Heat shock protein 27 (Hsp-27) encoded by gene HSPB1 is a critical regulator of the behavioral phenotype of human prostate cancer (PCa) cells, enhanced expression being associated with highly ...aggressive disease and poor clinical outcome. In contrast, the protein is not expressed in PCas of low malignant potential. To gain insight into the mechanism regulating its expression, we tested the hypothesis that differential methylation of CpG islands within HSPB1 controls transcription and subsequent translation of the gene.
We studied prostate epithelial cell lines and tissue biopsies, including 59 BPH and 415 PCas, of which 367 were a cohort of men with up to 20 years of follow-up. Methylation across the gene (DNA methylation (DNAme)) was assayed by pyrosequencing. Hsp-27 expression was assessed by western blot and immunohistochemistry.
In cancer tissues, methylation increased in a 3' direction (P < 0.0001) whereas in benign hyperplasia methylation was constantly below 5%, a cutoff giving a specificity of 100% and sensitivity of 50%. Although methylation of the promoter region was significantly discriminating between benign and malignant prostatic epithelia, it compared poorly with methylation of the first intron. The prognostic value of HSPB1 DNAme was confirmed by both univariate (hazard ratio 1.77 per 50% increment, P = 0.02) and multivariate models. Interaction between HSPB1 methylation and Gleason score revealed high DNAme to be a reliable prognostic marker of poor outcome in men with low Gleason score (P = 0.014).
Our data indicate CpG methylation of the first HSPB1 intron to be an important biomarker that identifies aggressive PCas otherwise regarded as low risk by current clinical criteria but that, biologically, require immediate active management.
In the present work, Co1−xMnxFe2O4 nanoparticles were synthesized by the low-temperature auto-combustion method. The thermal decomposition process was investigated by means of differential and ...thermal gravimetric analysis (TG-DTA) that showed the precursor yield the final product above 450°C. The phase purity and crystal lattice symmetry were estimated from X-ray diffraction (XRD). Microstructural features observed by scanning electron microscopy (SEM) demonstrates that the fine clustered particles were formed with an increase in average grain size with Mn2+ content. Fourier transform infrared spectroscopy (FTIR) study confirms the formation of spinel ferrite. Room temperature magnetization measurements showed that the magnetization Ms increases from 29 to 60emu/g and Hc increases from 13 to 28Oe with increase in Mn2+ content, which implies that these materials may be applicable for magnetic data storage and recording media.
•Low temperature auto combustion synthesis of Co–Mn nanoparticles.•Magneto-structural properties of Co–Mn ferrite nanoparticles.•Use for magnetic recording and data storage.
► Polyvinyl alcohol coating does not affect on structural properties of magnetic nanoparticles. ► Monodisperse characteristics and biocompatibility can be achieved with biocompatible polymer coating ...on the surface of magnetic nanoparticles. ► Surface properties of magnetic nanoparticles can be manipulate with polymer coatings.
In the present work, cobalt ferrite nanoparticles (CoFe2O4 NPs) have been synthesized by combustion method. The surface of the CoFe2O4 NPs was modified with biocompatible polyvinyl alcohol (PVA). To investigate effect and nature of coating on the surface of CoFe2O4 NPs, the NPs were characterized X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and thermogravimetric analysis (TGA). The transmission electron microscopy (TEM) and dynamic light scattering (DLS) results demonstrate the monodispersed characteristics of CoFe2O4 NPs after surface modification with PVA. The decrease in contact angle from 162° to 50° with PVA coating on NPs indicates the transition from hydrophobic nature to hydrophilic. The Magnetic properties measurement system (MPMS) results show that the NPs have ferromagnetic behavior with high magnetization of 75.04 and 71.02emu/g of uncoated and coated CoFe2O4 NPs respectively. These PVA coated NPs exhibit less toxicity over uncoated CoFe2O4 NPs up to 1.8mgmL−1 when tested with mouse fibroblast L929 cell line.
Nanocrystals of magnetite (Fe3O4) were prepared by alkaline precipitation. The precursor used for synthesis was ferrous chloride only and the reaction was carried out in absence of any oxidant. The ...synthesized pure phase magnetic nanoparticles (MNPs) were coated with a biocompatible polymer, chitosan (CS). FTIR and TGA confirm coating of CS on MNPs. Both bare and coated MNPs (Fe3O4 and CS-Fe3O4) show particle size 21.8 plus or minus 5.3 and 15.1 plus or minus 5.0nm respectively. The magnetization values of both the MNPs are 51.68 and 49.96emu/g at room temperature respectively. Negligible Coercivity and Remenance values at room temperature imply superparamagnetic behavior of the MNPs. The MNPs are studied for their induction heating abilities at 167.6, 251.4 and 335.2Oe (equivalent to 13.3, 20.0 and 26.7kAm-1 respectively), in order to use them in magnetic fluid hyperthermia therapy. At 335.2Oe, CS coated nanoparticles (NPs) show maximum SAR of 118.85W/g, while bare NPs show SAR of 79.32W/g. Low cytotoxic effects of both the MNPs on L929 cell line proved their suitability for in vivo applications. --NH2 group rendered by CS can further be used for conjugation of biomolecules to make them suitable candidates for biosensing and targeted drug delivery.
UV, HPLC and HPTLC methods were developed and validated for the quantitative determination of Pirfenidone, a novel antifibrotic agent used in idiopathic pulmonary fibrosis. Chromatography was carried ...out by isocratic technique on reversed phase Eclipse XDB-C18 column (150 x 4.6 mm, 5 μm) with mobile phase consisting of phosphate buff acetonitrile (pH 3.5) 72:28 v/v at flow rate 1 mL/min. TLC was carried out by stationary phase precoated Silica Gel 60 F254 TLC Plate using mobile phase Toluene: Methanol, 8:2 v/v. The UV spectrophotometric determination was performed at 311 nm using solvent methanol. The proposed methods were validated according to ICH Q2-(R1) guidelines. The linearity range for Pirfenidone was 5-70 μg/mL for HPLC, 800-1600 ng/spot for HPTLC and 10-60 μg/mL for UV method. These methods were accurate and precise with recoveries in the range of 98.2-102.32 and relative standard deviation < 2%. The developed methods were successfully applied for determination of Pirfenidone in tablets.
We report a significant spectral drift (up to 110 nm) between optical scattering and extinction in magnetite-gold (Fe 3 O 4 -Au) core–shell nanostructures. The drift was observed experimentally using ...single-particle broadband dark-field scattering microspectroscopy and solution extinction experiments. Infrared thermography demonstrates an enhanced photothermal activity of these nanoparticles at extinction wavelengths that are far drifted from the wavelengths that produce the best results for imaging via scattering. For example, a relatively smooth gold shell leads to 19% more photothermal activity at 532 nm compared to 690 nm whereas a rough-texture, popcorn type morphology gold shell with three times higher drift, is 170% more efficient at 532 nm. We suggest that the enhanced photothermal response results directly from a reduced competition between absorption and scattering as a consequence of the spectral drift. This spectral drift can be advantageous in multimodal theranostics where therapy and imaging are performed independently at different wavelengths.
We report a significant spectral drift (up to 110 nm) between optical scattering and extinction in magnetite-gold (Fe
3
O
4
-Au) core-shell nanostructures. The drift was observed experimentally using ...single-particle broadband dark-field scattering microspectroscopy and solution extinction experiments. Infrared thermography demonstrates an enhanced photothermal activity of these nanoparticles at extinction wavelengths that are far drifted from the wavelengths that produce the best results for imaging
via
scattering. For example, a relatively smooth gold shell leads to 19% more photothermal activity at 532 nm compared to 690 nm whereas a rough-texture, popcorn type morphology gold shell with three times higher drift, is 170% more efficient at 532 nm. We suggest that the enhanced photothermal response results directly from a reduced competition between absorption and scattering as a consequence of the spectral drift. This spectral drift can be advantageous in multimodal theranostics where therapy and imaging are performed independently at different wavelengths.
Optical studies of magnetite-gold, core-shell nanostructures reveal a spectral drift between the scattering and extinction, accompanied by interesting photothermal effects.
Summary Prostate cancer is a common malignancy in men and the worldwide burden of this disease is rising. Lifestyle modifications such as smoking cessation, exercise, and weight control offer ...opportunities to reduce the risk of developing prostate cancer. Early detection of prostate cancer by prostate-specific antigen (PSA) screening is controversial, but changes in the PSA threshold, frequency of screening, and the use of other biomarkers have the potential to minimise the overdiagnosis associated with PSA screening. Several new biomarkers for individuals with raised PSA concentrations or those diagnosed with prostate cancer are likely to identify individuals who can be spared aggressive treatment. Several pharmacological agents such as 5α-reductase inhibitors and aspirin could prevent development of prostate cancer. In this Review, we discuss the present evidence and research questions regarding prevention, early detection of prostate cancer, and management of men either at high risk of prostate cancer or diagnosed with low-grade prostate cancer.
We present MeerKAT 1000 MHz and 1400 MHz observations of a bright radio galaxy in the southern hemisphere, ESO 137-006. The galaxy lies at the centre of the massive and merging Norma galaxy cluster. ...The MeerKAT continuum images (rms ∼0.02 mJy beam
−1
at ∼10″ resolution) reveal new features that have never been seen in a radio galaxy before: collimated synchrotron threads of yet unknown origin, which link the extended and bent radio lobes of ESO 137-006. The most prominent of these threads stretches in projection for about 80 kpc and is about 1 kpc in width. The radio spectrum of the threads is steep, with a spectral index of up to
α
≃ 2 between 1000 and 1400 MHz.
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