Rapamycin sensitizes T-ALL cells to dexamethasone-induced apoptosis

<p>Abstract</p> <p>Background</p> <p>Glucocorticoid (GC) resistance is frequently seen in acute lymphoblastic leukemia of T-cell lineage (T-ALL). In this study we investigate the potential and mechanism of using rapamycin to restore the sensitivity of GC-resistant T-ALL cells to dexamethasone (Dex) treatment.</p> <p>Methods</p> <p>Cell proliferation was detected by 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) assay. Fluorescence-activated cell sorting (FACS) analysis was used to analyze apoptosis and cell cycles. Western blot analysis was performed to test the expression of the downstream effector proteins of mammalian target of rapamycin (mTOR), the cell cycle regulatory proteins, and apoptosis associated proteins.</p> <p>Results</p> <p>10 nM rapamycin markedly increased GC sensitivity in GC-resistant T-ALL cells and this effect was mediated, at least in part, by inhibition of mTOR signaling pathway. Cell cycle arrest was associated with modulation of G₁-S phase regulators. Both rapamycin and Dex can induce up-regulation of cyclin-dependent kinase (CDK) inhibitors of p21 and p27 and co-treatment of rapamycin with Dex resulted in a synergistic induction of their expressions. Rapamycin did not obviously affect the expression of cyclin A, whereas Dex induced cyclin A expression. Rapamycin prevented Dex-induced expression of cyclin A. Rapamycin had a stronger inhibition of cyclin D1 expression than Dex. Rapamycin enhanced GC-induced apoptosis and this was not achieved by modulation of glucocorticoid receptor (GR) expression, but synergistically up-regulation of pro-apoptotic proteins like caspase-3, Bax, and Bim, and down-regulation of anti-apoptotic protein of Mcl-1.</p> <p>Conclusion</p> <p>Our data suggests that rapamycin can effectively reverse GC resistance in T-ALL and this effect is achieved by inducing cell cycles arrested at G₀/G₁phase and activating the intrinsic apoptotic program. Therefore, combination of mTOR inhibitor rapamycin with GC containing protocol might be an attracting new therapeutic approach for GC resistant T-ALL patients.</p

Construction of a series of vectors for high throughput cloning and expression screening of membrane proteins from Mycobacterium tuberculosis

<p>Abstract</p> <p>Background</p> <p>One of the major challenges for membrane protein structural genomics is establishing high-throughput cloning and expression screening methods to obtain enough purified protein in a homogeneous preparation for structural and functional studies. Here a series of ligation independent cloning based vectors were constructed to address this challenge.</p> <p>Results</p> <p>The feasibility of these vectors was tested with 41 putative membrane proteins from <it>Mycobacterium tuberculosis</it>. The efficiency for direct cloning of these target genes from PCR products was 95% (39/41). Over 40% of cloned genes were overexpressed in <it>Escherichia coli </it>BL21 (DE3)-RP codon plus strain in the first round of expression screening. For those proteins which showed no expression, three protein fusion partners were prepared and it was found that each of the target proteins could be overexpressed by at least one of these fusions, resulting in the overexpression of two thirds of the cloned genes.</p> <p>Conclusion</p> <p>This expression platform features high throughput cloning, high flexibility for different constructs, and high efficiency for membrane protein overexpression, and is expected to be useful in membrane protein structural and functional studies.</p

Association between Non-High-Density-Lipoprotein-Cholesterol Levels and the Prevalence of Asymptomatic Intracranial Arterial Stenosis

Objective: The aim of this study was to assess the association between non-high-density-lipoprotein-cholesterol (non-HDL-C) and the prevalence of asymptomatic intracranial arterial stenosis (ICAS). Methods and Results: The Asymptomatic Polyvascular Abnormalities Community (APAC) study is a prospective cohort study based on the Kailuan district (China) population. A total of 5351 eligible subjects, aged ≥40, and without history of stroke or myocardial infarction, were enrolled in this study. Transcranial Doppler Ultrasonography (TCD) was performed on all enrolled subjects for the evaluation of ICAS presence. Out of 5351 patients, 698 subjects showed evidence of ICAS (prevalence of 13.04%). Multivariate analysis showed that non-HDL-C is an independent indicator for the presence of ICAS (OR = 1.15, 95%CI: 1.08 – 1.23), but with a gender difference (P for interaction<0.01): in men, non-HDL-C is an independent indicator for ICAS (multivariate-adjusted OR = 1.28, 95%CI: 1.18–1.39), but not in women (multivariate-adjusted OR = 1.03, 95%CI: 0.93–1.14). Subjects were divided into five subgroups based non-HDL-C levels and these levels correlated linearly with the prevalence of ICAS (P for trend <0.01). Compared with the first quintile, multivariate-adjusted OR (95%CI) of the second, third, fourth and fifth quintiles were: 1.05 (0.71–1.56), 1.33 (0.91–1.95), 1.83 (1.27–2.63), 2.48 (1.72–3.57), respectively. Conclusion: Non-HDL-C is an independent predictor of ICAS prevalence in men but not in women, suggesting that non-HDL-C levels could be used as a surveillance factor in the primary prevention of ischemic stroke, especially in men

Round Robin Test of Residual Resistance Ratio of Nb3Sn Composite Superconductors

In this paper, a round robin test of residual resistance ratio (RRR) is performed for Nb3Sn composite superconductors prepared by an internal tin method by six institutes with the international standard test method described in IEC 61788-4. It was found that uncertainty mainly resulted from determination of the cryogenic resistance from the intersection of two straight lines drawn to fit the voltage versus temperature curve around the resistive transition. The measurement clarified that RRR can be measured with expanded uncertainty not larger than 5% with the coverage factor 2 by using this test method

Fermentation Products of Paenibacillus bovis sp. nov. BD3526 Alleviates the Symptoms of Type 2 Diabetes Mellitus in GK Rats

Gut microbiota is closely related to type 2 diabetes mellitus (T2DM). The gut microbiota of patients with T2DM is significantly different from that of healthy subjects in terms of bacterial composition and diversity. Here, we used the fermentation products of Paenibacillus bovis sp. nov. BD3526 to study the disease progression of T2DM in Goto-kakisaki (GK) rats. We found that the symptoms in GK rats fed the fermentation products of BD3526 were significantly improved. The 16S rRNA sequencing showed that the fermentation products of BD3526 had strong effects on the gut microbiota by increasing the content of Akkermansia. In addition, the interaction of the genus in the gut of the BD3526 group also significantly changed. Additional cytokine detection revealed that the fermentation products of BD3526 can reduce the inflammatory factors in the intestinal mucus of GK rats and thereby inhibit the inflammatory response and ameliorate the symptoms of T2DM

Aroma precursors of cigars from different tobacco parts and origins, and their correlations with sensory characteristics

Cigars are developing rapidly around the world, but the content characteristics of aroma precursors and their contribution to sensory perception have not been fully elucidated. In this study, 69 aroma precursors from 61 tobaccos of different parts and origins were systematically determined, and the sensory characteristics of middle leaves from different origins and their correlation with aroma precursors were evaluated. The results showed that tobacco parts mainly affected amino acid content, and contents of nicotine, oxalic acid, malic acid, isovaleric acid, cystine, glutarnine, glycine, isoleucine, glutamicacid, asparticacid, and fructose-proline were significantly changed. Tobacco origins mainly influenced the contents of amino acids, polyacids and high fatty acids, and sugar alcohols, and significantly affected the contents of myosmine, anabasine, nonanoic acid, propanetriol, mannitol, mannose, glucose, alanine, arginine, glutarnine, glutamicacid, histidine, serine, threonine, tryptophan, fructose-alanine, and fructose-asparagine. The flavor characteristics were prominent by wood aroma, and the style and quality characteristics varied greatly among different origins of middle leaves. There were 34, 21, and 22 aroma precursors with high correlations with flavor, style, and quality characteristics. This study provides support for regulating the content and coordination of aroma precursors in different tobacco parts and origins to improve sensory characteristics

Solution combustion synthesis of a nanometer-scale Co3O4 anode material for Li-ion batteries

A novel solution combustion synthesis of nanoscale spinel-structured Co3O4 powder was proposed in this work. The obtained material was composed of loosely arranged nanoparticles whose average diameter was about 36 nm. The as-prepared cobalt oxide powder was also tested as the anode material for Li-ion batteries and revealed specific capacities of 1060 and 533 mAh.g(-1) after 100 cycles at charge-discharge current densities of 100 and 500 mA.g(-1), respectively. Moreover, electrochemical measurements indicate that even though the synthesized nanomaterial possesses a low active surface area, it exhibits a relatively high specific capacity measured at 100 mA.g(-1) after 100 cycles and a quite good rate capability at current densities between 50 and 5000 mA.g(-1).Web of Science1243142

Research progress on extraction, purification, structure and biological activity of Dendrobium officinale polysaccharides

Dendrobium officinale Kimura et Migo (D. officinale) is a traditional medicinal and food homologous plant that has been used for thousands of years in folk medicine and nutritious food. Recent studies have shown that polysaccharide is one of the main biologically active components in D. officinale. D. officinale polysaccharides possess several biological activities, such as anti-oxidant, heptatoprotective, immunomodulatory, gastrointestinal protection, hypoglycemic, and anti-tumor activities. In the past decade, polysaccharides have been isolated from D. officinale by physical and enzymatic methods and have been subjected to structural characterization and activity studies. Progress in extraction, purification, structural characterization, bioactivity, structure-activity relationship, and possible bioactivity mechanism of polysaccharides D. officinale were reviewed. In order to provide reference for the in-depth study of D. officinale polysaccharides and the application in functional food and biomedical research