Thymus vulgaris Essential Oil and Hydro-Alcoholic Solutions to Counteract Wooden Artwork Microbial Colonization

Aromatic plants represent a source of natural products with medicinal properties, and are also utilized in the food and pharmaceutical industries. Recently, the need for eco-compatible and non-toxic products, safe for both the environment and human health, have been proposed for the sustainable conservation of historic–artistic artifacts. In this study, in order to counteract microbial colonization (Aspergillus sp., Streptomyces sp., Micrococcus sp.) on wooden artwork surfaces, Thymus vulgaris L. (Lamiaceae) essential oil (EO) and hydro-alcoholic (HA) solutions were applied in a polyphasic approach. The antimicrobial activities of EO and HA solutions were preliminarily assessed by agar disc diffusion (ADD) and well plate diffusion (WPD) in vitro methods, defining the specific concentration useful for bacterial and fungal genera, identified by optical microscopies, in vitro cultures (nutrient or Sabouraud agar), and DNA base molecular biology investigations. Specifically, the microbial patina was directly removed by a hydro-alcoholic solution (while evaluating the potential colorimetric change of the artwork’s surface) combined with exposure to EO volatile compounds, performed in a dedicated “clean chamber”. This study proposes, for the first time, the combined use of two plant extracts to counteract microbial development on wooden artworks, providing supplementary information on these products as bio-agents

Erratum to nodal management and upstaging of disease. Initial results from the Italian VATS Lobectomy Registry

[This corrects the article DOI: 10.21037/jtd.2017.06.12.]

Galactosylated Polymer/Gold Nanorods Nanocomposites for Sustained and Pulsed Chemo-Photothermal Treatments of Hepatocarcinoma

In this paper, we propose a rational design of a hybrid nanosystem capable of locally delivering a high amount of hydrophobic anticancer drugs (sorafenib or lenvatinib) and heat (hyperthermia) in a remote-controlled manner. We combined in a unique nanosystem the excellent NIR photothermal conversion of gold nanorods (AuNRs) with the ability of a specially designed galactosylated amphiphilic graft copolymer (PHEA-g-BIB-pButMA-g-PEG-GAL) able to recognize hepatic cells overexpressing the asialoglycoprotein receptor (ASGPR) on their membranes, thus giving rise to a smart composite nanosystem for the NIR-triggered chemo-phototherapy of hepatocarcinoma. In order to allow the internalization of AuNRs in the hydrophobic core of polymeric nanoparticles, AuNRs were coated with a thiolated fatty acid (12-mercaptododecanoic acid). The drug-loaded hybrid nanoparticles were prepared by the nanoprecipitation method, obtaining nanoparticles of about 200 nm and drug loadings of 9.0 and 5.4% w/w for sorafenib and lenvatinib, respectively. These multifunctional nanosystems have shown to convert NIR radiation into heat and release charged drugs in a remote-controlled manner. Then, the biocompatibility and synergistic effects of a chemo-phototherapy combination, as well the receptor-mediated internalization, were evaluated by an in vitro test on HepG2, HuH7, and NHDF. The results indicate that the proposed nanoparticles can be considered to be virtuous candidates for an efficient and selective dual-mode therapy of hepatocarcinoma

Polymeric platform for the growth of chemically anchored ZnO nanostructures by ALD

The synthesis of hybrid nano-composites in which an inorganic layer is grown on a polymeric surface via chemical bonds, is a challenging goal for many applications from photocatalysis, to sensing and optoelectronics

Antioxidant and neuroprotective properties of an aqueous dry extract from the S. officinale aerial parts

Sisymbrium officinale (L.) Scop. (syn. Erysimum officinale L., hedge mustard; Fam. Brassicaceae), is a medicinal plant used traditionally to relief respiratory system’s disorders, hence its “singers’ plant” name [1]. It has been found endowed with myorelaxant, antimicrobial, antimutagenic, antinflammatory and antioxidant activities, likely ascribed to the presence of glucosinolates (mainly glucoputranjivin and isopropyl isothiocyanate) and polyphenolic compounds [1,2]. Glucosinolates are also shown to possess promising chemopreventive and neuroprotective properties [3]. In line with this evidence, in the present study, we investigated the potential neuroprotective and antioxidant properties of an aqueous dry extract of the S. officinale aerial parts (EPO S.r.l.; standardized to contain 0.50% w/w glucosinolates), in brain cell models. To this end, murine Neuro-2a neuroblasts and human neuroblastoma SHSY-5Y cells were used. The protective effects were assessed towards the oxidative damage induced by hydrogen peroxide (H2O2), tert-butyl hydroperoxide (tBOOH) and amyloid beta peptide (Aβ). Preliminarily, the cytotoxicity of the extract (24 h exposure) was assayed by the MTT assay, to select the nontoxic concentrations to be tested for the cytoprotection; the intracellular concentration of the free peroxide and hydroxyl radicals was measured too [4,5]. Antioxidant in vitro assays, including FRAP (Ferric Reducing Antioxidant Potential), ORAC (Oxygen Radical Antioxidant Capacity), DPPH, xanthine/xanthine oxidase, along with the inhibition of central nervous system (CNS) enzymes (monoaminoxidase A, acetylcholinesterase, tyrosinase), known to be involved in neurodegenerative diseases have been also performed [4]. The extract’s tolerability was confirmed in the Artemia invertebrate model. A chemical characterization of the extract was obtained by derivatization followed by GC-MS (gas chromatography-mass spectrometry) analysis. The obtained results highlighted that the extract was able to prevent the oxidative stress induced by hydroperoxides in Neuro-2a neuroblasts and by Aβ protein in SHSY-5Y cells. However, mitochondrial activity and cell viability of Neuro2a cells were not affected by the treatments. The S. officinale extract has also shown an antioxidant capacity against the free radical DPPH and superoxide anions generated by xanthine/xanthine oxidase (X/X.O.) system, almost reaching and overcoming, respectively, the percentage of inhibition exerted by the standard antioxidant compounds. 1° Congresso intersocietà sui prodotti vegetali per la salute: Il ruolo delle piante medicinali nella medicina moderna PADOVA, 15-17 Giugno 2023 Dipartimento di Scienze del Farmaco, Via Marzolo, 5 Conversely, weak, or null inhibitory effects were highlighted against CNS enzymes, compared to the reference compounds. At last, the extract showed to be well tolerated up to the concentration of 500 μg/ml in the Artemia invertebrate assay. At the phytochemical analysis, the extract revealed the presence of a rich phytocomplex, characterized by alcohols, sugars, fatty acids and carboxylic acids. Altogether, the obtained results highlighted the tested S. officinale extract is a source of bioactive compounds with potential neuroprotective properties. Further studies could allow to clarify the role of phenolic compounds and glucosinolates in S. officinale bioactivities, to develop improved standardized extracts to be exploit for neuroprotective purposes and to confirm these activities in vivo. References 1. Di Sotto et al. Journal of Ethnopharmacology 2010, 127, 731–736. 2. Di Sotto et al. Phytotherapy research 2016, 30, 829–834. 3. Borgonovo et al. Molecules 2019, 24(24). 4. Cásedas et al. Food and Chemical Toxicolog

Valorisation of an Italian mountain variety of Echinacea purpurea (L.) Moench: a sustainable strategy for medicinal plant production

Background: Medicinal plants are exploited worldwide as traditional remedies and as ingredients of nutraceuticals and dietary supplements [1]. Their production has been limited, due climate change and environmental pollution, leading to the risk of biodiversity extinction [2]. Therefore, different conservation and sustainable strategies has been approached to retain plant biodiversity [1,2]. In the present study an Italian mountain variety of Echinacea purpurea (L.) Moench, grown in the south-western of Trentino, has been evaluated for the phytochemical composition and bioactivities. The interest in this species arises from its countless properties [3] and the increased demand due to the outbreak of Covid-19. Methods: A dry extract from aerial parts of Italian mountain variety of Echinacea purpurea (L.) Moench (namely ECH), prepared and provided by EPO Srl (Milan, Italy), has been studied and compared with a similar extract (EC), obtained from commercial echinacea varieties. Total polyphenols, tannins and flavonoids, along with phenolic composition were determined [4]. A bioactivity screening, including radical scavenging, antiglicative, cytoprotective, antiviral and immunomodulating ones, was performed too [4]. To this end, BEAS-2B (human bronchial epithelial cells), A549 (human lung cancer cells), and murine macrophages RAW 264.7, were used. The cytoprotective effects were evaluated towards damage induced by tert-butyl hydroperoxide and lipopolysaccharides (LPS from Escherichia coli O111:B4). Results: ECH contained higher levels of total polyphenols, tannins and flavonoids respect to EC samples; however, the samples exhibited similar radical scavenging, chelating and antiglycative activity. HPLC analysis showed chicoric acid, caftaric acid, and 2-hydroxytyrosol as the major compounds, which were especially abundant in ECH sample. Despite a low cytoprotection towards damage induced by tBOOH, the extracts stimulated RAW 264.7 macrophages and to counteract nitric oxide secretion induced by LPS. Conversely, antiviral effects were weak or lacking. Present findings highlight interesting antioxidant, immunomodulating and anti-inflammatory properties of ECH, in line with those of EC. Moreover, the marked content of chicoric acid, caftaric acid, and 2-hydroxytyrosol suggest possible peculiar properties which deserves further studies. Conclusions: Present findings encourage the production of this local variety of echinacea, which could be of interest in pharmaceutical/ nutraceutical fields, with positive relapse on the market of medicinal plants and on local economy. References [1] Chen et al. Chin Med. 2016,11,37. [2] Applequist et al. Planta Med. 2020,86,10-18. [3] EMA/HMPC/557979/2013 e EMA/HMPC/424584/2016 [4] Di Sotto et al. Oxid Med Cell Longev. 2018, 2018,5919237

Pharmacological targeting of the novel β-catenin chromatin-associated kinase p38α in colorectal cancer stem cell tumorspheres and organoids

The prognosis of locally advanced colorectal cancer (CRC) is currently unsatisfactory. This is mainly due to drug resistance, recurrence, and subsequent metastatic dissemination, which are sustained by the cancer stem cell (CSC) population. The main driver of the CSC gene expression program is Wnt signaling, and previous reports indicate that Wnt3a can activate p38 MAPK. Besides, p38 was shown to feed into the canonical Wnt/beta-catenin pathway. Here we show that patient-derived locally advanced CRC stem cells (CRC-SCs) are characterized by increased expression of p38alpha and are "addicted" to its kinase activity. Of note, we found that stage III CRC patients with high p38alpha levels display reduced disease-free and progression-free survival. Extensive molecular analysis in patient-derived CRC-SC tumorspheres and APCMin/+ mice intestinal organoids revealed that p38alpha acts as a beta-catenin chromatin-associated kinase required for the regulation of a signaling platform involved in tumor proliferation, metastatic dissemination, and chemoresistance in these CRC model systems. In particular, the p38alpha kinase inhibitor ralimetinib, which has already entered clinical trials, promoted sensitization of patient-derived CRC-SCs to chemotherapeutic agents commonly used for CRC treatment and showed a synthetic lethality effect when used in combination with the MEK1 inhibitor trametinib. Taken together, these results suggest that p38alpha may be targeted in CSCs to devise new personalized CRC treatment strategies