459 research outputs found
A novel thiazolidine compound induces caspase-9 dependent apoptosis in cancer cells
Cataloged from PDF version of article.The forward chemogenomics strategy allowed us to identify a potent cytotoxic thiazolidine compound as an apoptosis-inducing agent. Chemical structures were designed around a thiazolidine ring, a structure already noted for its anticancer properties. Initially, we evaluated these novel compounds on liver, breast, colon and endometrial cancer cell lines. The compound 3 (ALC67) showed the strongest cytotoxic activity (IC50 ∼5 μM). Cell cycle analysis with ALC67 on liver cells revealed SubG1/G1 arrest bearing apoptosis. Furthermore we demonstrated that cytotoxicity of this compound was due to the activation of caspase-9 involved apoptotic pathway, which is death receptor independent. © 2012 Elsevier Ltd. All rights reserve
Dual functionality of conjugated polymer nanoparticles as an anticancer drug carrier and a fluorescent probe for cell imaging
Cataloged from PDF version of article.Multifunctional nanoparticles based on a green emitting, hydrophobic conjugated polymer, poly[(9,9-bis{propeny}fluorenyl-2,7-diyl)-co-(1,4- benzo-{2,1,3}-thiodiazole)] (PPFBT), that acts both as a fluorescent reporter and a matrix to accommodate an anti-cancer compound, camptothecin (CPT), were prepared, characterized and their potential as a fluorescent probe for cell imaging and as a drug delivery vehicle were evaluated via in vitro cell assays. The cell viability of human hepatocellular carcinoma cell line (Huh7) was investigated in the absence and presence of CPT with sulforhodamine B (SRB) and real-time cell electronic sensing (RT-CES) cytotoxicity assays
Anisotropic Strain Induced Soliton Movement Changes Stacking Order and Bandstructure of Graphene Multilayers
The crystal structure of solid-state matter greatly affects its electronic
properties. For example in multilayer graphene, precise knowledge of the
lateral layer arrangement is crucial, since the most stable configurations,
Bernal and rhombohedral stacking, exhibit very different electronic properties.
Nevertheless, both stacking orders can coexist within one flake, separated by a
strain soliton that can host topologically protected states. Clearly, accessing
the transport properties of the two stackings and the soliton is of high
interest. However, the stacking orders can transform into one another and
therefore, the seemingly trivial question how reliable electrical contact can
be made to either stacking order can a priori not be answered easily. Here, we
show that manufacturing metal contacts to multilayer graphene can move solitons
by several m, unidirectionally enlarging Bernal domains due to arising
mechanical strain. Furthermore, we also find that during dry transfer of
multilayer graphene onto hexagonal Boron Nitride, such a transformation can
happen. Using density functional theory modeling, we corroborate that
anisotropic deformations of the multilayer graphene lattice decrease the
rhombohedral stacking stability. Finally, we have devised systematics to avoid
soliton movement, and how to reliably realize contacts to both stacking
configurations
Therapeutic plasma exchange in children with acute liver failure: assessment of laboratory parameters
A small library of chalcones induce liver cancer cell death through Akt phosphorylation inhibition
Hepatocellular carcinoma (HCC) ranks as the fifth most common and the second deadliest cancer worldwide. HCC is extremely resistant to the conventional chemotherapeutics. Hence, it is vital to develop new treatment options. Chalcones were previously shown to have anticancer activities in other cancer types. In this study, 11 chalcones along with quercetin, papaverin, catechin, Sorafenib and 5FU were analyzed for their bioactivities on 6 HCC cell lines and on dental pulp stem cells (DPSC) which differentiates into hepatocytes, and is used as a model for untransformed control cells. 3 of the chalcones (1, 9 and 11) were selected for further investigation due to their high cytotoxicity against liver cancer cells and compared to the other clinically established compounds. Chalcones did not show significant bioactivity ([Formula: see text]) on dental pulp stem cells. Cell cycle analysis revealed that these 3 chalcone-molecules induced SubG1/G1 arrest. Akt protein phosphorylation was inhibited by these molecules in PTEN deficient, drug resistant, mesenchymal like Mahlavu cells leading to the activation of p21 and the inhibition of NF[Formula: see text]B-p65 transcription factor. Hence the chalcones induced apoptotic cell death pathway through NF[Formula: see text]B-p65 inhibition. On the other hand, these molecules triggered p21 dependent activation of Rb protein and thereby inhibition of cell cycle and cell growth in liver cancer cells. Involvement of PI3K/Akt pathway hyperactivation was previously described in survival of liver cancer cells as carcinogenic event. Therefore, our results indicated that these chalcones can be considered as candidates for liver cancer therapeutics particularly when PI3K/Akt pathway involved in tumor development
A deep learning approach for complex microstructure inference
Automated, reliable, and objective microstructure inference from micrographs is essential for a comprehensive understanding of process-microstructure-property relations and tailored materials development. However, such inference, with the increasing complexity of microstructures, requires advanced segmentation methodologies. While deep learning offers new opportunities, an intuition about the required data quality/quantity and a methodological guideline for microstructure quantification is still missing. This, along with deep learning’s seemingly intransparent decision-making process, hampers its breakthrough in this field. We apply a multidisciplinary deep learning approach, devoting equal attention to specimen preparation and imaging, and train distinct U-Net architectures with 30–50 micrographs of different imaging modalities and electron backscatter diffraction-informed annotations. On the challenging task of lath-bainite segmentation in complex-phase steel, we achieve accuracies of 90% rivaling expert segmentations. Further, we discuss the impact of image context, pre-training with domain-extrinsic data, and data augmentation. Network visualization techniques demonstrate plausible model decisions based on grain boundary morphology
Genetic analysis of the partial m rna segment of crimean-congo hemorrhagic fever viruses in turkey
A novel thiazolidine compound induces caspase-9 dependent apoptosis in cancer cells
The forward chemogenomics strategy allowed us to identify a potent cytotoxic thiazolidine compound as an apoptosis-inducing agent. Chemical structures were designed around a thiazolidine ring, a structure already noted for its anticancer properties. Initially, we evaluated these novel compounds on liver, breast, colon and endometrial cancer cell lines. The compound 3 (ALC67) showed the strongest cytotoxic activity (IC50 ∼5 μM). Cell cycle analysis with ALC67 on liver cells revealed SubG1/G1 arrest bearing apoptosis. Furthermore we demonstrated that cytotoxicity of this compound was due to the activation of caspase-9 involved apoptotic pathway, which is death receptor independent. © 2012 Elsevier Ltd. All rights reserved
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Combined transcriptomic-(1)H NMR metabonomic study reveals yhat monoethylhexyl phthalate stimulates adipogenesis and glyceroneogenesis in human adipocytes
Adipose tissue is a major storage site for lipophilic environmental contaminants. The environmental metabolic disruptor hypothesis postulates that some pollutants can promote obesity or metabolic disorders by activating nuclear receptors involved in the control of energetic homeostasis. In this context, monoethylhexyl phthalate (MEHP) is of particular concern since it was shown to activate the peroxisome proliferator-activated receptor γ (PPARγ) in 3T3-L1 murine preadipocytes. In the present work, we used an untargeted, combined transcriptomic-(1)H NMR-based metabonomic approach to describe the overall effect of MEHP on primary cultures of human subcutaneous adipocytes differentiated in vitro. MEHP stimulated rapidly and selectively the expression of genes involved in glyceroneogenesis, enhanced the expression of the cytosolic phosphoenolpyruvate carboxykinase, and reduced fatty acid release. These results demonstrate that MEHP increased glyceroneogenesis and fatty acid reesterification in human adipocytes. A longer treatment with MEHP induced the expression of genes involved in triglycerides uptake, synthesis, and storage; decreased intracellular lactate, glutamine, and other amino acids; increased aspartate and NAD, and resulted in a global increase in triglycerides. Altogether, these results indicate that MEHP promoted the differentiation of human preadipocytes to adipocytes. These mechanisms might contribute to the suspected obesogenic effect of MEHP
Distribution of Spoligotyping Defined Genotypic Lineages among Drug-Resistant Mycobacterium tuberculosis Complex Clinical Isolates in Ankara, Turkey
Background: Investigation of genetic heterogeneity and spoligotype-defined lineages of drug-resistant Mycobacterium tuberculosis clinical isolates collected during a three-year period in two university hospitals and National Tuberculosis Reference and Research Laboratory in Ankara, Turkey. Methods and Findings: A total of 95 drug-resistant M. tuberculosis isolates collected from three different centers were included in this study. Susceptibility testing of the isolates to four major antituberculous drugs was performed using proportion method on Löwenstein–Jensen medium and BACTEC 460-TB system. All clinical isolates were typed by using spoligotyping and IS6110-restriction fragment length polymorphism (RFLP) methods. Seventy-three of the 95 (76.8%) drug resistant M. tuberculosis isolates were isoniazid-resistant, 45 (47.4%) were rifampicin-resistant, 32 (33.7%) were streptomycinresistant and 31 (32.6%) were ethambutol-resistant. The proportion of multidrug-resistant isolates (MDR) was 42.1%. By using spoligotyping, 35 distinct patterns were observed; 75 clinical isolates were grouped in 15 clusters (clustering rate of 79%) and 20 isolates displayed unique patterns. Five of these 20 unique patterns corresponded to orphan patterns in th
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