduce the hemolysis and toxicity of Nob after intravenous injection, liposomes were used as its carriers and good effect was acquired in our previous study. During the preparation and study of Nob liposomes, we found that Nob liposomes had high encapsulation efficiency (EE), which nearly 100 % and good stability. It was proposed that there would be strong interaction between Nob and lipid bilayers, which would affect the EE, the stability, pharmacokinetics, pharmacodynamics and even the toxicity of the drug. Thus, fourier transformer infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), fluoroscense spectroscopy were used to study the interaction between Nob and lipid bilayers. The results showed that there was a strong interaction between Nob and both phospholipids (PL) and cholesterol (CH) in lipid bilayers, and the interaction between Nob and CH was stronger than that between Nob and PL. There was also interaction between PL and CH, which would be decreased when Nob existed. Thus, the reason of Nob liposomes having high EE and good stability could be infered from the study. In fluoroscense spectroscopy study it was found that Nob could destroy calcein liposomes and lead release of the content, while Nob encapsuled in liposomes could not cause the destruction of calcein liposomes. These phenomena were different with Nob liposomes leading to the content release from red blood cells, so the mechanism of Nob liposomes decreasing the toxicity to mice and hemolysis in vitro should be further studied.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Interaction between Nobiliside-a and lipid bilayers

Nobiliside A (Nob) is a new triterpenoid saponin first discovered and isolated from the Holothuria nobilis with chemical molecular structure of C54H87O26 SNa. Extracorporeal antitumor test showed that Nob may be a new category of effective anticancer medicine which had excellent cytotoxicity as well as inhibited vascular endothelial cell (VEC) proliferation and migration in vitro and chicken chorioallantoic membrane (CAM) angiogenesis in vivo at a lower dose. Unfortunately, the clinical application of Nob was severely limited by the low bioavailability of Nob after oral administration, and highly toxic especially heart toxicity and the ability causing hemolysis of blood cells after intravenous injection. To reduce the hemolysis and toxicity of Nob after intravenous injection, liposomes were used as its carriers and good effect was acquired in our previous study. During the preparation and study of Nob liposomes, we found that Nob liposomes had high encapsulation efficiency (EE), which nearly 100 % and good stability. It was proposed that there would be strong interaction between Nob and lipid bilayers, which would affect the EE, the stability, pharmacokinetics, pharmacodynamics and even the toxicity of the drug. Thus, fourier transformer infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), fluoroscense spectroscopy were used to study the interaction between Nob and lipid bilayers. The results showed that there was a strong interaction between Nob and both phospholipids (PL) and cholesterol (CH) in lipid bilayers, and the interaction between Nob and CH was stronger than that between Nob and PL. There was also interaction between PL and CH, which would be decreased when Nob existed. Thus, the reason of Nob liposomes having high EE and good stability could be infered from the study. In fluoroscense spectroscopy study it was found that Nob could destroy calcein liposomes and lead release of the content, while Nob encapsuled in liposomes could not cause the destruction of calcein liposomes. These phenomena were different with Nob liposomes leading to the content release from red blood cells, so the mechanism of Nob liposomes decreasing the toxicity to mice and hemolysis in vitro should be further studied.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Synthesis and biological activities of novel danshensu amide derivatives as anti-myocardial ischemia agents

A series of novel danshensu amide derivatives were synthesized, and the protective effects of all the compounds on rat myocardial cell lines H9C2 by hypoxia were investigated. The results showed that all the seven compounds could significantly increased cell viability compared with hypoxia group. Among these compounds, 3-(3,4-dimethoxyphenyl)-2-hydroxy-N-propylpropanamide (6) exhibited good activities, with cell viability reached 94.2 % compared to the normal. The novel danshensu amide derivatives, possessing an additional lipophilic alkyl chain showed a good lipophilicity.Colegio de Farmacéuticos de la Provincia de Buenos Aire

The molecular basis of beta-thalassemia intermedia in southern China: genotypic heterogeneity and phenotypic diversity

<p>Abstract</p> <p>Background</p> <p>The clinical syndrome of thalassemia intermedia (TI) results from the β-globin genotypes in combination with factors to produce fetal haemoglobin (HbF) and/or co-inheritance of α-thalassemia. However, very little is currently known of the molecular basis of Chinese TI patients.</p> <p>Methods</p> <p>We systematically analyzed and characterized β-globin genotypes, α-thalassemia determinants, and known primary genetic modifiers linked to the production of HbF and the aggravation of α/β imbalance in 117 Chinese TI patients. Genotype-phenotype correlations were analyzed based on retrospective clinical observations.</p> <p>Results</p> <p>A total of 117 TI patients were divided into two major groups, namely heterozygous β-thalassemia (n = 20) in which 14 were characterized as having a mild TI with the Hb levels of 68-95 g/L except for five co-inherited ααα^anti-3.7triplication and one carried a dominant mutation; and β-thalassemia homozygotes or compound heterozygotes for β-thalassemia and other β-globin defects in which the β⁺-thalassemia mutation was the most common (49/97), hemoglobin E (HbE) variants was second (27/97), and deletional hereditary persistence of fetal hemoglobin (HPFH) or δβ-thalassemia was third (11/97). Two novel mutations, Term CD+32(A→C) and Cap+39(C→T), have been detected.</p> <p>Conclusions</p> <p>Chinese TI patients showed considerable heterogeneity, both phenotypically and genotypically. The clinical outcomes of our TI patients were mostly explained by the genotypes linked to the β- and α-globin gene cluster. However, for a group of 14 patients (13 β⁰/β^Nand 1 β⁺/β^N) with known heterozygous mutations of β-thalassemia and three with homozygous β-thalassemia (β⁰/β⁰), the existence of other causative genetic determinants is remaining to be molecularly defined.</p

Comparison of vomerine tooth rows in juvenile and adult Hynobius guabangshanensis (Urodela: Hynobiidae)

In this note, the vomerine tooth rows of juveniles and adults H. guabangshanensis are described and compared. The vomerine tooth rows are long and posteriorly directed, and arranged in a V-shape in adults while short and slightly arched, parallel to the premaxilla and maxilla in juveniles. The vomerine tooth rows of juveniles are similar to the aquatic salamanders, which feed by suction in water, and the vomerine tooth rows function in hindering escape of prey. The vomerine tooth rows of adults are resemble with terrestrial salamanders, which use inertial feeding or protruding tongue to capture prey, and the vomerine tooth rows function in helding and delivering the prey. Hence, the differences of the vomerine tooth rows reflect the differences of life habit, feeding modes and function among different development peroid

An Entropy Regularization k-Means Algorithm with a New Measure of between-Cluster Distance in Subspace Clustering

Although within-cluster information is commonly used in most clustering approaches, other important information such as between-cluster information is rarely considered in some cases. Hence, in this study, we propose a new novel measure of between-cluster distance in subspace, which is to maximize the distance between the center of a cluster and the points that do not belong to this cluster. Based on this idea, we firstly design an optimization objective function integrating the between-cluster distance and entropy regularization in this paper. Then, updating rules are given by theoretical analysis. In the following, the properties of our proposed algorithm are investigated, and the performance is evaluated experimentally using two synthetic and seven real-life datasets. Finally, the experimental studies demonstrate that the results of the proposed algorithm (ERKM) outperform most existing state-of-the-art k-means-type clustering algorithms in most cases

Deep Neural Networks Based on Span Association Prediction for Emotion-Cause Pair Extraction

The emotion-cause pair extraction task is a fine-grained task in text sentiment analysis, which aims to extract all emotions and their underlying causes in a document. Recent studies have addressed the emotion-cause pair extraction task in a step-by-step manner, i.e., the two subtasks of emotion extraction and cause extraction are completed first, followed by the pairing task of emotion-cause pairs. However, this fail to deal well with the potential relationship between the two subtasks and the extraction task of emotion-cause pairs. At the same time, the grammatical information contained in the document itself is ignored. To address the above issues, we propose a deep neural network based on span association prediction for the task of emotion-cause pair extraction, exploiting general grammatical conventions to span-encode sentences. We use the span association pairing method to obtain candidate emotion-cause pairs, and establish a multi-dimensional information interaction mechanism to screen candidate emotion-cause pairs. Experimental results on a quasi-baseline corpus show that our model can accurately extract potential emotion-cause pairs and outperform existing baselines

Shenqi Fuzheng Injection Reverses Cisplatin Resistance through Mitofusin-2-Mediated Cell Cycle Arrest and Apoptosis in A549/DDP Cells

The goal of this evaluation was to examine the mechanisms of Shenqi Fuzheng injection (SFI), an extract made from the plants Radix Astragali and Radix Codonopsis, in the process of chemotherapy sensitivity in non-small-cell lung cancer (NSCLC) cells. We investigated the expression of mitofusin-2 (Mfn2), a mitochondrial GTPase that may be related to chemoresistance, and found that Mfn2 expression was lower in human cisplatin-resistant lung carcinoma A549/DDP cells than in cisplatin-susceptible A549 cells. Chemosensitivity to cisplatin was restored in A549/DDP cells following supplementation in conjunction with SFI treatment, the effect of which we evaluated via cell cycle, apoptosis, and cell signaling analysis. We found that the combined use of A549/DDP cells with SFI and cisplatin enhanced cell cycle arrested in the G2/M phase, which was accompanied by upregulation of p53 and p21 protein expression and induced mitochondrial apoptosis in conjunction with the upregulation of Bax and the downregulation of Bcl-2 protein expression. Moreover, cell cycle arrest and mitochondrial apoptosis coincided with the upregulation of Mfn2 expression, which, in turn, was related to the increased mitochondrial membrane permeabilization and elevated reactive oxygen species. In summary, our findings suggest that the effect of SFI in increasing chemotherapy sensitivity in cisplatin resistance of NSCLCs occurs through cell cycle arrest and the initiation of mitochondrial apoptosis involved in the upregulation of Mfn2 expression