Eotaxin-3 is a key chemokine with a relevant role in eosinophilic esophagitis, a rare chronic immune/antigen-mediated inflammatory disorder. Eotaxin-3 is a potent activator of eosinophil emergence and migration, which may lead to allergic airway inflammation. We investigated, using bioinformatics tools, the protein structure and the possible effects of the known variations reported in public databases.
View Article and Find Full Text PDFThe purple carrot cultivar 'Purple Sun' ( L.) is characterized by a relevant content of phenolic compounds and anthocyanins, which may play an important role in reducing the risk of chronic diseases and in the treatment of metabolic syndrome. In the present study, the genetic diversity, phytochemical composition, and bioactivities of this outstanding variety were studied for the first time.
View Article and Find Full Text PDFLipoxygenases make several biological functions in cells, based on the products of the catalyzed reactions. In diatoms, microalgae ubiquitous in aquatic ecosystems, lipoxygenases have been noted for the oxygenation of fatty acids with the production of oxylipins, which are involved in many physiological and pathological processes in marine organisms. The interest in diatoms' lipoxygenases and oxylipins has increased due to their possible biotechnological applications, ranging from ecology to medicine.
View Article and Find Full Text PDFThe affinity of specific phenolic compounds (PCs) and capsaicinoids (CAPs) present in three varieties (Friariello, Cayenne and Dzuljunska Sipka) to the transient receptor potential vanilloid member 1 (TRPV1) was investigated by integrating an analytic approach for the simultaneous extraction and analysis through high-performance liquid chromatography coupled with ion trap mass spectrometry (HPLC/ITMS) and UV detection (HPLC-UV) of PCs and CAPs and structural bioinformatics based on the protein modelling and molecular simulations of protein-ligand docking. Overall, a total of 35 compounds were identified in the different samples and CAPs were quantified. The highest content of total polyphenols was recorded in the pungent Dzuljunska Sipka variety (8.
View Article and Find Full Text PDFEpigenetic mechanisms finely regulate gene expression and represent potential therapeutic targets. Cambinol is a synthetic heterocyclic compound that inhibits class III histone deacetylases known as sirtuins (SIRTs). The acetylating action that results could be crucial in modulating cellular functions via epigenetic regulations.
View Article and Find Full Text PDFThe aryl hydrocarbon receptor (AhR) is a highly conserved environmental sensor, historically known for mediating the toxicity of xenobiotics. It is involved in numerous cellular processes such as differentiation, proliferation, immunity, inflammation, homeostasis, and metabolism. It exerts a central role in several conditions such as cancer, inflammation, and aging, acting as a transcription factor belonging to the basic helix-loop-helix/Per-ARNT-Sim (bHLH-PAS) protein family.
View Article and Find Full Text PDFCollectively, rare genetic disorders affect a substantial portion of the world's population. In most cases, those affected face difficulties in receiving a clinical diagnosis and genetic characterization. The understanding of the molecular mechanisms of these diseases and the development of therapeutic treatments for patients are also challenging.
View Article and Find Full Text PDFDiabetes is a chronic, metabolic disease characterized by high blood sugar levels. Among the main types of diabetes, type 2 is the most common. Early diagnosis and treatment can prevent or delay the onset of complications.
View Article and Find Full Text PDFInvestigating large datasets of biological information by automatic procedures may offer chances of progress in knowledge. Recently, tremendous improvements in structural biology have allowed the number of structures in the Protein Data Bank (PDB) archive to increase rapidly, in particular those for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated proteins. However, their automatic analysis can be hampered by the nonuniform descriptors used by authors in some records of the PDB and PDBx/mmCIF files.
View Article and Find Full Text PDFNatural products and plant extracts exhibit many biological activities, including that related to the defense mechanisms against parasites. Many studies have investigated the biological functions of secondary metabolites and reported evidence of antiviral activities. The pandemic emergencies have further increased the interest in finding antiviral agents, and efforts are oriented to investigate possible activities of secondary plant metabolites against human viruses and their potential application in treating or preventing SARS-CoV-2 infection.
View Article and Find Full Text PDFBackground: Despite recent improvements in therapy, the five-year survival rate for patients with advanced melanoma is poor, mainly due to the development of drug resistance. The aim of the present study was to investigate the mechanisms underlying this phenomenon, applying proteomics and structural approaches to models of melanoma cells.
Methods: Sublines from two human (A375 and SK-MEL-28) cells with acquired vemurafenib resistance were established, and their proteomic profiles when exposed to denaturation were identified through LC-MS/MS analysis.
The SARS-CoV-2 variant Omicron is characterized, among others, by more than 30 amino acid changes occurring on the spike glycoprotein with respect to the original SARS-CoV-2 spike protein. We report a comprehensive analysis of the effects of the Omicron spike amino acid changes in the interaction with human antibodies, obtained by modeling them into selected publicly available resolved 3D structures of spike-antibody complexes and investigating the effects of these mutations at structural level. We predict that the interactions of Omicron spike with human antibodies can be either negatively or positively affected by amino acid changes, with a predicted total loss of interactions only in a few complexes.
View Article and Find Full Text PDFThe microbial transglutaminase (TGase) from (MTGase) is widely used for industrial applications. However, in the last decades, TGases from other bacteria have been described. We focused our attention on TGase, from (KalbTGase), recently characterized as more selective than MTGase and proposed for applications in drug delivery.
View Article and Find Full Text PDFComputer-aided drug discovery techniques reduce the time and the costs needed to develop novel drugs. Their relevance becomes more and more evident with the needs due to health emergencies as well as to the diffusion of personalized medicine. Pharmacophore approaches represent one of the most interesting tools developed, by defining the molecular functional features needed for the binding of a molecule to a given receptor, and then directing the virtual screening of large collections of compounds for the selection of optimal candidates.
View Article and Find Full Text PDFHuman menin is a nuclear protein that participates in many cellular processes, as transcriptional regulation, DNA damage repair, cell signaling, cell division, proliferation, and migration, by interacting with many other proteins. Mutations of the gene encoding menin cause multiple endocrine neoplasia type 1 (MEN1), a rare autosomal dominant disorder associated with tumors of the endocrine glands. In order to characterize the structural and functional effects at protein level of the hundreds of missense variations, we investigated by computational methods the wild-type menin and more than 200 variants, predicting the amino acid variations that change secondary structure, solvent accessibility, salt-bridge and H-bond interactions, protein thermostability, and altering the capability to bind known protein interactors.
View Article and Find Full Text PDFAn outbreak by a new severe acute respiratory syndrome betacoronavirus (SARS-CoV-2) has spread CoronaVirus Disease 2019 (COVID-19) all over the world. Immediately, following studies have confirmed the human Angiotensin-Converting Enzyme 2 (ACE2) as a cellular receptor of viral Spike-Protein (Sp) that mediates the CoV-2 invasion into the pulmonary host cells. Here, we compared the molecular interactions of the viral Sp from previous SARS-CoV-1 of 2002 and SARS-CoV-2 with the host ACE2 protein by in silico analysis of the available experimental structures of Sp-ACE2 complexes.
View Article and Find Full Text PDFEnzymatic transamidation of gliadins by microbial transglutaminase (mTG) inhibits interferon-γ (IFN-γ) secretion by intestinal T cell lines in patients with celiac disease (CD). To gain insight into the cellular mechanisms underlying the down-regulatory effects of transamidation, we tested a single recombinant α-gliadin (r-gliadin) harbouring two immunodominant peptides, p13 (aa. 120-139) and p23 (aa.
View Article and Find Full Text PDFVolatile organic compounds (VOCs) from 'emitting' plants inform the 'receiving' (listening) plants of impending stresses or simply of their presence. However, the receptors that allow receivers to detect the volatile cue are elusive. Most likely, plants (as animals) have odorant-binding proteins (OBPs), and in fact, a few OBPs are known to bind 'stress-induced' plant VOCs.
View Article and Find Full Text PDFAntimicrobial resistance is spreading massively in the world and is becoming one of the main health threats of the 21st century. One of the possible strategies to overcome this problem is to modify the known classes of antibiotics in a rational way, with the aim of tuning their efficacy. In this paper, we present the synthesis and the evaluation of the biological activity of a series of two β-lactam bearing cephalosporin derivatives, in which an additional isolated azetidinone ring, bearing different substituents, is joined to the classical cephalosporanic nucleus by a chain of variable length.
View Article and Find Full Text PDFDespite the growing interest for microbial transglutaminases (TGases), and the large number of genome sequencing data, there is no deep investigation about structural properties within this family of enzymes in bacteria. We performed a classification of microbial TGases, starting from large-scale analysis of all protein sequences annotated as TGase (more than 8000) in database PFAM. We developed a reiterative procedure based on the construction of several phylogenetic trees and manual selection, and detected five main groups of microbial TGases.
View Article and Find Full Text PDFWe present the synthesis and biological evaluation of the prototype of a new class of cephalosporins, containing an additional isolated beta lactam ring with two phenyl substituents. This new compound is effective against Gram positive microorganisms, with a potency similar to that of ceftriaxone, a cephalosporin widely used in clinics and taken as a reference, and with no cytotoxicity against two different human cell lines, even at a concentration much higher than the minimal inhibitory concentration tested. Additionally, a deep computational analysis has been conducted with the aim of understanding the contribution of its moieties to the binding energy towards several penicillin-binding proteins from both Gram positive and Gram negative bacteria.
View Article and Find Full Text PDFPurpose: To assess magnetic resonance (MR) imaging in depicting the depth of myometrial infiltration, cervical invasion, and presence of enlarged lymph nodes in patients with endometrial adenocarcinoma compared with surgicopathologic findings.
Materials And Methods: Thirty-seven consecutive patients with endometrial carcinoma were included in this prospective study. All patients underwent MR imaging and surgery.