1,721,020 research outputs found
Quercetin-3-oleate
Full text linkPolyphenols are well-known health promoting agents, but they have some limitations due to their spontaneous oxidation. This evidence has limited their use as drugs in recent years. In this field, several chemical modifications have been proposed to overcome these restrictions; among these, esterification seems to be the preferred modification. Ester derivatives may be able to reduce the bioavailability problems connected to polyphenols. On the other hand, the presence of esterase enzymes in the body guarantees ester hydrolysis, which in turn frees the two molecules that make it up. Lipase-catalyzed esterifications gave birth to several derivatives of flavonoids glycosides, in green conditions. In this short paper, pancreatic porcine lipase was firstly used as a cheap bio-catalyst, to synthesize oleoyl derivatives of quercetin in aglycone form. The results demonstrated how the enzyme is able to promote a regioselective acylation on C-3 position, with high yields and easy purification processes
TRPV1-FAAH-COX: The Couples Game in Pain Treatment
Full text linkPain is a complex sensation involving the perception and transduction of diverse environmental pain stimuli with cognitive and emotional processing by the central nervous system. It can manifest as acute or chronic pain. Pain is controlled by a series of enzymes and receptors, implicated in a variety of interconnected mechanisms and pathways. In fact, several studies have shown the cannabinoid receptor1 and the transient receptor potential vanilloid channel1 to be new players in modulating the sophisticated pain transduction system at the central level. At the peripheral level, the perception of pain involves cyclooxygenases and fatty acid amide hydrolase, as recent studies demonstrate. This Minireview describes the physiological aspects of the receptors and enzymes mentioned above and focuses on the consideration of dual mechanisms as a new therapeutic approach in the treatment of pain
Evaluation of the In Vitro Wound-Healing Activity of Calabrian Honeys
Full text linkThe healing of skin wounds and particularly chronic wounds, such as diabetic foot ulcers, is still a clinical emergency. Despite the many therapeutic tools that are available so far, none seems to be really effective and safe. In this context, we highlighted the renewed wound healing activity of honey, a viscous aromatic and sweet food, by way of in vitro wound-healing assays, using the HaCaT cell line. Specifically, we investigated five monofloral or multifloral honeys from different Calabrian provinces using them as such or extracted (by Amberlite® or n-hexane and ethyl acetate). The chemical composition of honeys was ascertained by 1H NMR spectroscopy and by the gas chromatography/mass spectrometry (GC/MS) method for volatile organic compounds (VOCs). Amongst the five tested honeys, BL1 and BL5 honeys showed the most promising healing properties. Pinocembrin, which was revealed in BL1 (multifloral) and BL5 (orange) honey samples, is a flavanol that is already known to possess interesting biological activities, including healing. This study aims to investigate how a traditional food such as honey, which is appreciated for its nutritional value and used in folk medicine, can be enhanced as an effective modern remedial to promote a multifaceted and safe healing activity for all skin wounds
Unlocking the potential of biostimulants in sustainable agriculture: Effect of wood distillate on the nutritional profiling of apples
Full text linkIn this work, we report the investigation of the effect of exposure of apple trees to the bioeffector wood distillate (WD), a plant biostimulant used for improving the nutritional profiling of crop plants. We measured the effect by evaluating the biochemical and nutritional profile of both pulps and skin of fruits. WD (0.2 %, v/v) was applied once a week by foliar application, from May 2023 until September 2023. The results indicate that the WD-treated apples have a significant increase in several analyzed parameters (i.e., phenols, flavonoids, tannins, total antioxidant power, sugars, pectin, free amino acids, and mineral element content), especially in the pulp. These data were also confirmed by NMR and LC-ESI-MS techniques. This study pointed out that WD could be a handy tool for the cultivation of fruit trees
Metalloenzyme Inhibitors against Zoonotic Infections: Focus on Leishmania and Schistosoma
No full textThe term “zoonosis” denotes diseases transmissible among vertebrate animals and humans. These diseases constitute a significant public health challenge, comprising 61% of human pathogens and causing an estimated 2.7 million deaths annually. Zoonoses not only affect human health but also impact animal welfare and economic stability, particularly in low- and middle-income nations. Leishmaniasis and schistosomiasis are two important neglected tropical diseases with a high prevalence in tropical and subtropical areas, imposing significant burdens on affected regions. Schistosomiasis, particularly rampant in sub-Saharan Africa, lacks alternative treatments to praziquantel, prompting concerns regarding parasite resistance. Similarly, leishmaniasis poses challenges with unsatisfactory treatments, urging the development of novel therapeutic strategies. Effective prevention demands a One Health approach, integrating diverse disciplines to enhance diagnostics and develop safer drugs. Metalloenzymes, involved in parasite biology and critical in different biological pathways, emerged in the last few years as useful drug targets for the treatment of human diseases. Herein we have reviewed recent reports on the discovery of inhibitors of metalloenzymes associated with zoonotic diseases like histone deacetylases (HDACs), carbonic anhydrase (CA), arginase, and heme-dependent enzyme
Quercetin-3-Oleoyl Derivatives as New GPR40 Agonists: Molecular Docking Studies and Functional Evaluation
No full textThe G-protein-coupled receptor 40 (GPR40) is an attractive molecular target for the treatment of type 2 diabetes mellitus. Previously, based on the natural oleic acid substrate, an exogenous ligand for this receptor, named AV1, was synthesized. In this context, here we validated the activity of AV1 as a full agonist, while the corresponding catechol analogue, named AV2, was investigated for the first time. The ligand-protein interaction between this new molecule and the receptor was highlighted in the lower portion of the GPR40 groove that generally accommodates DC260126. The functional assays performed have demonstrated that AV2 is a suitable GPR40 partial agonist, showing a therapeutic potential and representing a useful tool in the management of type 2 diabetes
FFAR1/GPR40: One target, different binding sites, many agonists, no drugs, but a continuous and unprofitable tug-of-war between ligand lipophilicity, activity, and toxicity
No full textThe progress made so far in the elucidation of the structure of free fatty acid receptor 1 (FFAR1) and its secondary
and ternary complexes with partial and full allosteric ligands led to the discovery of various putative
binding regions on the FFAR1 surface. Attempts to develop FFAR1 agonists culminated with the identification of
TAK-875 (1), whose phase 3 clinical trials were terminated due to potential liver toxicity. In the search of safer
agonists, numerous classes of new compounds were designed, synthesized, and tested. Chemical decoration of
the scaffolds was rationalized to reach a good balance between lipophilicity, activity, and toxicity. Today, targeting
FFAR1 with positive modulators represents an attractive pharmacological tool for the treatment of type 2
diabetes mellitus (T2DM), mainly because of the lack of hypoglycaemic side effects associated with several
antidiabetic drugs currently available. Moreover, considering the involvement of FFAR1 in many physiopathological
processes, its agonists are also emerging as possible therapeutic tools for alleviating organ
inflammation and fibrosis, as well as for the treatment of CNS disorders, such as Alzheimer’s disease and
dementia
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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