Finite Element Modeling Application in Forensic Practice: A Periprosthetic Femoral Fracture Case Study

The incidence of periprosthetic fractures has rapidly increased in the last two decades and has been the cause of a large number of revision surgeries and permanent physical disability for many patients, as well as a significant socioeconomic burden for many nations. This research deals with a periprosthetic femur fracture real event, occurred following a total hip arthroplasty and treated with one of the most widespread internal fixation methods: the implant of a periprosthetic femur plate system. A Finite Element analysis was performed to investigate the implanted femur plate break after a short follow-up and to understand the plate break causes. Such events are currently object of forensic debate as more and more often hospitals, surgeons, and medical device manufacturers are denounced by patients to whom similar events occur. In this work, different load situations acting on the femur during daily and incidental activities were simulated, in order to validate the correct behavior of the plate, according to the intended use recommended by the manufacturer. The analysis demonstrates that the plate failure can occur in situations of unconventional loading such as that caused by stumbling and in presence of incomplete bone healing

Investigation on the ZBG-functionality of phenyl-4-yl-acrylohydroxamic acid derivatives as histone deacetylase inhibitors

A series of alternative Zn-binding groups were explored in the design of phenyl-4-yl-acrylohydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors. Most of the synthesized compounds were less effective than the parent hydroxamic acid. However, the profile of activity shown by the analog bearing a hydroxyurea head group, makes this derivative promising for further investigation

Biphenyl-4-yl-acrylohydroxamic acids: identification of a novel indolyl-substituted HDAC inhibitor with antitumor activity

Modification of the cap group of biphenylacrylohydroxamic acid-based HDAC inhibitors led to the identification of a new derivative (3) characterized by an indolyl-substituted 4-phenylcinnamic skeleton. Molecular docking was used to predict the optimal conformation in the class I HDACs active site. Compound 3 showed HDAC inhibitory activity and antiproliferative activity against a panel of tumor cell lines, in the low \u3bcM range. The compound was further tested in vitro for acetylation of histone H4 and other non-histone proteins, and in vivo in a colon carcinoma model, showing significant proapoptotic and antitumor activities

Structure-Based Design and Optimization of Multitarget-Directed 2H-Chromen-2-one Derivatives as Potent Inhibitors of Monoamine Oxidase B and Cholinesterases

The multifactorial nature of Alzheimer’s disease calls for the development of multitarget agents addressing key pathogenic processes. To this end, by following a docking-assisted hybridization strategy, a number of aminocoumarins were designed, prepared, and tested as monoamine oxidases (MAOs) and acetyl- and butyryl-cholinesterase (AChE and BChE) inhibitors. Highly flexible N-benzyl-N-alkyloxy coumarins 2–12 showed good inhibitory activities at MAO-B, AChE, and BChE but low selectivity. More rigid inhibitors, bearing meta- and para-xylyl linkers, displayed good inhibitory activities and high MAO-B selectivity. Compounds 21, 24, 37, and 39, the last two featuring an improved hydrophilic/lipophilic balance, exhibited excellent activity profiles with nanomolar inhibitory potency toward hMAO-B, high hMAO-B over hMAO-A selectivity and submicromolar potency at hAChE. Cell-based assays of BBB permeation, neurotoxicity, and neuroprotection supported the potential of compound 37 as a BBB-permeant neuroprotective agent against H2O2-induced oxidative stress with poor interaction as P-gp substrate and very low cytotoxicity

Bioinformatics and molecular modeling in glycobiology

The field of glycobiology is concerned with the study of the structure, properties, and biological functions of the family of biomolecules called carbohydrates. Bioinformatics for glycobiology is a particularly challenging field, because carbohydrates exhibit a high structural diversity and their chains are often branched. Significant improvements in experimental analytical methods over recent years have led to a tremendous increase in the amount of carbohydrate structure data generated. Consequently, the availability of databases and tools to store, retrieve and analyze these data in an efficient way is of fundamental importance to progress in glycobiology. In this review, the various graphical representations and sequence formats of carbohydrates are introduced, and an overview of newly developed databases, the latest developments in sequence alignment and data mining, and tools to support experimental glycan analysis are presented. Finally, the field of structural glycoinformatics and molecular modeling of carbohydrates, glycoproteins, and protein–carbohydrate interaction are reviewed

Comparison of docking methods for carbohydrate binding in calcium-dependent lectins and prediction of the carbohydrate binding mode to sea cucumber lectin CEL-III

International audienc

How the flexibility of human histone deacetylases influences ligand binding: an overview.

Over the past decade, human histone deacetylases (HDACs) have become interesting as therapeutic targets because of the benefits that their modulation might provide in aging-related disorders. Recently, studies using crystallography and computational chemistry have provided information on the structure and conformational changes related to HDAC-mediated recognition events. Through the description of the key mass and one-off movements observed in metal-dependent HDACs, here we highlight the impact of flexibility on drug-binding affinity and specificity. The collected information will be useful for not only a better understanding of the biological functions of HDACs, but also the conception of new selective binders

Role of water molecules in structure and energetics of <i>Pseudomonas aeruginosa</i> lectin I interacting with disaccharides

International audienc