Development of plant based nanoparticles has many advantages over conventional physico-chemical methods and has various applications in medicine and biology. in present study, zinc oxide (Zno) nanoparticles (nps) were synthesized using leaf extracts of two medicinal plants Cassia fistula and Melia azadarach. 0.01 M zinc acetate dihydrate was used as a precursor in leaf extracts of respective plants for NPs synthesis. The structural and optical properties of NPs were investigated by X-ray diffraction (XRD), fourier transform infrared (ftiR) spectroscopy, scanning electron microscope (SeM), ultraviolet-visible spectrophotometer (UV-Vis) and dynamic light scattering (DLS). the antibacterial potential of Zno NPs was examined by paper disc diffusion method against two clinical strains of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) based on the zone of inhibition and minimal inhibitory indices (Mic). change in color of the reaction mixture from brown to white indicated the formation of Zno NPs. UV peaks at 320 nm and 324 nm, and XRD pattern matching that of JCPDS card for ZnO confirmed the presence of pure ZnO NPs. FTIR further confirmed the presence of bioactive functional groups involved in the reduction of bulk zinc acetate to Zno nps. SeM analysis displayed the shape of nps to be spherical whereas DLS showed their size range from 3 to 68 nm. The C. fistula and M. azadarach mediated Zno nps showed strong antimicrobial activity against clinical pathogens compared to standard drugs, suggesting that plant based synthesis of nps can be an excellent strategy to develop versatile and eco-friendly biomedical products. Plant mediated synthesis of nanoparticles (NPs) is a revolutionary technique that has wide range of applications in agriculture, food industry and medicine. NPs synthesized via conventional methods have limited uses in clinical domain due to their toxicity. Due to the physio-chemical properties of plant based NPs, this method also offer an added advantage of increased life span of NPs that overcome the limitations of conventional chemical and physical methods of NPs synthesis 1-3. Plants possess rich genetic variability with respect to number of biomolecules and metabolites like proteins, vitamins, coenzymes based intermediates, phenols, flavonoids and carbohydrates. These plant metabolites contain hydroxyl, carbonyl, and amine functional groups that react with metal ions and reduce their size into nano range. More specifically, flavonoids contain several functional groups and it is believed that-OH group of flavonoids is mainly considered responsible for the reduction of metal ions into NPs 4. These molecules not only help in bioreduction of the ions to the nano scale size, but they also play a pivotal role in the capping of the nanoparticles which is important for stability and biocompatibility 5. Reducing agents such as phenolic compounds, sterols and alkaloids can reduce metal ions into NPs in a single reaction 6 .
BACKGROUND & AIMS Drug repositioning offers a shorter approval process than new drug development. We therefore searched large public datasets of drug-induced gene expression signatures to identify agents that might be effective against hepatocellular carcinoma (HCC). METHODS We searched public databases of mRNA expression patterns reported from HCC specimens from patients, HCC cell lines, and cells exposed to various drugs. We identified drugs that might specifically increase expression of genes that are downregulated in HCCs and reduce expression of genes upregulated in HCCs using a non-parametric, rank-based pattern-matching strategy based on the Kolmogorov–Smirnov statistic. We evaluated the anti-tumor activity of niclosamide and its ethanolamine salt (NEN) in HCC cell lines (HepG2, Huh7, Hep3B, Hep40, and PLC/PRF/5), primary human hepatocytes, and 2 mouse models of HCC. In 1 model of HCC, liver tumor development was induced by hydrodynamic delivery of a sleeping beauty transposon expressing an activated form of Ras (v12) and truncated beta catenin (N90). In another mouse model, patient-derived xenografts were established by implanting HCC cells from patients into livers of immunocompromised mice. Tumor growth was monitored by bioluminescence imaging. Tumor-bearing mice were fed a regular chow diet or a chow diet containing niclosamide or NEN. In a separate experiment using patient-derived xenografts, tumor-bearing mice were given sorafenib (the standard of care for patients with advanced HCC), NEN, or niclosamide alone; a combination of sorafenib and NEN; or a combination sorafenib and niclosamide in their drinking water, or regular water (control), and tumor growth was monitored. RESULTS Based on gene expression signatures, we identified 3 anthelmintics that significantly altered the expression of genes that are up- or down-regulated in HCCs. Niclosamide and NEN specifically reduced the viability of HCC cells: the agents were at least 7-fold more toxic to HCCs than primary hepatocytes. Oral administration of NEN to mice significantly slowed growth of genetically induced liver tumors and patient-derived xenografts, whereas niclosamide did not, coinciding with the observed greater bioavailability of NEN compared with niclosamide. The combination of NEN and sorafenib was more effective at slowing growth of patient-derived xenografts than either agent alone. In HepG2 cells and in patient-derived xenografts, administration of niclosamide or NEN increased expression of 20 genes downregulated in HCC and reduced expression of 29 genes upregulated in the 274-gene HCC signature. Administration of NEN to mice with patient-derived xenografts reduced expression of proteins in the Wnt–beta catenin, STAT3, AKT–mTOR, EGFR–Ras–Raf signaling pathways. Using immunoprecipitation assays, we found NEN to bind cell division cycle 37 (CDC37) protein and disrupt its interaction with heat shock protein 90 (HSP90). Conclusions In a bioinformatics search for agents that alter the HCC-specific gene expression pattern, we identif...
Based on a newly established sequencing strategy featured by its efficiency, simplicity, and easy manipulation, the sequences of four novel cyclotides (macrocyclic knotted proteins) isolated from an Australian plant Viola hederaceae were determined. The three-dimensional solution structure of V. hederaceae leaf cyclotide-1 (vhl-1), a leaf-specific expressed 31-residue cyclotide, has been determined using two-dimensional 1 H NMR spectroscopy. vhl-1 adopts a compact and well defined structure including a distorted triple-stranded -sheet, a short 3 10 helical segment and several turns. It is stabilized by three disulfide bonds, which, together with backbone segments, form a cyclic cystine knot motif. The three-disulfide bonds are almost completely buried into the protein core, and the six cysteines contribute only 3.8% to the molecular surface. A pH titration experiment revealed that the folding of vhl-1 shows little pH dependence and allowed the pK a of 3.0 for Glu 3 and ϳ5.0 for Glu 14 to be determined. Met 7 was found to be oxidized in the native form, consistent with the fact that its side chain protrudes into the solvent, occupying 7.5% of the molecular surface. vhl-1 shows anti-HIV activity with an EC 50 value of 0.87 M.
The microbial communities transported by Asian desert dust (KOSA) events have attracted much attention as bioaerosols because the transported microorganisms are thought to influence the downwind ecosystems in Korea and Japan. We have analyzed bioaerosol samples collected at 10 and 800 m above the ground within the KOSA source area, Dunhuang City, China. The samples were studied by epifluorescent microscopy, revealing the presence of bacterial cells attached to mineral particles. The microorganisms in the bioaerosol samples were able to grow in media containing up to 20% NaCl, suggesting that bacteria tolerant to high salinities remain viable in the atmosphere. Phylogenetic analysis using 16S rDNA sequences revealed that halobacterial communities in the bioaerosol samples collected at both 10 and 800 m above the ground comprised a few bacterial species related to Bacillus pumilus and Staphylococcus spp. The active mixing processes of the boundary layer presumably transports viable halotolerant bacteria into the free atmosphere, where the long-range atmospheric transport of desert dust is frequently observed.
The nitrogen-fixing symbiosis between cyanobacteria and the water fern Azolla microphylla is, in contrast to other cyanobacteria-plant symbioses, the only one of a perpetual nature. The cyanobacterium is vertically transmitted between the plant generations, via vegetative fragmentation of the host or sexually within megasporocarps. In the latter process, subsets of the cyanobacterial population living endophytically in the Azolla leaves function as inocula for the new plant generations. Using electron microscopy and immunogold-labeling, the fate of the cyanobacterium during colonization and development of the megasporocarp was revealed. On entering the indusium chamber of the megasporocarps as small-celled motile cyanobacterial filaments (hormogonia), these differentiated into large thick-walled akinetes (spores) in a synchronized manner. This process was accompanied by cytoplasmic reorganizations and the release of numerous membrane vesicles, most of which contained DNA, and the formation of a highly structured biofilm. Taken together the data revealed complex adaptations in the cyanobacterium during its transition between plant generations.
[1] To improve understanding and capture the direct evidence of the impact of dust aerosol on climate, the 2008 China-U.S. joint field campaigns are conducted. Three sites are involved this campaign, including one permanent site (Semi-Arid Climate and Environment Observatory of Lanzhou University (SACOL)) (located in Yuzhong, 35.95°N, 104.1°E), one SACOL's Mobile Facility (SMF) (deployed in Jintai, 37.57°N, 104.23°E), and the U.S. Department of Energy Atmospheric Radiation Measurements (ARM) Ancillary Facility (AAF mobile laboratories, SMART-COMMIT) (deployed in Zhangye, 39.08°N, 100.27°E). This paper presents the results of direct measurement analysis of the dust plume transport case. During the dust plume period, the OMI AI data and air mass back trajectory model (HYSPLIT) clearly illustrated that the air mass originated from the Taklamakan desert and Inner Mongolia Gobi desert. The daily averaged concentrations of PM 10 were about 0.2 ± 0.03 mg/m 3 at SACOL and Zhangye, but during the dust plume the mass concentration of dust aerosol were 0.98 mg/m 3 at Zhangye and 0.52 mg/m 3 at SACOL. The black carbon (BC) value reached its high peak during the dust plume. However, the concentration of BC was not only fluctuated with the dust plume, but also affected by the local air pollutants. When the dust plume occurred, the multiwavelength aerosol optical depth can be raised to ∼2, ∼1.5 times as high as that during the non dust plume period, and the number (mass) distribution during the dust plume showed the aerosol types considered correspond to urban/industrial aerosols, coarse mode particles. The meteorological analysis indicated that these polluted layers are not only transported from their sources, but also include the local sources.
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