Zobrazení zdroje stránky Abildgaardmacmillan4481

The aim of this study to investigate the effects of melamine exposure from the weaning period on the developing brain in rats. Female Wistar albino rats (21 days old, n = 18) were divided into 3 groups, all animals were weighed daily and dose-adjusted. For 3 weeks, 0.1 mL of saline was administered by oral gavage to the control group, 50 mg/kg of melamine to the second group, and 75 mg/kg of melamine to the third group were administered by oral gavage by dissolving in 0.1 mL of saline. On the postnatal 45th day, the rats were sacrificed under anesthesia and brain tissues placed in neutral formalin. After routine tissue processing, brain sections were stained with hematoxylin&amp;eosin(H&amp;E) and Terminal deoxynucleotidyl transferase(TdT) dUTP Nick-End Labeling(TUNEL), IBA-1, Glial Fibrillar Acidic Protein(GFAP), Tumor necrosis factor-α (TNF-α), and SMI-70 antibodies as immunohistochemically. In the results, according to apoptotic index(AI) results, there was a significant increase in the 75 mg/kg and 50 mg/kg melamine groups compared to the control groups (p  005). Melamine exposure (50 mg/kg and 75 mg/kg) from the weaning period causes apoptosis and inflammation in the developing brain, and the disruptions in the blood-brain barrier (BBB) significantly increase exposure to 75 mg/kg.Inhibition of an imperative antioxidant enzyme with subsequent death is a victorious and widely accepted strategy to combat various infectious diseases. Among different antioxidant enzymes, thioredoxin reductase (TrxR) is an exclusive one. Studies have revealed that direct inhibition of TrxR by different classes of chemical moieties promptly results in the death of an organism. Especially the structural as well as biochemical modifications of the enzyme upon inhibition project serious threat towards the subject organism. Herein, an attempt was made to inhibit TrxR of filarial species by administering Auranofin, 1 chloro 2,4 dinitrobenzene (CDNB), Curcumin, and a novel carbamo dithioperoxo(thioate) derivative (4a). Our study has revealed that inhibition of TrxR resulted in the induction of the classical CED pathway of apoptosis along with the intrinsic and extrinsic pathways of apoptosis (Caspase mediated) routed through the ASK-1/p38 axis. Druggability analysis of filarial TrxR for the selected compounds was performed in silico through molecular docking studies. Therefore, this study attempts to decipher the mechanism of apoptosis induction following TrxR inhibition. [https://www.selleckchem.com/products/phosphoenolpyruvic-acid-monopotassium-salt.html Selleckchem Phospho(enol)pyruvic acid monopotassium] The safety of those four compounds in terms of dose and toxicity was taken under consideration. Thitherto, the mechanism of TrxR mediated initiation of cell death in filarial parasite has remained undercover, and therefore, it is a maiden report on the characterization of apoptosis induction upon TrxR inhibition which will eventually help in generating effective antifilarial drugs in the future.The poor printability of most pharmaceutical polymers greatly restricts the application of the fused deposition modeling (FDM) technique in the field of personalized pharmaceutical preparations. General strategies to improve printability and provide practical guidelines for the optimization of formulations are lacking. Moreover, the mechanism associated with the smooth printing process of modified printing materials needs to be investigated. In this study, three different strategies were used to improve the FDM printability of typical brittle polymers with poor printability. The relationship among additives, material properties, and printability was explored. The finite element method was used to simulate the radial stress-strain behavior of the filament, while computational fluid dynamics was used to simulate the axial melt flow field in the printing head. It was found that the addition of an inert filler (i.e., talc), a drug with high melting points (i.e., diclofenac sodium), and a polymer with high strength (i.e., plasticized ethylcellulose) effectively improved the printability of plasticized Eudragit® EPO and Soluplus®. In addition, regulating the mechanical properties of filaments improved printability, and it was deduced that printable filaments should have neither very low stiffness nor very low flexibility. The suitable melt viscosity or shear-thinning property of the printing material facilitated smooth extrusion without filament breakage or nozzle blockage. The results of this study also showed that simulation could assist in understanding the stress-strain behavior of filaments and the flow field of melts during FDM printing.Lipid nanoparticles (LNPs) are increasingly employed to improve delivery efficiency and therapeutic efficacy of nucleic acids. Various formulation parameters can affect the quality attributes of these nanoparticle formulations, but currently there is a lack of systemic screening approaches to address this challenge. Here, we developed an automated high-throughput screening (HTS) workflow for streamline preparation and analytical characterization of LNPs loaded with antisense oligonucleotides (ASOs) in a full 96-well plate within 3 hrs. ASO-loaded LNPs were formulated by an automated solvent-injection method using a robotic liquid handler, and assessed for particle size distribution, encapsulation efficiency, and stability with different formulation compositions and ASO loadings. Results indicated that the PEGylated lipid content significantly affected the particle size distribution, while the ionizable lipid / ASO charge ratio impacted the encapsulation efficiency of ASOs. Furthermore, results from our HTS approach correlated with those from the state-of-the-art scale-up method using a microfluidic formulator, therefore opening up a new avenue for robust formulation development and design of experiment methods, while reducing material usage by 10 folds, improving analytical outputs and accumulation of information by 100 folds.<br /><br /> Iodine-131 labeled hypericin (<br /><br /> I-Hyp) has been utilized as a necrosis-avid theragnostic tracer in a dual targeting pan-anticancer strategy called OncoCiDia. Widespread use of previously-tested solvent dimethyl sulfoxide (DMSO) is limited by safety concerns. To tackle this, the present study was designed to explore a clinically feasible excipient for the formulation of the hydrophobic <br /><br /> I-Hyp for intravenous administration.<br /><br /> Solubility of Hyp in serial solutions of already-approved hydroxypropyl-β-cyclodextrin (HP-β-CD) was evaluated by UVspectrophotometry and 50% HP-β-CD was chosen for further experiments. Two novel HP-β-CD-based formulations of <br /><br /> I-Hyp were compared with previous DMSO-based formulation, with regards to necrosis-targetability and biodistribution, by magnetic resonance imaging, single-photon emission computed tomography (SPECT), gamma counting, autoradiography, fluorescence microscopy and histopathology.<br /><br /> Hyp solubility was enhanced with increasing HP-β-CD concentrations. The radiochemical purity of <br /><br /> I-Hyp was higher than 90% in all formulations.