Skinnerfraser3619
Depression is apparently the most common psychiatric disease among the mood disorders affecting about 10% of the adult population. The etiology and pathogenesis of depression are still poorly understood. https://www.selleckchem.com/products/rocilinostat-acy-1215.html Hence, as for most human diseases, animal models can help us understand the pathogenesis of depression and, more importantly, may facilitate the search for therapy. In this review we first describe the more common tests used for the evaluation of depressive-like symptoms in rodents. Then we describe different models of depression and discuss their strengths and weaknesses. These models can be divided into several categories genetic models, models induced by mental acute and chronic stressful situations caused by environmental manipulations (i.e., learned helplessness in rats/mice), models induced by changes in brain neuro-transmitters or by specific brain injuries and models induced by pharmacological tools. In spite of the fact that none of the models completely resembles human depression, most animal models are relevant since they mimic many of the features observed in the human situation and may serve as a powerful tool for the study of the etiology, pathogenesis and treatment of depression, especially since only few patients respond to acute treatment. Relevance increases by the fact that human depression also has different facets and many possible etiologies and therapies.In this work, we aimed to develop a hybrid theranostic nano-formulation based on gold nanoparticles (AuNP)-having a known anti-angiogenic character-and the angiogenin (ANG), in order to tune the angiogenesis-related phases involved in the multifaceted process of the wound healing. To this purpose, spherical were surface "decorated" with three variants of the protein, namely, the recombinant (rANG), the wild-type, physiologically present in the human plasma (wtANG) and a new mutant with a cysteine substitution of the serine at the residue 28 (S28CANG). The hybrid biointerface between AuNP and ANG was scrutinized by a multi-technique approach based on dynamic light scattering, spectroscopic (UV-visible, circular dichroism) and microscopic (atomic force and laser scanning confocal) techniques. The analyses of optical features of plasmonic gold nanoparticles allowed for discrimination of different adsorption modes-i.e.; predominant physisorption and/or chemisorption-triggered by the ANG primary sequence. Biophysical experiments with supported lipid bilayers (SLB), an artificial model of cell membrane, were performed by means of quartz crystal microbalance with dissipation monitoring acoustic sensing technique. Cellular experiments on human umbilical vein endothelial cells (HUVEC), in the absence or presence of copper-another co-player of angiogenesis-were carried out to assay the nanotoxicity of the hybrid protein-gold nanoassemblies as well as their effect on cell migration and tubulogenesis. Results pointed to the promising potential of these nanoplatforms, especially the new hybrid Au-S28CANG obtained with the covalent grafting of the mutant on the gold surface, for the modulation of angiogenesis processes in wound care.
Cyclin-dependent kinases (CDKs) regulate mammalian cell cycle progression and RNA transcription. Based on the structural analysis of previously reported CDK2 inhibitors, a new compound with 3-hydrazonoindolin-2-one scaffold (
) was well designed, synthesized, and biologically evaluated as a promising anti-breast cancer hit compound.
The potential anti-cancerous effect of
was evaluated using cytotoxicity assay, flow cytometric analysis of apoptosis and cell cycle distribution, ELISA immunoassay, in vitro CDK2/cyclin A2 activity, and molecular operating environment (MOE) virtual docking studies.
The results revealed that
exhibits pronounced CDK2 inhibitory activity and cytotoxicity in human breast cancer MCF-7 cell line. The cytotoxicity of
was found to be intrinsically mediated apoptosis, which in turn, is associated with low Bcl-2 expression and high activation of caspase 3 and p53. Besides,
blocked the proliferation of the MCF-7 cell line and arrested the cell cycle at the G2/M phase. The docking studies did not confirm which one of geometric isomers (
and
) is responsible for binding affinity and intrinsic activity of
. However, the molecular dynamic studies have confirmed that the
-isomer has more favorable binding interaction and thus is responsible for CDK2 inhibitory activity.
These findings displayed a substantial basis of synthesizing further derivatives based on the 3-hydrazonoindolin-2-one scaffold for favorable targeting of breast cancer.
These findings displayed a substantial basis of synthesizing further derivatives based on the 3-hydrazonoindolin-2-one scaffold for favorable targeting of breast cancer.The photocatalyst materials correlation with the radiation scenario and pollutant molecules can have a significant influence on the overall photocatalytic efficiency. This work aims to outline the significance of optimizing the components mass ratio into a tandem structure in order to increase the photocatalytic activity toward pollutant removal. ZnO_SnO2 and TiO2_SnO2 tandem structures were obtained by the doctor blade technique using different mass ratios between the components. The samples contain metal oxides with crystalline structures and the morphology is influenced by the main component. The photocatalytic activity was tested using three radiation scenarios (UV, UV-Vis, and Vis) and two pollutant molecules (tartrazine and acetamiprid). The results indicate that the photocatalytic activity of the tandem structures is influenced by the radiation wavelength and pollutant molecule. The TiO2_SnO2 exhibit 90% photocatalytic efficiency under UV radiation in the presence of tartrazine, while ZnO_SnO2 exhibit 73% photocatalytic efficiency in the same experimental conditions. The kinetic evaluation indicate that ZnO_SnO2 (21) have a higher reaction rate comparing with TiO2_SnO2 (12) under UV radiation in the presence of acetamiprid.Avian coronavirus infectious bronchitis virus (IBV) causes severe economic losses in the poultry industry, but its control is hampered by the continuous emergence of new genotypes and the lack of cross-protection among different IBV genotypes. We designed a new immunogen based on a spike with the consensus nucleotide sequence (S_con) that may overcome the extraordinary genetic diversity of IBV. S_con was cloned into a pVAX1 vector to form a new IBV DNA vaccine, pV-S_con. pV-S_con could be correctly expressed in HD11 cells with corresponding post-translational modification, and induced a neutralizing antibody response to the Vero-cell-adapted IBV strain Beaudette (p65) in mice. To further evaluate its immunogenicity, specific-pathogen-free (SPF) chickens were immunized with the pV-S_con plasmid and compared with the control pVAX1 vector and the H120 vaccine. Detection of IBV-specific antibodies and cell cytokines (IL-4 and IFN-γ) indicated that vaccination with pV-S_con efficiently induced both humoral and cellular immune responses.
