Novel curcumin analogs were synthesized using Knoevenagel condensation to convert enolic diketones of curcumin into non-enolizable ones and Schiff bases were prepared using a bioactive thiosemicarbazide pharmacophore. Copper(II) conjugates of all synthesized ligands were prepared and structurally characterized as well as evaluated for their potential of inhibiting TNF-induced NF-kappaB activation and proliferation in human leukemic KBM-5 cells wherein compound 13 was found to be more potent than curcumin. Compounds were further examined on other tumor cell lines such as Jurkat, H1299, and MM1, respectively. 相似文献
Single cell network profiling (SCNP) utilizing flow cytometry measures alterations in intracellular signaling responses. Here SCNP was used to characterize Acute Myeloid Leukemia (AML) disease subtypes based on survival, DNA damage response and apoptosis pathways.
Methodology and Principal Findings
Thirty four diagnostic non-M3 AML samples from patients with known clinical outcome were treated with a panel of myeloid growth factors and cytokines, as well as with apoptosis-inducing agents. Analysis of induced Jak/Stat and PI3K pathway responses in blasts from individual patient samples identified subgroups with distinct signaling profiles that were not seen in the absence of a modulator. In vitro exposure of patient samples to etoposide, a DNA damaging agent, revealed three distinct “DNA damage response (DDR)/apoptosis” profiles: 1) AML blasts with a defective DDR and failure to undergo apoptosis; 2) AML blasts with proficient DDR and failure to undergo apoptosis; 3) AML blasts with proficiency in both DDR and apoptosis pathways. Notably, AML samples from clinical responders fell within the “DDR/apoptosis” proficient profile and, as well, had low PI3K and Jak/Stat signaling responses. In contrast, samples from clinical non responders had variable signaling profiles often with in vitro apoptotic failure and elevated PI3K pathway activity. Individual patient samples often harbored multiple, distinct, leukemia-associated cell populations identifiable by their surface marker expression, functional performance of signaling pathway in the face of cytokine or growth factor stimulation, as well as their response to apoptosis-inducing agents.
Conclusions and Significance
Characterizing and tracking changes in intracellular pathway profiles in cell subpopulations both at baseline and under therapeutic pressure will likely have important clinical applications, potentially informing the selection of beneficial targeted agents, used either alone or in combination with chemotherapy. 相似文献
The Influenza A pandemic H1N1 2009 (H1N1pdm) virus appeared in India in May 2009 and thereafter outbreaks with considerable morbidity and mortality have been reported from many parts of the country. Continuous monitoring of the genetic makeup of the virus is essential to understand its evolution within the country in relation to global diversification and to track the mutations that may affect the behavior of the virus.
Methods
H1N1pdm viruses were isolated from both recovered and fatal cases representing major cities and sequenced. Phylogenetic analyses of six concatenated whole genomes and the hemagglutinin (HA) gene of seven more isolates from May-September 2009 was performed with reference to 685 whole genomes of global isolates available as of November 24, 2009. Molecular characterization of all the 8 segments was carried out for known pathogenic markers.
Results
The first isolate of May 2009 belonged to clade 5. Although clade 7 was the dominant H1N1pdm lineage in India, both clades 6 and 7 were found to be co-circulating. The neuraminidase of all the Indian isolates possessed H275, the marker for sensitivity to the neuraminidase inhibitor Oseltamivir. Some of the mutations in HA are at or in the vicinity of antigenic sites and may therefore be of possible antigenic significance. Among these a D222G mutation in the HA receptor binding domain was found in two of the eight Indian isolates obtained from fatal cases.
Conclusions
The majority of the 13 Indian isolates grouped in the globally most widely circulating H1N1pdm clade 7. Further, correlations of the mutations specific to clade 7 Indian isolates to viral fitness and adaptability in the country remains to be understood. The D222G mutation in HA from isolates of fatal cases needs to be studied for pathogenicity. 相似文献
Himalayan alder species are proven to be very useful in traditional as well as contemporary agroforestry practice. These nitrogen-fixing trees are also useful in the land restoration. Therefore, understanding the distribution of Himalayan alder and the potential zone for plantation is meaningful in the agroforestry sector. Suitable climatic zones of Alnus spp. were modelled in MaxEnt software using a subset of least correlated bioclimatic variables for current conditions (1950-2000), topographic variables (DEM derived) and Landuse Landcover (LULC) data. We generated several models and selected the best model against random models using ANOVA and t-test. The environmental variables that best explained the current distribution of the species were identified and used to project into the future. For future projections, ensemble scenarios of climate change projection derived from the results of 19 Earth System Models (ESM) were used. Our model revealed that the most favorable conditions for Alnusnepalensis are in central Nepal in the moist north-west facing slope, whereas for Alnusnitida they are in western Nepal. The major climatic factor that contributes to Alnus species distribution in Nepal appears to be precipitation during the warmest quarter for A. nepalensis and precipitation during the driest quarter for A. nitida. Future projections revealed changes in the probability distribution of these species, as well as where they need conservation and where they can be planted. Also, our model predicts that the distribution of Alnus spp. in hilly regions will remain unchanged, and therefore may represent sites that can be used to revitalize traditional agroforestry systems and extract source material for land restoration. 相似文献
The ability of Fe3O4 Fenton-like reaction to produce glucose from lignocellulosic biomass was investigated. Fe3O4 magnetite nanoparticles were chemically synthesized from iron salts (a mixture of 1 M FeCl2 and 2M FeCl3) using an ammonia solution (30% NH4OH). The synthesized Fe3O4 nanoparticles were further characterized by X-ray photoelectron spectroscopy, energy dispersive X-ray spectroscopy, scanning electron microscopy, and transmission electron microscopy. Reed stems and rice straw biomasses pretreated with optimized Fenton-like reagents (Fe3O4 and H2O2) increased glucose production by 177 and 87%, respectively, compared to the control without the catalysts. 相似文献
Introduction: Although it is possible to identify the genetic risk for type 1 diabetes (T1D), it is not possible to predict who will develop the disease. New biomarkers are needed that would help understand the mechanisms of disease onset and when to administer targeted therapies and interventions.
Areas covered: An overview is presented of international study efforts towards understanding the cause of T1D, including the collection of several extensive temporal sample series that follow the development of T1D in at risk children. The results of the proteomics analysis of these materials are presented, which have included bodily fluids, such as serum or plasma and urine, as well as tissue samples from the pancreas.
Expert commentary: Promising recent reports have indicated detection of early proteomic changes in the serum of patients prior to diagnosis, potentially providing new measures for risk assessment. Similarly, there has been evidence that post-translational modification (PTM) may result in the recognition of islet cell proteins as autoantigens; modified proteins could thus be used as targets for immunomodulation to overcome the threat of the autoimmune response. 相似文献
Chitosan is a widely employed polysaccharide with positive zeta-potential and better tissue/cell adhesion. Its hydrophilicity, high viscosity, and insolubility at physiological pH are major hurdles in proper utilization of this macromolecule. Therefore, it was conjugated with biocompatible stearic acid and the conjugate was employed to develop polymeric micelles for delivery of tamoxifen to breast cancer cells. The conjugate was characterized by FT-IR and NMR, and the nanocarrier was characterized for micromeritics, surface charge, drug loading, and morphological attributes. The efficacy was evaluated by in vitro MTT studies, safety by erythrocyte compatibility, and biodistribution by in vivo pharmacokinetic studies. Despite better drug loading and sustained drug release, cytotoxicity on MCF-7 breast cancer cells was substantially enhanced and the pharmacokinetic profile was significantly modified. The AUC was enhanced manifolds along with reduced clearance. The findings are unique and provide an alternative to the conventional lipid-based nanocarriers for better dose delivery, tissue adhesion, and desired pharmacokinetic modulation. 相似文献
The metal-insulator-metal (MIM) waveguides are considered best among all plasmonic waveguides for propagation of optical signal to deep sub-wavelength scale. In this paper, MIM plasmonic waveguides based Mach-Zehnder interferometer (MZI) is developed. It possesses nonlinear Kerr material in one of its linear arm for controlling of optical signal with light intensity. Self phase modulation (SPM) and cross phase modulation (XPM) processes inside nonlinear MZI are used to design novel and compact full-adder and full-subtractor. Analysis and verification of proposed devices are carried out using FDTD and MATLAB simulations. 相似文献
Crimean-Congo hemorrhagic fever (CCHF) virus is one among the major zoonosis viral diseases that use the Hyalomma ticks as their transmission vector to cause viral infection to the human and mammalian community. The fatality of infectious is high across the world especially in Africa, Asia, Middle East, and Europe. This study regarding codon usage bias of S, M, and L segments of the CCHF virus pertaining to the host Homo sapiens, reveals in-depth information about the evolutionary characteristics of CCHFV. Relative Synonymous Codon Usage (RSCU), Effective number of codons (ENC) were calculated, to determine the codon usage pattern in each segment. Correlation analysis between Codon adaptation index (CAI), GRAVY (Hydrophobicity), AROMO (Aromaticity), and nucleotide composition revealed bias in the codon usage pattern. There was no strong codon bias found among any segments of the CCHF virus, indicating both the factors i.e., natural selection and mutational pressure shapes the codon usage bias. 相似文献