Speciation Studies of Bifunctional 3-Hydroxy-4-Pyridinone Ligands in the Presence of Zn2+ at Different Ionic Strengths and Temperatures

The acid-base properties of two bifunctional 3-hydroxy-4-pyridinone ligands and their chelating capacity towards Zn2+, an essential bio-metal cation, were investigated in NaCl aqueous solutions by potentiometric, UV-Vis spectrophotometric, and 1H NMR spectroscopic titrations, carried out at 0.15 ≤ I/mol -1 ≤ 1.00 and 288.15 ≤ T/K ≤ 310.15. A study at I = 0.15 mol L-1 and T = 298.15 K was also performed for other three Zn2+/Lz- systems, with ligands belonging to the same family of compounds. The processing of experimental data allowed the determination of protonation and stability constants, which showed accordance with the data obtained from the different analytical techniques used, and with those reported in the literature for the same class of compounds. ESI-MS spectrometric measurements provided support for the formation of the different Zn2+/ligand species, while computational molecular simulations allowed information to be gained on the metal-ligand coordination. The dependence on ionic strength and the temperature of equilibrium constants were investigated by means of the extended Debye-Hückel model, the classical specific ion interaction theory, and the van't Hoff equations, respectively

Improvement of Gait after Robotic-Assisted Training in Children with Cerebral Palsy: Are We Heading in the Right Direction?

Cerebral palsy (CP) is a non-progressive congenital neurological disorder that affects different physical and cognitive functions in children. In addition to standard rehabilitation, advanced robotic gait devices are novel tools that are becoming progressively more common as part of the treatment of CP. The aim of this study is to evaluate the effects of Lokomat training, in addition to conventional rehabilitation, on the motor function and quality of life of children with ataxic-spastic CP (ASCP). Ten children with ASCP who attended the Robotic Rehabilitation OutClinic of the IRCCS Centro Neurolesi “Bonino Pulejo”, from April to June 2019, were enrolled in this study. They received twenty-four robotic rehabilitation sessions, twice a week for three months, each session lasting about 45 min. They were also provided with conventional physical and occupational therapy. After the innovative training, we found significant changes in the children’s outcomes, i.e., in GMFM (p < 0.001), with significant improvements in sitting (p < 0.03) and walking (p < 0.03). Moreover, the quality of life of the young patients, evaluated by their parents, significantly improved (p < 0.005). The use of robotic systems could be considered to be an effective complementary treatment to improve gait, as well as quality of life, in children with CP

Small molecule regulators of microRNAs identified by high-throughput screen coupled with high-throughput sequencing

Abstract MicroRNAs (miRNAs) regulate fundamental biological processes by silencing mRNA targets and are dysregulated in many diseases. Therefore, miRNA replacement or inhibition can be harnessed as potential therapeutics. However, existing strategies for miRNA modulation using oligonucleotides and gene therapies are challenging, especially for neurological diseases, and none have yet gained clinical approval. We explore a different approach by screening a biodiverse library of small molecule compounds for their ability to modulate hundreds of miRNAs in human induced pluripotent stem cell-derived neurons. We demonstrate the utility of the screen by identifying cardiac glycosides as potent inducers of miR-132, a key neuroprotective miRNA downregulated in Alzheimer’s disease and other tauopathies. Coordinately, cardiac glycosides downregulate known miR-132 targets, including Tau, and protect rodent and human neurons against various toxic insults. More generally, our dataset of 1370 drug-like compounds and their effects on the miRNome provides a valuable resource for further miRNA-based drug discovery