Angioleiomyoma of the Sinonasal Tract: A Systematic Review of an Uncommon Clinicopathological Entity.

 Angioleiomyoma is a rare neoplasm that represents ∼ 0.2 % of all head and neck benign tumors and ∼ 2% of total cases of tumors of the sinonasal tract. It was once considered a possible subtype of leiomyoma, but, in the 2020 World Health Organization (WHO) classification of soft tissue tumors, it is accepted as a singular entity.

Dynamic-shared Pharmacophore Approach as Tool to Design New Allosteric PRC2 Inhibitors, Targeting EED Binding Pocket.

The Polycomb Repressive complex 2 (PRC2) maintains a repressive chromatin state and silences many genes, acting as methylase on histone tails. This enzyme was found overexpressed in many types of cancer. In this work, we have set up a Computer-Aided Drug Design approach based on the allosteric modulation of PRC2.

Targeting SARS-CoV-2 RBD Interface: a Supervised Computational Data-Driven Approach to Identify Potential Modulators.

Coronavirus disease 2019 (COVID-19) has spread out as a pandemic threat affecting over 2 million people. The infectious process initiates via binding of SARS-CoV-2 Spike (S) glycoprotein to host angiotensin-converting enzyme 2 (ACE2). The interaction is mediated by the receptor-binding domain (RBD) of S glycoprotein, promoting host receptor recognition and binding to ACE2 peptidase domain (PD), thus representing a promising target for therapeutic intervention.

A New Family of Jumonji C Domain-Containing KDM Inhibitors Inspired by Natural Product Purpurogallin.

Aberrant epigenetic modifications are involved in cancer development. Jumonji C domain-containing histone lysine demethylases (KDMs) are found mainly up-regulated in breast, prostate, and colon cancer. Currently, growing interest is focusing on the identification and development of new inhibitors able to block the activity of KDMs and thus reduce tumor progression.

3-(6-Phenylimidazo [2,1-][1,3,4]thiadiazol-2-yl)-1-Indole Derivatives as New Anticancer Agents in the Treatment of Pancreatic Ductal Adenocarcinoma.

A new series of imidazo[2,1-][1,3,4]thiadiazole derivatives was efficiently synthesized and screened for their antiproliferative activity on a panel of pancreatic ductal adenocarcinoma (PDAC) cells, including SUIT-2, Capan-1 and Panc-1. Compounds and , showed relevant antiproliferative activity on all three pre-clinical models with half maximal inhibitory concentration (IC) ranging from 5.11 to 10.

In Silico Insights towards the Identification of NLRP3 Druggable Hot Spots.

NLRP3 (NOD-like receptor family, pyrin domain-containing protein 3) activation has been linked to several chronic pathologies, including atherosclerosis, type-II diabetes, fibrosis, rheumatoid arthritis, and Alzheimer's disease. Therefore, NLRP3 represents an appealing target for the development of innovative therapeutic approaches. A few companies are currently working on the discovery of selective modulators of NLRP3 inflammasome.

An overview of recent molecular dynamics applications as medicinal chemistry tools for the undruggable site challenge.

Molecular dynamics (MD) has become increasingly popular due to the development of hardware and software solutions and the improvement in algorithms, which allowed researchers to scale up calculations in order to speed them up. MD simulations are usually used to address protein folding issues or protein-ligand complex stability through energy profile analysis over time. In recent years, the development of new tools able to deeply explore a potential energy surface (PES) has allowed researchers to focus on the dynamic nature of the binding recognition process and binding-induced protein conformational changes.

The Use of Dynamic Pharmacophore in Computer-Aided Hit Discovery: A Case Study.

In recent years pharmacophore modeling has become increasingly popular due to the development of software solutions and improvement in algorithms that allowed researchers to focus on interactions between protein and ligands instead of technical details of the software. At the same time, progress in computer hardware made molecular dynamics (MD) simulations on regular PC hardware possible. MD simulations are usually used, within the virtual screening process, to take into account the flexibility of the target and studying it in more realistic way.

A Molecular Dynamics-Shared Pharmacophore Approach to Boost Early-Enrichment Virtual Screening: A Case Study on Peroxisome Proliferator-Activated Receptor α.

Molecular dynamics (MD) simulations can be used, prior to virtual screening, to add flexibility to proteins and study them in a dynamic way. Furthermore, the use of multiple crystal structures of the same protein containing different co-crystallized ligands can help elucidate the role of the ligand on a protein's active conformation, and then explore the most common interactions between small molecules and the receptor. In this work, we evaluated the contribution of the combined use of MD on crystal structures containing the same protein but different ligands to examine the crucial ligand-protein interactions within the complexes.

Polyglutamine- and temperature-dependent conformational rigidity in mutant huntingtin revealed by immunoassays and circular dichroism spectroscopy.

Background: In Huntington's disease, expansion of a CAG triplet repeat occurs in exon 1 of the huntingtin gene (HTT), resulting in a protein bearing>35 polyglutamine residues whose N-terminal fragments display a high propensity to misfold and aggregate. Recent data demonstrate that polyglutamine expansion results in conformational changes in the huntingtin protein (HTT), which likely influence its biological and biophysical properties. Developing assays to characterize and measure these conformational changes in isolated proteins and biological samples would advance the testing of novel therapeutic approaches aimed at correcting mutant HTT misfolding.

Searching for Dual Inhibitors of the MDM2-p53 and MDMX-p53 Protein-Protein Interaction by a Scaffold-Hopping Approach.

Two libraries of substituted benzimidazoles were designed using a 'scaffold-hopping' approach based on reported MDM2-p53 inhibitors. Substituents were chosen following library enumeration and docking into an MDM2 X-ray structure. Benzimidazole libraries were prepared using an efficient solution-phase approach and screened for inhibition of the MDM2-p53 and MDMX-p53 protein-protein interactions.

P6 acupressure effectiveness on acute vertiginous patients: a double blind randomized study.

Objectives: The purpose of this study was to evaluate the effectiveness of P6 acupressure on vertigo and neurovegetative symptoms, its possible interference with vestibular-ocular reflex (VOR), and its clinical usefulness during acute vertigo.

Materials And Methods: Two hundred and four patients, either affected by acute vertigo (n=124) or undergoing labyrinth stimulation (n=80), were randomly divided in two homogeneous groups: an experimental group A and a placebo group B. Each patient rated severity of vertigo and neurovegetative symptoms on a visuo-analogue scale ranging from 0 to 10, before and after bilateral placement of a P6 device.

In silico scaffold evaluation and solid phase approach to identify new gelatinase inhibitors.

Among matrix metalloproteinases (MMPs), gelatinases MMP-2 (gelatinase A) and MMP-9 (gelatinase B) play a key role in a number of physiological processes such as tissue repair and fibrosis. Many evidences point out their involvement in a series of pathological events, such as arthritis, multiple sclerosis, cardiovascular diseases, inflammatory processes and tumor progression by degradation of the extracellular matrix. To date, the identification of non-specific MMP inhibitors has made difficult the selective targeting of gelatinases.

Molecular interaction fields and 3D-QSAR studies of p53-MDM2 inhibitors suggest additional features of ligand-target interaction.

The design and optimization of small molecule inhibitors of the murine double minute clone 2-p53 (p53-MDM2) interaction has attracted a great deal of interest as a way to novel anticancer therapies. Herein we report 3D-QSAR studies of 41 small molecule inhibitors based on the use of molecular interaction fields and docking experiments as part of an approach to generating predictive models of MDM2 affinity and shedding further light on the structural elements of the ligand-target interaction. These studies have yielded predictive models explaining much of the variance of the 41 compound training set and satisfactorily predicting with 75% success an external test set of 36 compounds.

Fragmenting the S100B-p53 interaction: combined virtual/biophysical screening approaches to identify ligands.

S100B contributes to cell proliferation by binding the C terminus of p53 and inhibiting its tumor suppressor function. The use of multiple computational approaches to screen fragment libraries targeting the human S100B-p53 interaction site is reported. This in silico screening led to the identification of 280 novel prospective ligands.

Dual-energy X-ray absorptiometry analysis of body composition in patients affected by OSAS.

Obstructive sleep apnoea syndrome (OSAS) is a disorder characterized by recurrent episodes of apnoea. This study evaluates the body composition in OSAS patients compared to normal weight, pre-obese and obese subjects. Body composition has been measured by dual-energy X-ray absorptiometry in the whole body and in three different body regions.

Straightforward recursive partitioning model for discarding insoluble compounds in the drug discovery process.

Poor aqueous solubility is one of the major issues in drug discovery and development, impacting negatively on all aspects of the research and development process. The pharmaceutical industry has realized that solubility issues need to be resolved at the discovery stage. We here present an innovative way to address this problem via a model designed to address the simple question, "Is the compound likely to be sufficiently soluble to provide interpretable data in biological screening assays?" A recursive partitioning (RP) method was applied to a set of 3563 molecules, with in house determined aqueous solubility values.

Parallel synthesis of a series of potentially brain penetrant aminoalkyl benzoimidazoles.

Alpha7 agonists were identified via GOLD (CCDC) docking in the putative agonist binding site of an alpha7 homology model and a series of aminoalkyl benzoimidazoles was synthesised to obtain potentially brain penetrant drugs. The array was prepared starting from the reaction of ortho-fluoronitrobenzenes with a selection of diamines, followed by reduction of the nitro group to obtain a series of monoalkylated phenylene diamines. N,N'-Carbonyldiimidazole (CDI) mediated acylation, followed by a parallel automated work-up procedure, afforded the monoacylated phenylenediamines which were cyclised under acidic conditions.

Voice disorders and posturography: variables to define the success of rehabilitative treatment.

Previous studies have investigated the relationship between muscular tension, body posture, and voice quality. The aim of this paper is to study the postural pattern during voice production in healthy subjects compared with patients affected by voice disorders and in the same patients before and after vocal treatment by means of static posturography. Classic posturographic variables and spectral frequency analysis of body sway have been measured.

Paroxysmal positional vertigo in skeet shooters and hunters.

Paroxysmal positional vertigo (PPV) is a high prevalence vestibular end organ disorder due to the detachment of the utricular otoconia floating in the posterior or lateral semicircular canal. In the majority of cases the etiology of PPV is unknown and it may follow viral infections, vascular disorders and head trauma. This report presents six cases (out of 520 diagnoses of PPV) of PPV following repeated training sessions of skeet shooting or gun shooting during animal hunting.

Epithelioid haemangioendothelioma arising in the nasal cavity.

We report here the case of an epithelioid haemangioendothelioma (EHE) arising in the nasal cavity which is, to the best of our knowledge, the first ever described example in the world literature in that particular site. The patient is a 23-year-old male who presented with repeated episodes of epistaxis from the nasal cavity and with a 1.5 cm reddish, polypoid, smooth, spontaneously bleeding nodule in the right middle meatus.