RESUMEN

Coordinated cochaperone interactions with Hsp90 and associated client proteins are crucial for a multitude of signaling pathways in normal physiology, as well as in disease settings. Research on the molecular mechanisms regulated by the Hsp90 multiprotein complexes has demonstrated increasingly diverse roles for cochaperones throughout Hsp90-regulated signaling pathways. Thus, the Hsp90-associated cochaperones have emerged as attractive therapeutic targets in a wide variety of disease settings. The tetratricopeptide repeat (TPR)-domain immunophilins FKBP51 and FKBP52 are of special interest among the Hsp90-associated cochaperones given their Hsp90 client protein specificity, ubiquitous expression across tissues, and their increasingly important roles in neuronal signaling, intracellular calcium release, peptide bond isomerization, viral replication, steroid hormone receptor function, and cell proliferation to name a few. This review summarizes the current knowledge of the structure and molecular functions of TPR-domain immunophilins FKBP51 and FKBP52, recent findings implicating these immunophilins in disease, and the therapeutic potential of targeting FKBP51 and FKBP52 for the treatment of disease.

RESUMEN

This data article provide results of the studies conducted to develop a mesoporous silica coated Gd2.98Ce0.02Al5O12 nanoparticles loaded with a photosensitizer dye rose Bengal (RB) system (GAG@mSiO2@RB) capable of producing reactive oxygen species (ROS) upon exposure to blue light. The data reported here is related with Jain et al. (2018) [1]. It contains histogram of particle size distribution, cathodoluminescence (CL), photoluminescence spectra and there spectral overlap with the absorption spectra of RB, a graph showing the loading percentage of RB at different concentrations. Moreover, the data indicating ROS generation evaluated using 1,2-diphenylisobenzofuran (DPBF) assay and the viability of MDA-MB-231 cells upon exposure with different concentration of GAG@mSiO2 nanoparticles, upon exposure with blue light is also included in the data.

RESUMEN

Nanoparticle (NP) and photosensitizer (PS) conjugates capable of X-ray photodynamic therapy (X-PDT) are a research focus due to their potential applications in cancer treatment. Combined with X-PDT, appropriate imaging properties of the nanocomposite will make it suitable for theranostics of deep lying tumors. In this work, we describe the development of magnetic-luminescent Gd2.98Ce0.02Al5O12 nanoparticles (GAG) coated with mesoporous silica (mSiO2) and loaded with rose bengal (RB) to yield a nanocomposite GAG@mSiO2@RB capable of X-PDT. GAG nanoparticles were synthesized using the sol-gel method. The synthesized GAG nanoparticles showed a strong visible yellow emission with a quantum yield of ∼32%. Moreover, the broad emission spectra of GAG nanoparticles centered at 585 nm showed a good overlap with the absorption of RB. Upon irradiation with X-rays (55 KV), the GAG@mSiO2@RB nanocomposite produced significantly higher singlet oxygen compared with RB alone, as confirmed by the 1,2-diphenylisobenzofuran (DPBF) assay. The developed GAG@mSiO2@RB nanocomposite significantly reduced the viability of human breast cancer (MDA-MB-231) cells upon irradiation with blue light (λ = 470 nm). The calculated LC50 of GAG@mSiO2@RB nanocomposites were 26.69, 11.2, and 6.56 µg/mL at a dose of ∼0.16, 0.33 and 0.5 J/cm2, respectively. Moreover, the nanocomposite showed paramagnetic properties with high magnetic mass susceptibility which are useful for high contrast T1 weighted magnetic resonance imaging (MRI). Together with X-PDT, the paramagnetic properties of the proposed GAG@mSiO2@RB nanocomposite system are promising for their future application in simultaneous detection and treatment of deep-lying tumors.

Asunto(s)

RESUMEN

The plant originated stilbene "resveratrol" (3,4',5-trans-trihydroxystilbene) is well known for its diverse health benefits including anti-tumor, anti-inflammatory, anti-microbial, and anti-oxidant properties. Besides a significant amount of reports on different aspects of its application as prodrug in the last 50 years, still, a strategy leading to the production of the active drug is missing. The aim of this work was to evaluate the enzymatic activation of prodrug resveratrol to the effective drug piceatannol, without engaging expensive cofactors. Five different heme proteins were analyzed for the transformation of resveratrol. Kinetic parameters of resveratrol transformation and analysis of the transformed products were conducted through HPLC and GC-MS. Effect of pH and organic solvent on the transformation process had also been evaluated. Among all tested heme proteins, only a variant of cytochrome P450BM3 from Bacillus megaterium (CYPBM3F87A) was found suitable for piceatannol production. The most suitable pH for the reaction conditions was 8.5, while organic solvents did not show any effect on transformation. For resveratrol transformation, the turnover rate (k cat) was 21.7 (± 0.6) min-1, the affinity constant (K M) showed a value of 55.7 (± 16.7) µM for a catalytic efficiency (k cat/K M) of 389 min-1 mM-1. GC-MS analysis showed that the only product from resveratrol transformation by cytochrome P450BM3 is the biologically active piceatannol. The enzymatic transformation of resveratrol, an emerging compound with medical interest, to active product piceatannol by a variant of cytochrome P450BM3 in the absence of expensive NADPH cofactor is demonstrated. This enzymatic process is economically attractive and can be scaled up to cover the increasing medical demand for piceatannol.

Asunto(s)

RESUMEN

Chitosan, a renewable biopolymer has the prospective applications in different fields due to its gelation capacity. Nanoconfiguration of chitosan through ionotropic gelation to encapsulate enzymatic activity offers numerous potential applications. In the present study, the preparation and characterization of chitosan nanoparticles loaded with versatile peroxidase are reported. Their performance in bioremediation process and the resistance enhancement against natural microbial biodegradation were studied. The average diameter of enzymatic nanoparticles was 120nm and showed a high enzyme loading capacity. The kinetic parameters of nanoparticles exhibited a slightly lower catalytic activity (kcat), similar affinity constant (Km) for hydrogen peroxide and higher Km value for the phenolic compound when compared with the free enzyme. The enzymatic nanoparticles showed higher thermostability and the same pH activity profile than those from free enzyme. Ten phenolic compounds, including pesticides, halogenated compounds, endocrine disruptors and antibacterials were transformed by the enzymatic nanoparticles. The transformation rate was lower than those obtained with free enzyme suggesting mass transfer limitations. But very importantly, the enzymatic nanoparticles showed a significant increase of the operational stability in real conditions of wastewater treatment process. Moreover, chemical modification of nanoparticles with different aldehydes still enhanced the operational stability of nanoparticulated enzymes. This enhancement of stability in real conditions and the potential use of biocatalytic nanoparticles in bioremediation processes are discussed.

Asunto(s)

RESUMEN

A novel concept with the result of enzyme stabilization against microbial degradation in real bioremediation processes was developed through the encapsulation of laccase in chitosan nanoparticles. Besides of abundant information on laccase-chitosan conjugates, we report the laccase encapsulation into nanoparticles based in chitosan. The chitosan-tripolyphosphate technique was applied for the production of morphologically homogeneous enzymatic nanoparticles, with high enzyme encapsulation efficiency, small asymmetric sizes (from 40 to 90 nm), and rough surfaces. Contrary to macroscopic immobilized enzymes, temperature and pH activity profiles of nano-sized laccase were similar to those of free enzyme. The substrate affinity constant (K M) of nano-encapsulated laccase was similar to these from free enzyme, while its activity rate constant (k cat) represented 60 % of these obtained with free enzyme. Importantly, stability of nano-encapsulated laccase against microbial degradation in soil, compost, and wastewater was significantly increased. After 24 h exposure to wastewater from a treatment plant, the laccase activity of the nanoparticles was 82.8 % of initial activity, compared with only 7.8 % retained activity for free enzyme. After 36 h incubation in compost extract, the laccase nanoparticles showed 72.4 % of the initial activity, while the free enzyme was almost completely inactivated. Finally, after 84 h incubation in soil extract, the nanoparticles and free preparations showed 57.9 and 17.3 % of the initial activity, respectively. Thus, the nanoencapsulation of enzymes able to transform pollutants is an alternative to improve the operational lifetime of enzymes in real environmental applications.

Asunto(s)

RESUMEN

A potent fungus for amylase production, Chrysosporium asperatum, was isolated from among 30 different cultures obtained from wood samples collected in the Junagadh forest, India. All of the isolated cultures were screened for their ability to produce amylase by submerged fermentation. Among the selected cultures, C. asperatum (Class Euascomycetes; Onygenales; Onygenaceae) gave maximum amylase production. In all of the different media tested, potato starch was found to be a good substrate for production of amylase enzyme at 30 degrees C and pH 5.0. Production of enzyme reached the maximum when a combination of starch and 2% xylose, and organic nitrogen (1% yeast extract) and ammonium sulfate were used as carbon and nitrogen sources, respectively. There was no significant effect of metal ions on enzyme activity. The enzyme was relatively stable at 50 degrees C for 20 min, and no inhibitory effect of Ca+2 ions on amylase production was observed.

Asunto(s)

RESUMEN

Morpho-anatomical features in leaves, stems and unripe fruits of Solanum pseudocapsicum L., Solanaceae, were investigated by histological methods. Anatomically the plant may be characterised by the presence of uniseriate trichomes, anomocytic stomata, calcium oxalate needles in leaves while presence of oval to circular compound starch grains, angular vessels, vertically upright, uni-biseriate rays and intraxylary phloem with differentiation of internal cambium abutting marginal pith cells and protoxylem in transverse view. Development of distinct internal cambium may be considered as a characteristic feature for S. pseudocapsicum. Intraxylary secondary phloem was composed of sieve tube elements, companion cells and axial parenchyma cells.