The Purinergic System as a Pharmacological Target for the Treatment of Immune-Mediated Inflammatory Diseases

Immune-mediated inflammatory diseases (IMIDs) encompass a wide range of seemingly unrelated conditions, such as multiple sclerosis, rheumatoid arthritis, psoriasis, inflammatory bowel diseases, asthma, chronic obstructive pulmonary disease, and systemic lupus erythematosus. Despite differing etiologies, these diseases share common inflammatory pathways, which lead to damage in primary target organs and frequently to a plethora of systemic effects as well. The purinergic signaling complex comprising extracellular nucleotides and nucleosides and their receptors, the P2 and P1 purinergic receptors, respectively, as well as catabolic enzymes and nucleoside transporters is a major regulatory system in the body. The purinergic signaling complex can regulate the development and course of IMIDs. Here we provide a comprehensive review on the role of purinergic signaling in controlling immunity, inflammation, and organ function in IMIDs. In addition, we discuss the possible therapeutic applications of drugs acting on purinergic pathways, which have been entering clinical development, to manage patients suffering from IMIDs

Desenvolvimento de um portal colaborativo da Sustentabilidade da Cana-de-Açúcar e oja na Região Centro-Sul.

Este trabalho apresenta a criação do portal do SustenAgro criado no ambiente da Agropedia brasilis, a partir da criação de uma organização onde serão adicionados os membros da equipe do projeto e suas respectivas permissões

Dietary Supplement, Containing the Dry Extract of Curcumin, Emblica and Cassia, Counteracts Intestinal Inflammation and Enteric Dysmotility Associated with Obesity

Intestinal epithelial barrier (IEB) impairment and enteric inflammation are involved in the onset of obesity and gut-related dysmotility. Dietary supplementation with natural plant extracts represents a useful strategy for the management of body weight gain and systemic inflammation associated with obesity. Here, we evaluate the efficacy of a food supplement containing the dry extract of Curcumin, Emblica and Cassia in counteracting enteric inflammation and motor abnormalities in a mouse model of obesity, induced by a high-fat diet (HFD). Male C57BL/6 mice, fed with standard diet (SD) or HFD, were treated with a natural mixture (Curcumin, Emblica and Cassia). After 8 weeks, body weight, BMI, liver and spleen weight, along with metabolic parameters and colonic motor activity were evaluated. Additionally, plasma LBP, fecal calprotectin, colonic levels of MPO and IL-1β, as well as the expression of occludin, TLR-4, MYD88 and NF-κB were investigated. Plant-based food supplement administration (1) counteracted the increase in body weight, BMI and metabolic parameters, along with a reduction in spleen and liver weight; (2) showed strengthening effects on the IEB integrity; and (3) reduced enteric inflammation and oxidative stress, as well as ameliorated the colonic contractile dysfunctions. Natural mixture administration reduced intestinal inflammation and counteracted the intestinal motor dysfunction associated with obesity

MIS 5.5 highstand and future sea level flooding at 2100 and 2300 in tectonically stable areas of central mediterranean sea: Sardinia and the pontina plain (Southern Latium), Italy

Areas of the Mediterranean Sea are dynamic habitats in which human activities have been conducted for centuries and which feature micro-tidal environments with about 0.40 m of range. For this reason, human settlements are still concentrated along a narrow coastline strip, where any change in the sea level and coastal dynamics may impact anthropic activities. We analyzed light detection and ranging (LiDAR) and Copernicus Earth observation data. The aim of this research is to provide estimates and detailed maps (in three coastal plain of Sardinia (Italy) and in the Pontina Plain (southern Latium, Italy) of: (i) the past marine transgression occurred during MIS 5.5 highstand 119 kyrss BP; (ii) the coastline regression occurred during the last glacial maximum MIS 2 (21.5 krs cal BP); and (iii) the potential marine submersion for 2100 and 2300. The objective of this multidisciplinary study is to provide maps of sea level rise future scenarios using the IPCC RCP 8.5 2019 projections and glacio-hydro-isostatic movements for the above selected coastal zones (considered tectonically stable), which are the locations of touristic resorts, railways and heritage sites. We estimated a potential loss of land for the above areas of between about 146 km(2) (IPCC 2019-RCP8.5 scenario) and 637 km(2) along a coastline length of about 268 km

Preparation and Properties of PTFE-PMMA Core-Shell Nanoparticles and Nanocomposites

he preparation of polytetrafluoroethylene-poly(methyl methacrylate) (PTFE-PMMA) core-shell particles was described, featuring controlled size and narrow size distribution over a wide compositional range, through a seeded emulsion polymerization starting from a PTFE seed of 26 nanometers. Over the entire MMA/PTFE range, the particle size increases as the MMA/PTFE ratio increases. A very precise control over the particle size can be exerted by properly adjusting the ratio between the monomer and the PTFE seed. Particles in the 80240 nm range can be prepared with uniformity indexes suited to build 2D and 3D colloidal crystals. These core-shell particles were employed to prepare nanocomposites with different compositions, through an annealing procedure at a temperature higher than the glass transition temperature of the shell forming polymer. A perfect dispersion of the PTFE particles within the PMMA matrix was obtained and optically transparent nanocomposites were prepared containing a very high PTFE amount

Adverse reactions to oncologic drugs: spontaneous reporting and signal detection

Oncology is one of the areas of medicine with the most active research being conducted on new drugs. New pharmacological entities frequently enter the clinical arena, and therefore, the safety profile of anticancer products deserves continuous monitoring. However, only very severe and (unusual) suspected adverse drug reactions (ADRs) are usually reported, since cancer patients develop ADRs very frequently and some practical selectivity must be used. Notably, a recent study was able to identify 76 serious ADRs reported in updated drug labels of oncologic drugs and 50% of them (n = 38) were potentially fatal. Of these, 49 and 58%, respectively, were not described in initial drug labels. The aims of this article are to provide an overview about spontaneous reporting of ADRs of oncologic drugs and to discuss the available methods to analyze the safety of anticancer drugs using databases of spontaneous ADR reporting

Preclinical and clinical aspects of P2X receptors as a common route in different diseases: a meeting report

PRESTO was established in 2022 and is a concerted effort by leading European experts in the field of P2XRs and extracellular ATP to promote and advance the transition to the clinic of P2XR-targeting therapies. Following the inaugural meeting in Ferrara which set the foundations of the action and generated interest from many groups and institutes, the second meeting covered the preclinical and clinical aspects of P2XRs as a common route in different diseases, recognising the multidisciplinary and collaborative approach required for a number of medical conditions

AMPK Activators as Novel Drug Candidates for the Treatment of Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBDs), mainly represented by ulcerative colitis and Crohn’s disease, are chronic and idiopathic diseases of the digestive tract. They incidence and prevalence is raising significantly in both developed and developing countries, thus representing a major challenge for the worldwide healthcare systems. The pharmacological armamentarium for the treatment of IBDs is far from being satisfactory, as the therapeutic success of the available drugs is still limited. Accordingly, the development of novel and effective compounds is highly requested. In this context, the serine/threonine heterotrimeric kinase AMPK (adenosine monophosphate-activated protein kinase) seems a sound target to strike. Known as the central hub of energy homeostasis in eukaryotic cells, AMPK contributes also to the modulation of immune/inflammatory cell functions. Actually, alterations in AMPK expression and/or activity play a key role in the pathophysiology of immune-mediated inflammatory diseases characterized by abnormal immune cell functions, like IBDs. Moreover, AMPK is able to improve intestinal health by enhancing para-cellular junctions, nutrient transporters, autophagy and apoptosis. Accordingly, AMPK activation represents a promising therapeutic strategy for the treatment of intestinal inflammatory disorders. Here we describe a novel heterocyclic derivative, developed as AMPK activator. Tested in C2C12 myoblast cell lines, our compound significantly increased AMPK activity, in a concentration-dependent manner, turning out to be more effective than the well-known activator acadesine (ACA). Moreover, assayed in a mouse model of acute DNBS-induced colitis, the novel heterocycle displayed a relevant anti-inflammatory efficacy, proving to ameliorate both systemic- and tissue-related inflammatory parameters like body and spleen weight, colon length, macroscopic damage, TNF and MDA levels. Also in this case, our compound turned out to be significantly more active that the known reference ACA, thus imposing itself as a novel and valuable drug candidate for the treatment of IBDs

On the rehydration of organic layered double hydroxides to form low-ordered carbon/LDH nanocomposites

Low-ordered carbon/layered double hydroxide (LDH) nanocomposites were prepared by rehydration of the oxides produced by calcination of an organic LDH. While the memory effect is a widely recognized effect on oxides produced by inorganic LDH, it is unprecedented from the calcination/rehydration of organic ones. Different temperatures (400, 600, and 1100 °C) were tested on the basis of thermogravimetric data. Water, instead of a carbonate solution, was used for the rehydration, with CO2 available from water itself and/or air to induce a slower process with an easier and better intercalation of the carbonaceous species. The samples were characterized by X-ray powder diffraction (XRPD), infrared in reflection mode (IR), and Raman spectroscopies and scanning electron microscopy (SEM). XRPD indicated the presence of carbonate LDH, and of residuals of unreacted oxides. IR confirmed that the prevailing anion is carbonate, coming from the water used for the rehydration and/or air. Raman data indicated the presence of low-ordered carbonaceous species moieties and SEM and XRPD the absence of separated bulky graphitic sheets, suggesting an intimate mixing of the low ordered carbonaceous phase with reconstructed LDH. Organic LDH gave better memory effect after calcination at 400 °C. Conversely, the carbonaceous species are observed after rehydration of the sample calcined at 600 °C with a reduced memory effect, demonstrating the interference of the carbonaceous phase with LDH reconstruction and the bonding with LDH layers to form a low-ordered carbon/LDH nanocomposite