Recent Advances in the Discovery of Novel Drugs on Natural Molecules.

Natural products (NPs) are always a promising source of novel drugs for tackling unsolved diseases [...

Postharvest Quality of L. (cv Liscia-Diamante) Fruit Stored at Different Temperatures: Volatile Profile and Antimicrobial Activity of Essential Oils.

Citron ( L. cv. Liscia-diamante), cultivated in the "Riviera dei Cedri" (southern Italy), is mainly utilized in the production of candied fruit and essential oils (EOs).

Allergic Conjunctivitis Management: Update on Ophthalmic Solutions.

Purpose Of Review: The aim of this review, is to present an updated revision of topical management of SAC and PAC, based on the available scientific evidence and focused on the impact of ophthalmic solution formulations on eye surface.

Recent Findings: Physicians treating ocular allergy should be aware of tear film and tear film disruption in SAC and PAC, and how eye drop composition and additives affect the physiology of the allergic eye. Seasonal and perennial allergic conjunctivitis (SAC and PAC) are the most frequent causes of ocular allergy (OA), and both conditions are underdiagnosed and undertreated.

A genetic algorithm-based approach for the prediction of metabolic drug-drug interactions involving CYP2C8 or CYP2B6.

Background And Objectives: A genetic algorithm (GA) approach was developed to predict drug-drug interactions (DDIs) caused by cytochrome P450 2C8 (CYP2C8) inhibition or cytochrome P450 2B6 (CYP2B6) inhibition or induction. Nighty-eight DDIs, obtained from published in vivo studies in healthy volunteers, have been considered using the area under the plasma drug concentration-time curve (AUC) ratios (i.e.

Milk and Its Derivatives as Sources of Components and Microorganisms with Health-Promoting Properties: Probiotics and Bioactive Peptides.

Milk is a source of many valuable nutrients, including minerals, vitamins and proteins, with an important role in adult health. Milk and dairy products naturally containing or with added probiotics have healthy functional food properties. Indeed, probiotic microorganisms, which beneficially affect the host by improving the intestinal microbial balance, are recognized to affect the immune response and other important biological functions.

Prolonging the stability of cetuximab (Erbitux®) and panitumumab (Vectibix®): An orthogonal assessment of physicochemical, biological and microbiological properties of original opened glass vials and diluted saline preparations.

The two anti-epidermal growth factor receptor monoclonal antibodies (mAbs) cetuximab and panitumumab are the pillars for the treatment of EGFR-positive, KRAS wild-type metastatic colorectal cancers. However, stability data of these mAbs are generally missing or incomplete. Here, we report for the first time an orthogonal analysis of the stability of cetuximab (Erbitux®) and panitumumab (Vectibix®), either undiluted vial leftovers or saline dilutions in polyolefin/polyamide infusion bags.

Alternative Protein Sources and Novel Foods: Benefits, Food Applications and Safety Issues.

The increasing size of the human population and the shortage of highly valuable proteinaceous ingredients has prompted the international community to scout for new, sustainable, and natural protein resources from invertebrates (e.g., insects) and underutilized legume crops, unexploited terrestrial and aquatic weeds, and fungi.

Effect of Gaseous Citral on Table Grapes Contaminated by ITEM 18876.

is responsible for rapidly producing a deliquescent appearance in grape berries, generally favoured by cold chain interruptions. To counteract fruit spoilage and to meet consumer acceptance, innovative strategies based on the application of natural compounds are ongoing. Due to their biological activities, including antimicrobial ones, natural flavour compounds extend the shelf life and improve the nutritional value as well as the organoleptic properties of foods.

Quantitative Prediction of Drug Interactions Caused by Cytochrome P450 2B6 Inhibition or Induction.

Background: Numerous drugs have the potential to be affected by cytochrome P450 (CYP) 2B6-mediated drug-drug interactions (DDIs).

Objectives: In this work, we extend a static approach to the prediction of the extent of pharmacokinetics DDIs between substrates and inhibitors or inducers of CYP2B6.

Methods: This approach is based on the calculation of two parameters (the contribution ratio [CR], representing the fraction of dose of the substrate metabolized via this pathway and the inhibitory or inducing potency of the perpetrator [IR or IC, respectively]) calculated from the area under the concentration-time curve (AUC) ratios obtained in in-vivo DDI studies.

Rational Discovery of Antiviral Whey Protein-Derived Small Peptides Targeting the SARS-CoV-2 Main Protease.

In the present work, and for the first time, three whey protein-derived peptides (IAEK, IPAVF, MHI), endowed with ACE inhibitory activity, were examined for their antiviral activity against the SARS-CoV-2 3C-like protease (3CL) and Human Rhinovirus 3C protease (3C) by employing molecular docking. Computational studies showed reliable binding poses within 3CL for the three investigated small peptides, considering docking scores as well as the binding free energy values. Validation by in vitro experiments confirmed these results.

The Nitrobenzoxadiazole Derivative NBDHEX Behaves as Gametocyte Selective Inhibitor with Malaria Parasite Transmission Blocking Activity.

This work describes the activity of 6-((7-nitrobenzo[][1,2,5]oxadiazol-4-yl)thio)hexan-1-ol (NBDHEX) and of its newly identified carboxylic acid metabolite on the human malaria parasite . NBDHEX has been previously identified as a potent cytotoxic agent against murine and human cancer cells as well as towards the protozoan parasite . We show here that NBDHEX is active in vitro against all blood stages of , with the rare feature of killing the parasite stages transmissible to mosquitoes, the gametocytes, with a 4-fold higher potency than that on the pathogenic asexual stages.

Determinants of Drug Resistance in B-Cell Non-Hodgkin Lymphomas: The Case of Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia.

Lymphoplasmacytic lymphoma (LPL) is a rare subtype of B cell-derived non-Hodgkin lymphoma characterized by the abnormal growth of transformed clonal lymphoplasmacytes and plasma cells. This tumor almost always displays the capability of secreting large amounts of monoclonal immunoglobulins (Ig) of the M class (Waldenström Macroglobulinemia, WM). The clinical manifestations of WM/LPL may range from an asymptomatic condition to a lymphoma-type disease or may be dominated by IgM paraprotein-related symptoms.

Recent Advances in the Mechanisms and Regulation of QS in Dairy Spoilage by spp.

Food spoilage is a serious issue dramatically impacting the worldwide need to counteract food insecurity. Despite the very expensive application of low temperatures, the proper conservation of fresh dairy products is continuously threatened at different stages of production and commercialization by psychrotrophic populations mainly belonging to the genus. These bacteria cause discolouration, loss of structure, and off-flavours, with fatal implications on the quality and shelf-life of products.

A Quantitative Approach to the Prediction of Drug-Drug Interactions Mediated by Cytochrome P450 2C8 Inhibition.

Background: Ohno and Colleagues proposed an approach for predicting drug-drug interactions (DDIs) mediated by cytochrome P450 (CYP) 3A4 based on the use of the ratio of the inhibited to non-inhibited area under the plasma concentration time curve (AUC) of substrates to estimate the fraction of the dose metabolized via CYP3A4 (contribution ratio, CR) and the inhibitory potency of a perpetrator (inhibition ratio, IR). This study evaluated the performance of this approach on DDIs mediated by CYP2C8 inhibitors.

Research Design And Methods: Initial estimates of CR and IR of CYP2C8 substrates and inhibitors were calculated for 33 DDI studies.

Insights into the cellular pharmacokinetics and pharmacodynamics of thiopurine antimetabolites in a model of human intestinal cells.

Thiopurines, immunomodulating drugs used in the management of different chronic autoimmune conditions and as anti-leukemic agents, may exert in some cases gastrointestinal toxicity. Moreover, since these agents are administered orally, they are absorbed across the gastrointestinal tract epithelium. On these premises, cellular and molecular events occurring in intestinal cells may be important to understand thiopurine effects.

Cell-Secreted Vesicles: Novel Opportunities in Cancer Diagnosis, Monitoring and Treatment.

Extracellular vesicles (EVs) are important mediators of intercellular communication playing a pivotal role in the regulation of physiological and pathological processes, including cancer. In particular, there is significant evidence suggesting that tumor-derived EVs exert an immunosuppressive activity during cancer progression, as well as stimulate tumor cell migration, angiogenesis, invasion and metastasis. The use of EVs as a liquid biopsy is currently a fast-growing area of research in medicine, with the potential to provide a step-change in the diagnosis and treatment of cancer, allowing the prediction of both therapy response and prognosis.

Densely Functionalized 2-Methylideneazetidines: Evaluation as Antibacterials.

Twenty-two novel, variously substituted nitroazetidines were designed as both sulfonamide and urethane vinylogs possibly endowed with antimicrobial activity. The compounds under study were obtained following a general procedure recently developed, starting from 4-nitropentadienoates deriving from a common β-nitrothiophenic precursor. While being devoid of any activity against fungi and Gram-negative bacteria, most of the title compounds performed as potent antibacterial agents on Gram-positive bacteria ( and three strains of ), with the most potent congener being the 1-(4-chlorobenzyl)-3-nitro-4-(-tolyl)azetidine , which displayed potency close to that of norfloxacin, the reference antibiotic (minimum inhibitory concentration values 4 and 1-2 μg/mL, respectively).

Molecular Simplification of Natural Products: Synthesis, Antibacterial Activity, and Molecular Docking Studies of Berberine Open Models.

Berberine, the main bioactive component of many medicinal plants belonging to various genera such as , , and is a multifunctional compound. Among the numerous interesting biological properties of berberine is broad antimicrobial activity including a range of Gram-positive and Gram-negative bacteria. With the aim of identifying berberine analogues possibly endowed with higher lead-likeness and easier synthetic access, the molecular simplification approach was applied to the secondary metabolite and a series of analogues were prepared and screened for their antimicrobial activity against Gram-positive and Gram-negative bacterial test species.

Mycotoxin Removal by spp. and Their Application in Animal Liquid Feed.

The removal of mycotoxins from contaminated feed using lactic acid bacteria (LAB) has been proposed as an inexpensive, safe, and promising mycotoxin decontamination strategy. In this study, viable and heat-inactivated CIP 76.13T and subsp.

Phenotypic and genomic characterization of ITEM 17297 spoiler of fresh vegetables: Focus on biofilm and antibiotic resistance interaction.

is widely recognized as a spoiler of fresh foods under cold storage, and recently associated also with infections in clinical settings. The presence of antibiotic resistance genes (ARGs) could be acquired and transmitted by horizontal genetic transfer and further increase the risk associated with its persistence in food and the need to be deeper investigated. Thus, in this work we presented a genomic and phenotypic analysis of the psychrotrophic ITEM 17297 to provide new insight into AR mechanisms by this species until now widely studied only for its spoilage traits.

Combined Effect of Active Packaging of Polyethylene Filled with a Nano-Carrier of Salicylate and Modified Atmosphere to Improve the Shelf Life of Fresh Blueberries.

Blueberries are popular among consumers for their high nutritional value but are highly perishable due to the microbial decay. The use of active packaging that is able to interact with the food through releasing or absorbing substances can be a valid approach to preserve the quality and increase the fruit's shelf-life. In this paper, an active packaging based on polyethylene (PE) filled with a nano-carrier of salicylate was prepared and characterized.