The novel drug candidate VOMG kills Mycobacterium abscessus and other pathogens by inhibiting cell division.

Aims: The incidence of lung infections is increasing worldwide in individuals suffering from cystic fibrosis and chronic obstructive pulmonary disease. Mycobacterium abscessus is associated with chronic lung deterioration in these populations. The intrinsic resistance of M.

Imidazoquinoline Derivatives as Potential Inhibitors of InhA Enzyme and .

Tuberculosis is a serious public health problem worldwide. The search for new antibiotics has become a priority, especially with the emergence of resistant strains. A new family of imidazoquinoline derivatives, structurally analogous to triazolophthalazines, which had previously shown good antituberculosis activity, were designed to inhibit InhA, an essential enzyme for survival.

Developing a Biomimetic 3D Neointimal Layer as a Prothrombotic Substrate for a Humanized In Vitro Model of Atherothrombosis.

Acute cardiovascular events result from clots caused by the rupture and erosion of atherosclerotic plaques. This paper aimed to produce a functional biomimetic hydrogel of the neointimal layer of the atherosclerotic plaque that can support thrombogenesis upon exposure to human blood. A biomimetic hydrogel of the neointima was produced by culturing THP-1-derived foam cells within 3D collagen hydrogels in the presence or absence of atorvastatin.

Mast Cell Activation Profile and TFH13 Detection Discriminate Food Anaphylaxis Versus Sensitization.

Background And Objective: The prevalence of food allergy (FA) has increased significantly, and the risk of developing anaphylaxis is unpredictable. Thus, discriminating between sensitized patients and those at risk of having a severe reaction is of utmost interest. To explore mast cell activation pattern and T follicular helper (TFH) 13 presence in sensitized and food anaphylaxis patients.

Exploring the plasticity of the InhA substrate-binding site using new diaryl ether inhibitors.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a worldwide scourge with more than 10 million people affected yearly. Among the proteins essential for the survival of Mtb, InhA has been and is still clinically validated as a therapeutic target. A new family of direct diaryl ether inhibitors, not requiring prior activation by the catalase peroxidase enzyme KatG, has been designed with the ambition of fully occupying the InhA substrate-binding site.

Multi-Criterial Model for Weighting Biological Risk Factors in Multiple Sclerosis: Clinical and Health Insurance Implications.

The etiology of Multiple Sclerosis (MS) remains undetermined. Its pathogenic risk factors are thought to play a negligible role individually in the development of the disease, instead assuming a pathogenic role when they interact with each other. Unfortunately, the statistical weighting of this pathogenic role in predicting MS risk is currently elusive, preventing clinical and health insurance applications.

CanB, a Druggable Cellular Target in .

Treatment against tuberculosis can lead to the selection of drug-resistant strains. To tackle this serious threat, new targets from are needed to develop novel effective drugs. In this work, we aimed to provide a possible workflow to validate new targets and inhibitors by combining genetic, , and enzymological approaches.

Teachers during COVID-19: Examining burnout levels and their work-life.

Background: In March 2020, with the scope to reduce the spread of COVID-19, most national governments around the world canceled in-person education and moved to online learning. Therefore, teachers and students had to adapt a new way of teaching. Most of Italian teachers never had such an experience before and encountered difficulties in effectively carrying out this process on their own.

Implementing best practices on data generation and reporting of assays within the ERA4TB consortium.

Tuberculosis (TB) is the historical leading cause of death by a single infectious agent. The European Regimen Accelerator for Tuberculosis (ERA4TB) is a public-private partnership of 30+ institutions with the objective to progress new anti-TB regimens into the clinic. Thus, robust and replicable results across independent laboratories are essential for reliable interpretation of treatment efficacy.

Infections in Cystic Fibrosis Individuals: A Review on Therapeutic Options.

is an opportunistic pathogen that mainly colonizes and infects cystic fibrosis patients' lungs. is naturally resistant to many antibiotics such as rifamycin, tetracyclines and β-lactams. The current therapeutic regimens are not very effective and are mostly based on repurposed drugs used against infections.

New Drugs and Novel Cellular Targets against Tuberculosis.

() is the etiological agent of tuberculosis (TB), one of the most life-threatening communicable diseases, which causes 10 million new cases each year and results in an estimated 1 [...

Expanding the knowledge around antitubercular 5-(2-aminothiazol-4-yl)isoxazole-3-carboxamides: Hit-to-lead optimization and release of a novel antitubercular chemotype via scaffold derivatization.

Tuberculosis is one of the deadliest infectious diseases in the world, and the increased number of multidrug-resistant and extensively drug-resistant strains is a reason for concern. We have previously reported a series of substituted 5-(2-aminothiazol-4-yl)isoxazole-3-carboxamides with growth inhibitory activity against Mycobacterium tuberculosis strains and low propensity to be substrate of efflux pumps. Encouraged by these preliminary results, we have undertaken a medicinal chemistry campaign to determine the metabolic fate of these compounds and to delineate a reliable body of Structure-Activity Relationships.

A New Benzothiazolthiazolidine Derivative, 11726172, Is Active , , and against Nonreplicating Cells of Mycobacterium tuberculosis.

Tuberculosis (TB) still poses a global menace as one of the deadliest infectious diseases. A quarter of the human population is indeed latently infected with Mycobacterium tuberculosis. People with latent infection have a 5 to 10% lifetime risk of becoming ill with TB, representing a reservoir for TB active infection.

Intermediate-Intensity Autologous Hematopoietic Stem Cell Transplantation Reduces Serum Neurofilament Light Chains and Brain Atrophy in Aggressive Multiple Sclerosis.

Background: Autologous haematopoietic stem cell transplantation (AHSCT) is highly effective in reducing new inflammatory activity in aggressive multiple sclerosis (MS). A remarkable decrease of serum neurofilament light chains (sNfL) concentration, a marker of axonal damage, was reported in MS following high-intensity regimen AHSCT, but hints for potential neurotoxicity had emerged. sNfL and brain atrophy were therefore analysed in a cohort of patients with aggressive MS treated with intermediate-intensity AHSCT, exploring whether sNfL might be a reliable marker of disability progression independent from new inflammation (i.

The Veterinary Anti-Parasitic Selamectin Is a Novel Inhibitor of the DprE1 Enzyme.

Avermectins are macrocyclic lactones with anthelmintic activity. Recently, they were found to be effective against , which accounts for one third of the worldwide deaths from antimicrobial resistance. However, their anti-mycobacterial mode of action remains to be elucidated.

The Antimalarial Mefloquine Shows Activity against , Inhibiting Mycolic Acid Metabolism.

Some nontuberculous mycobacteria (NTM) are considered opportunistic pathogens. Nevertheless, NTM infections are increasing worldwide, becoming a major public health threat. Furthermore, there is no current specific drugs to treat these infections, and the recommended regimens generally lack efficacy, emphasizing the need for novel antibacterial compounds.

A Coumarin-Based Analogue of Thiacetazone as Dual Covalent Inhibitor and Potential Fluorescent Label of HadA in .

A novel coumarin-based molecule, designed as a fluorescent surrogate of a thiacetazone-derived antitubercular agent, was quickly and easily synthesized from readily available starting materials. This small molecule, coined , exhibited a combination of appropriate physicochemical and biological properties, including resistance toward hydrolysis and excellent antitubercular efficiency similar to that of well-known thiacetazone derivatives, as well as efficient covalent labeling of HadA, a relevant therapeutic target to combat . More remarkably, was successfully implemented as an imaging probe that is capable of labeling in a selective manner, with an enrichment at the level of the poles, thus giving relevant insights about the polar localization of HadA in the mycobacteria.

Promoting the propensity for blood donation through the understanding of its determinants.

Background: The paper aims to understand the main antecedents related to the blood donation propensity related to both donors and non-donors. With our research, we will analyse the two perspectives to identify similarities and differences concentrating on the Italian context. Blood is a vital resource that strongly affects every national healthcare system's efficacy and sustainability and the system's ability to achieve the goal of universal coverage.

Gut Microbial Signatures in Sporadic and Hereditary Colorectal Cancer.

Colorectal cancer (CRC) is the fourth most common cause of cancer-related death and the third most common cancer in the world. Depending on the origin of the mutation, colorectal carcinomas are classified as sporadic or hereditary. Cancers derived from mutations appearing during life, affecting individual cells and their descendants, are called sporadic and account for almost 95% of the CRCs.

Design and Synthesis of Pyrano[3,2-]indolones Showing Antimycobacterial Activity.

Latent infection presents one of the largest challenges for tuberculosis control and novel antimycobacterial drug development. A series of pyrano[3,2-]indolone-based compounds was designed and synthesized via an original eight-step scheme. The synthesized compounds were evaluated for their activity against strains H37Rv and streptomycin-starved 18b (SS18b), representing models for replicating and nonreplicating mycobacteria, respectively.

Nitric oxide-releasing compounds for the treatment of lung infections.

The spread of acquired drug resistance and of microorganisms naturally resistant to antibiotics is a major threat to global health, leading to an urgent need for novel antimicrobial compounds. Exogenous nitric oxide (NO) represents an attractive and promising antimicrobial approach, showing both bactericidal and biofilm dispersal activities. Numerous studies have been performed to develop NO donor scaffolds, including small molecules, macromolecular compounds, nanoparticles (NPs), and polymeric materials.

Sustained disease remission after discontinuation of disease modifying treatments in relapsing-remitting multiple sclerosis.

Background: The natural history of multiple sclerosis (MS) following discontinuation of a first-line disease-modifying treatment (DMT) in relapsing-remitting (RR-) MS patients is controversial, as few data are available on the risk of disease reactivation. This study aims to investigate the disease course after DMT discontinuation in selected RR-MS patients, exploring potential predictive factors of disease reactivation.

Methods: RR-MS patients, aged 18-65, who had discontinued a first-line DMT were selected from 1107 clinical records.

Study of Bedaquiline Resistance in Multi-Drug Resistant Clinical Isolates.

Tuberculosis (TB) is one of the major causes of death related to antimicrobial resistance worldwide because of the spread of multi- and extensively drug resistant (multi-drug resistant (MDR) and extensively drug-resistant (XDR), respectively) clinical isolates. To fight MDR and XDR tuberculosis, three new antitubercular drugs, bedaquiline (BDQ), delamanid, and pretomanid were approved for use in clinical setting. Unfortunately, BDQ quickly acquired two main mechanisms of resistance, consisting in mutations in either gene, encoding the target, or in , coding for the repressor of the MmpS5-MmpL5 efflux pump.

2-Aminooxazole as a Novel Privileged Scaffold in Antitubercular Medicinal Chemistry.

To obtain effective eradication of numerous infectious diseases such as tuberculosis, it is important to supply the medicinal chemistry arsenal with novel chemical agents. Isosterism and bioisosterism are widely known concepts in the field of early drug discovery, and in several cases, rational isosteric replacements have contributed to improved efficacy and physicochemical characteristics throughout the hit-to-lead optimization process. However, sometimes the synthesis of isosteres might not be as straightforward as that of the parent compounds, and therefore, novel synthetic strategies must be elaborated.