YAP/TAZ functions and their regulation at a glance

YAP and TAZ proteins are paralog transcriptional coactivators that shuttle between the cytoplasm and the nucleus in response to multiple inputs, including the Hippo pathway; in the nucleus, they pair with DNA-binding factors of the TEAD family to regulate gene expression. Nuclear YAP/TAZ promote cell proliferation, organ overgrowth, survival to stress and dedifferentiation of post-mitotic cells into their respective tissue progenitors. YAP/TAZ are required for growth of embryonic tissues, wound healing and organ regeneration, where they are activated by cell-intrinsic and extrinsic cues. Surprisingly, this activity is dispensable in many adult self-renewing tissues, where YAP/TAZ are constantly kept in check. YAP/TAZ lay at the center of a complex regulatory network including cell-autonomous factors but also cell- and tissue-level structural features such as the mechanical properties of the cell microenvironment, the establishment of cell-cell junctions and of basolateral tissue polarity. Enhanced levels and activity of YAP/TAZ are observed in many cancers, where they sustain tumour growth, drug resistance and malignancy. In this Cell science at a glance and the accompanying poster, we review the biological functions of YAP/TAZ and their regulatory mechanisms, and highlight their position at the center of a complex signaling network

Exploiting Extracellular Vesicles Strategies to Modulate Cell Death and Inflammation in COVID-19

The coronavirus disease (COVID-19) is responsible for more than 5 million deaths worldwide, with respiratory failure being the most common clinical presentation. COVID-19 complications still present a considerable burden on healthcare systems, and signs of the post-COVID syndrome are concerns for potential long-term damages. An increasing body of evidence highlights extracellular vesicles' (EVs) relevance in modulating inflammation and cell death in the diseases related to these processes. Several types of EVs-based investigational new drugs against COVID-19 have been approved by the US Food and Drug Administration to initiate a Phase I/II trial under an Investigational New Drug protocol. EVs can be employed as natural drug delivery nanoparticle-based systems due to their inherent potential in transferring material between cells, their natural origin, and their capability to encapsulate various biological molecules, offering an exciting alternative for administering drugs acting on the cell cycle control. In this context, small-molecule inhibitors of Mouse Double Minute 2 (MDM2) such as Nutlin-3 and Idasanutlin by promoting p53 survival and its antiviral activity might be helpful to modulate the IFN signalling pathway and reduce the overall pro-inflammatory burden

Circular Economy as a New Model for the Exploitation of the Agroindustrial Biomass

This paper focuses on a new concept of waste and by-products within the agricultural system, based upon the perspective of circular economy, which directs the agrifood chain and the life style towards a "zero waste" model. This new approach can be achieved through efficient small and industrial scale of bioenergy plants, biorefineries and environmentally friendly process for the production of biomolecules to be employed as active principles in agronomy, cosmetics, foods, feeds and pharmaceutical applications. In particular, the case study of this paper concerns the exploitation of Olea, Cynara and Chestnut tissues and byproducts as new source for energy and bioactive antioxidant and antimicrobial compounds (polyphenols) (PCT/IT/2009/09425529 Olea europaea L.; PCT/IT/2008/000135 Cynara scolymus L., MI2014A000177 Chestnut), which will also be assessed in different Italian district. The regional level has been chosen for this analysis because the local approach allows to avoid and/or reduce the economic and environmental cost of the waste transport. The polyphenols market is projected to reach 1 billion dollars by 2020 and 4,790 potential source plants are present in Europe. The recovery of chemicals and the production of energy, should be a continuous process of interaction between high technology and environmental and economic sustainability, making this kind of multifunctional platform highly innovative and consistent with the principles of the circular econom

Quality control and analytical test method for Taxus baccata tincture preparation.

The homeopathic tincture of Taxus baccata L. is monographed in the current German Homeopathic Pharmacopoeia (HAB 2009). However, the described identification test is a common comparative TLC procedure that might be updated. The purpose of the current work was the quali-quantitative analysis by HPLC/DAD/MS of Taxus tincture. In this study we characterized polyphenolic compounds, in particular four hydroxycinnamic derivatives (0.85 mg/mL) and four flavonoids (quercetin and kaempferol 3- O-rutinoside and xylosyl glucosides); the total polyphenol content was 1.265 mg/mL of tincture. Starting from the official German Homeopathic Pharmacopoeia method of preparation, the aim of this work was to optimize a rapid and reproducible method for the analysis of herbal drugs and tincture, directly prepared in store or the herbalist's shop, to ensure safety and efficacy of the preparation. The procedure has to ensure validation, robustness of the results, and provide a quick response about the composition of compounds in the herbal drug preparation

Monitoring water fluxes in rice plots under three different cultivation methods

Italy is the leading producer of rice in Europe with over half of total production, almost totally concentrated in a large traditional paddy rice area between the Lombardy and Piedmont regions, in the north-western part of the country. In this area irrigation of rice has been traditionally carried out by flooding. The introduction of new combined irrigation and agronomic management practices (dry seeding followed by field flooding and in a full aerobic cultivation with intermittent irrigations), aiming to reduce the water consumption, can determine considerable effect on the landscape and the water cycle. With the aim to study in depth the water fluxes during the whole crop season, three experimental plots at the Ente Nazionale Risi-Rice Research Centre’s Experimental Station of Castello d’Agogna (PV) were instrumented. In each plot the following instruments have been installed: 1) a long throated flume and a double shaped (V-notch and rectangular) thin plate for superficial inputs and outputs, 3) a set of piezometers for groundwater levels, 4) one stage level gauge in each submerged field, 5) four tensiometers and moisture sensors clusters, 6) one eddy covariance station for vapour fluxes estimation. Most of the instruments were equipped with electrical sensors connected by cables to a wireless data logger that, in turn, send the data to a PC placed within ENR offices and web-connected by a LAN. In this way, besides the automatic download of data, it was possible to remotely control the devices, to quickly fix troubles, and to better plan the field trips. The management of the whole framework was done by a specifically developed software. In this paper the whole system, which presents some degree of innovation, is described in detail

Nutrients, herbal bioactive derivatives and commensal microbiota as tools to lower the risk of SARS-CoV-2 infection

The SARS-CoV-2 outbreak has infected a vast population across the world, causing more than 664 million cases and 6.7 million deaths by January 2023. Vaccination has been effective in reducing the most critical aftermath of this infection, but some issues are still present regarding re-infection prevention, effectiveness against variants, vaccine hesitancy and worldwide accessibility. Moreover, although several old and new antiviral drugs have been tested, we still lack robust and specific treatment modalities. It appears of utmost importance, facing this continuously growing pandemic, to focus on alternative practices grounded on firm scientific bases. In this article, we aim to outline a rigorous scientific background and propose complementary nutritional tools useful toward containment, and ultimately control, of SARS-CoV-2 infection. In particular, we review the mechanisms of viral entry and discuss the role of polyunsaturated fatty acids derived from α-linolenic acid and other nutrients in preventing the interaction of SARS-CoV-2 with its entry gateways. In a similar way, we analyze in detail the role of herbal-derived pharmacological compounds and specific microbial strains or microbial-derived polypeptides in the prevention of SARS-CoV-2 entry. In addition, we highlight the role of probiotics, nutrients and herbal-derived compounds in stimulating the immunity response

Oleuropein, the Main Polyphenol of Olea europaea Leaf Extract, Has an Anti-Cancer Effect on Human BRAF Melanoma Cells and Potentiates the Cytotoxicity of Current Chemotherapies

Oleuropein (Ole), a secoiridoid glucoside present in Olea europaea leaves, gained scientific interest thanks to its several biological properties, including the anticancer one. We verified whether Ole might potentiate the cytotoxicity of conventional drugs used to treat melanoma, disclosing a potentially new therapeutic strategy. We tested the cytotoxic action of Ole alone or in combination with chemotherapeutics on A375 human melanoma cells. We found that Ole was able, at a dose of 500 µM, to stimulate apoptosis, while at a non-toxic dose of 250 µM, it affected cell proliferation and induced the downregulation of the pAKT/pS6 pathway. A dose of 250 µM Ole did not potentiate the effect of Vemurafenib (PLX4032), but it succeeded in increasing the cytotoxic effect of Dacarbazine (DTIC). The major effect was found in the association between Ole and Everolimus (RAD001), also on PLX4032-resistant BRAF melanoma cells, which possibly cooperate in the inhibition of the pAKT/pS6 pathway. Of interest, an olive leaf extract enriched in equimolar Ole was more effective and able to further improve DTIC and RAD001 efficacy on BRAF melanoma cells with respect to Ole alone. Therefore, Ole represents a natural product able to potentiate a wide array of chemotherapeutics against BRAF melanoma cells affecting the pAKT/pS6 pathway