The acute toxicity of tri-n-butyltin taurocholate

The acute toxicity for tri-n-butyltin taurocholate (TBT-TA), a newly synthesized organotin steroid, was determined using Long Evans rats. The organotin compound was suspended in corn oil and administered by gavage using standard techniques. The TBT-TA exhibited a taurocholic acid toxicity at 24 h and a tributyltin toxicity at three days. The LD₅₀ values were 611 and 384 mg kg^?1 respectively. The dead rats exhibited distended stomachs, enlarged cecums, and lesions in the gastrointestinal tract. The toxicity is similar to that observed with other trialkyltin compounds.     

Bipartite network analysis reveals metabolic gene expression profiles that are highly associated with the clinical outcomes of acute myeloid leukemia

Dysregulated and reprogrammed metabolism are one of the most important characteristics of cancer, and exploiting cancer cell metabolism can aid in understanding the diverse clinical outcomes for patients. To investigate the differences in metabolic pathways among patients with acute myeloid leukemia (AML) and differential survival outcomes, we systematically conducted microarray data analysis of the metabolic gene expression profiles from 384 patients available from the Gene Expression Omnibus and Cancer Genome Atlas databases. Pathway enrichment analysis of differentially expressed genes (DEGs) showed that the metabolic differences between low-risk and high-risk patients mainly existed in two pathways: biosynthesis of unsaturated fatty acids and oxidative phosphorylation. Using the gene-pathway bipartite network, 62 metabolic genes were identified from 272 DEGs involved in 88 metabolic pathways. Based on the expression patterns of the 62 genes, patients with shorter overall survival (OS) durations in the training set (hazard ratio (HR) = 1.58, p = 0.038) and in two test sets (HR = 1.69 and 1.56 and p = 0.089 and 0.029, respectively) were well discriminated by hierarchical clustering analysis. Notably, the expression profiles of ALAS2, BCAT1, BLVRB, and HK3 showed distinct differences between the low-risk and high-risk patients. In addition, models for predicting the OS outcome of AML from the 62 gene signatures achieved improved performance compared with previous studies. In conclusion, our findings reveal significant differences in metabolic processes of patients with AML with diverse survival durations and provide valuable information for clinical translation.     

Genotyping of two single nucleotide polymorphisms in 5,10-methylenetetrahydrofolate reductase by multiplex polymerase chain reaction and capillary electrophoresis

Two single nucleotide polymorphisms (SNPs) of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, A1298C and C677T, were widely considered to be related with various neoplasia disorders. We established a simple and effective capillary electrophoresis (CE) method for detection of two SNPs in MTHFR gene simultaneously. DNA samples were amplified by multiplex PCR with universal fluorescence-labeled primer and analyzed by single-strand conformation polymorphism (SSCP)-CE method. The CE method was performed using 1.5% hydroxyethyl cellulose in 1× TBE buffer containing 1 M urea. The PCR products after SSCP procedure were electrokinetically injected at −10 kV, 30 s. Separation voltage was −6 kV and the temperature was set at 20 °C. The optimal SSCP-CE method was applied to detect two polymorphisms in MTHFR gene of acute lymphoblastic leukemia (ALL) and attention-deficit/hyperactivity disorder (ADHD) patients. Genotyping results were evaluated in terms of relationships between outcomes for ADHD patients after ALL chemotherapy and ALL disease. The SSCP-CE method and multiplex PCR with universal fluorescence primer were used as the fast technique for screening two SNPs in MTHFR gene, A1298C and C677T. The genotyping data were coincident with DNA sequencing. This SSCP-CE method was found feasible for detecting mutation of MTHFR gene in populations.     

Qualitative and quantitative determination of polyacetylenes in different Bupleurum species by high performance liquid chromatography with diode array detector and mass spectrometry

Polyacetylenes are main toxic ingredients in Bupleurum longiradiatum, a poisonous plant that has ever been misused as substitutes for Chaihu (Bupleuri Radix). For the first time, a high-performance liquid chromatography method coupled with diode array detector and mass spectrometry (HPLC-DAD-MS) was developed for qualitative and quantitative analysis of nine polyacetylenes in Bupleurum species. All references, including two new polyacetylenes, were isolated from B. longiradiatum and purified using a semi-preparation HPLC chromatography. The analysis was performed on a TSKgel ODS-100V C18 column (3 μm, 150 mm x 4.6 mm i.d.) using a gradient system of acetonitrile and water, with diode array detection (254 nm). The method was validated for linearity, precision, accuracy, limit of detection and quantification. A total of 27 Bupleurum samples were examined with this method, which showed a great variety in the distribution and contents of the polyacetylenes. It was found that polyacetylenes (1-8) were the main ingredients in B. longiradiatum, while a few kinds of polyacetylenes (5-8) were also identified in B. smithii, B. smithii var. parvifolium, B. bicaule and B. angustissimum. However, no polyacetylenes (1-9) were detected in the authentic Chaihu samples and the other Bupleurum species. The results indicated that the toxic B. longiradiatum could readily be distinguished from other medicinal Bupleurum species based on the polyacetylene profiles, and the guidelines and quality control of polyacetylenes for Chaihu are useful. The acute toxicity of the ethanol extract of B. longiradiatum and its fractions was also investigated.     

In vivo mechanical study of helical cardiac pacing electrode interacting with canine myocardium

Cardiac pacing is a medical device to help human to overcome arrhythmia and to recover the regular beats of heart. A helical configuration of electrode tip is a new type of cardiac pacing lead distal tip. The helical electrode attaches itself to the desired site of heart by screwing its helical tip into the myocardium. In vivo experiments on anesthetized dogs were carried out to measure the acute interactions between helical electrode and myocardium during screw-in and pull-out processes. These data would be helpful for electrode tip design and electrode/myocardium adherence safety evaluation. They also provide reliability data for clinical site choice of human heart to implant and to fix the pacing lead. A special design of the helical tip using strain gauges is instrumented for the measurement of the screw-in and pull-out forces. We obtained the data of screw-in torques and pull-out forces for five different types of helical electrodes at nine designed sites on ten canine hearts. The results indicate that the screw-in torques increased steplike while the torque–time curves presente saw-tooth fashion. The maximum torque has a range of 0.3–1.9 N mm. Obvious differences are observed for different types of helical tips and for different test sites. Large pull-out forces are frequently obtained at epicardium of left ventricle and right ventricle lateral wall, and the forces obtained at right ventricle apex and outflow tract of right ventricle are normally small. The differences in pull-out forces are dictated by the geometrical configuration of helix and regional structures of heart muscle.     

Concise synthesis of dopexamine dihydrochloride via benzyl protecting protocol

Benzyl protecting protocol was first employed in two routes for the concise synthesis of dopexamine dihydrochloride.This protecting group could be cleanly removed under mild condition and no unacceptable ion was brought to the final product.The total yield of route I was 43.8% from phenylacetic acid,while it was 54.1% of route II from 2-(3,4-bis(benzyloxy)phenyl)acetic acid.The titration purity of the final product was more than 99.5%,while any single or total impurities met the known standard of the drug by HPLC analysis.The measured residual palladium met an acceptable limit(<1 ppm) as an API for injection.     

Hypoxia-Induced Pro-Protein Therapy Assisted by a Self-Catalyzed Nanozymogen

The success of intracellular protein therapy demands efficient delivery and selective protein activity in diseased cells. Therefore, a cascaded nanozymogen consisting of a hypoxia-activatable pro-protein, a hypoxia-inducing protein, and a hypoxia-strengthened intracellular protein delivery nanovehicle was developed. RPAB, an enzymatically inactive pro-protein of RNase, reversibly caged with hypoxia-cleavable azobenzene, was delivered with glucose oxidase (GOx) using hypoxia-responsive nanocomplexes (NCs) consisting of azobenzene-cross-linked oligoethylenimine (AOEI) and hyaluronic acid (HA). Upon NC-mediated delivery into cancer cells, GOx catalyzed glucose decomposition and aggravated tumoral hypoxia, which drove the recovery of RPAB back to the hydrolytically active RNase and expedited the degradation of AOEI to release more protein cargoes. Thus, the catalytic reaction of the nanozymogen was self-accelerated and self-cycled, ultimately leading to a cooperative anti-cancer effect between GOx-mediated starvation therapy and RNase-mediated pro-apoptotic therapy.