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Objective: Colon adenocarcinoma is characterized by the downregulation of the retinoic acid receptor, making natural retinoids such as all-trans retinoic acid, 9-cis retinoic acid and 13-cis retinoic acid effective in treatment and chemoprevention due to their ability to increase RARβ expression. However, major limitations to their use include tolerability and acquired resistance. In this study, we evaluated fenretinide, a semisynthetic derivative of all-trans retinoic acid, in an HT-29 cell line. Fenretinide was evaluated both as a free drug and encapsulated in self-assembling phosphatidylcholine nanosystems with the aim of increasing the aqueous solubility and cell availability of the drug. Methods: Fenretinide was encapsulated in lipid nanosystems obtained in water by the dispersion of an amphiphilic mixture of phospholipids, glyceryl tributyrate and polysorbate 80. The physico-chemical characterization of the nanosystems was carried out by dynamic light scattering and spectrophotometry. The biological activity was evaluated by quantitative phase imaging microscopy, MTT assay, flow cytometry and confocal laser-scanning fluorescence microscopy. Results: Fenretinide in phosphatidylcholine nanosystems was more active than free fenretinide in inhibiting HT-29 cells’ proliferation, as indicated by quantitative phase imaging data. Indeed, encapsulated fenretinide increased duplication time, decreased dry mass and decreased the rate of cell growth more efficiently than fenretinide. Moreover, encapsulated fenretinide effectively decreased the motility of the cells that survived the treatment. Conclusions: The results indicate that the proposed nanosystems can be considered a valuable alternative to natural retinoids in the chemoprevention and treatment of colorectal cancer. This is due to the favorable pharmacologic characteristics of fenretinide in colorectal cancer and the improved drug activity provided by nanoencapsulation.

Rosemary (Rosmarinus officinalis L.) is an evergreen and a xerophytic shrub that is frequently employed in culinary, decorative, and industrial applications. It shows significant variations in biomass and essential oil (EO) yield due to effects of biotic and abiotic factors. Biostimulants are widely used in agriculture, and in organic agricultural systems, they may contribute significantly to the stability and/or to the increase in crop yields, ensuring respect for the environment. The aim of this study was to assess the effect of different types of biostimulants on the yield performance of rosemary. Four commercial formulations of biostimulants based on Eklonia maxima, Ascophyllum nodosum, fulvic acids, and protein hydrolysates were used for the tests. Water was used as a control. Six applications were performed. At harvest, several morphological and productive parameters were determined. All parameters were affected by biostimulant application. The highest fresh and dry yields were obtained with the application of fulvic acids (13.1 t ha−1 of fresh biomass and 4.3 t ha−1 of dry biomass) and protein hydrolysates (13.6 t ha−1 of fresh biomass and 4.4 t ha−1 of dry biomass) with values 60% higher than that of the control. Regarding the EO content in the dry biomass, the highest value (1.72% v/w) was found in control plants, whilst the lowest (1.14%) was observed in plants treated with fulvic acids. In the case of the EO yield, the lowest value (46.5 kg ha−1) per unit area was found in the control. The application of Eklonia maxima and protein hydrolysates produced the highest EO yield values, 65 kg ha−1 and 66.5 kg ha−1, respectively. This study highlights the use of biostimulants to increase the yield performance of rosemary when grown in an organic agricultural system.

γ-terpinene, α-terpinene, p-cymene, and myrcene are monoterpenes found in many essential oils extracted from a variety of plants and spices. Myrcene also occurs naturally in plants such as hops, cannabis, lemongrass, and verbena and is used as a flavoring agent in food and beverage manufacturing. In this research, the biological efficacy of γ-terpinene, α-terpinene, p-cymene, and myrcene was studied in human cell lines (HeLa, SH-SY5Y, and HDFa). Cytotoxicity, cell proliferation, cell migration, and morphology assays were performed to obtain detailed information on the anticancer properties. Our results show that myrcene has potential biological activity, especially in HeLa cells. In this cell line, it leads to an arrest of proliferation, a decrease in motility and morphological changes with loss of sphericity and thickness, and DNA damage. In addition, the interaction of γ-terpinene, α-terpinene, p-terpinene, and myrcene with calf thymus DNA (ct-DNA) was studied by UV-visible spectrophotometry. DNA binding experiments show that only myrcene can interact with DNA with an apparent dissociation constant (Kd) of 29 × 10−6 M.

The vegetative propagation of hops, despite being a reliable method, is not very common due to the unavailability of the plant material. In this study, the technique of in vitro propagation was applied to the Cascade variety of Humulus lupulus L. The plant material was collected from a private field in Sicily; the explants were subjected to sterilization before in vitro culture. Single-node explants were placed in in vitro culture in nine different culture media for multiplication. Thidiazuron (TDZ), Benzyladenine (BAP) and meta-Topoline (mT) were tested for multiplication phase. For the rooting phase, five types of different culture media were evaluated. Binodal cuttings coming from the previous multiplication test were placed in the culture. The rooting media differ from each other in the concentration and ratio of two auxin hormones: Indolo-3-acetic acid (IAA) and Indole-3-butyric acid (IBA). In vitro rooted plants obtained from the rooting phase were transferred to ex vitro conditions in a microbox with agri-perlite and a solution containing Murashige and Skoog (MS) basal medium at half concentration. With a culture medium containing the highest TDZ doses (H6) and combination with cytokinin (H8 and H9), the highest shoot percentage was obtained. After 3 months of in vitro culture, the highest shoot percentage was observed in the culture medium with 2 mL L−1 of BAP. The highest rooting percentage, roots numbers and root length were found when the culture medium was supplemented with 1 mL L−1 of IAA. The usage of agri-perlite and MS at half concentration, without PGR, allowed us to obtain a 99.1% survival rate. This micropropagation protocol is useful for obtaining virus-free plants and for the development of the brewery industry.

Anaplastic large cell lymphoma (ALCL) is a histological subtype of non-Hodgkin lymphoma, largely characterized by anaplastic lymphoma kinase (ALK) positivity, resulting from the chromosomal translocation t(2;5). We report a pediatric case of ALK-positive ALCL with primary concomitant involvement of bone and central nervous system (CNS); thereafter, a literature review about pediatric primary bone and primary CNS ALCL was conducted. According to the analyzed data, our case is unique because it is characterized by the contemporary involvement of the spine and CNS. During and after chemotherapy, our patient was monitored by detecting minimal residual disease (MRD) through the analysis of fusion transcript nucleophosmin-ALK. MRD assessment, not only in bone marrow but also in peripheral blood, seems to be a very powerful tool for predicting the prognosis of pediatric ALCL patients, as already described in the literature. Moreover, as shown in our case, it could be used during the follow-up for early recognition of relapse.

Several studies have examined the prognostic performance of therapeutic groups (TG) and early responses to therapy on positron emission tomography/computed tomography (PET/CT) in children and adolescents with classical Hodgkin lymphoma (cHL); less research has been performed on molecular parameters at diagnosis. The aim of the present study was to devise a scoring system based on the TG criteria for predicting freedom from progression (FFP) in 133 patients: 63.2% males; 14 years median age (interquartile range (IQR) 11.9–15.1); with cHL (108 nodular sclerosis (NS) subtype) treated according to the AIEOP LH-2004 protocol; and median 5.55 (IQR 4.09–7.93) years of follow-up. CHL progressed or relapsed in 37 patients (27.8%), the median FFP was 0.89 years (IQR = 0.59–1.54), and 14 patients (10.5%) died. The FPR (final prognostic rank) model associates the biological HLA-G SNP 3027C/A (numerical point assigned (pt) = 1) and absolute neutrophil count (>8 × 109/L, pt = 2) as variables with the TG (TG3, pt = 3). Results of FPR score analyses for FFP suggested that FPR model (Kaplan–Meier curves, log-rank test for trends) was better than the TG model. At diagnosis, high-risk patients classified at FPR rank 4 and 5 identified 18/22 patients who relapse during the follow-up.

Metallodrugs represent a combination of multifunctionalities that are present concomitantly and can act differently on diverse biotargets. Their efficacy is often related to the lipophilic features exhibited both by long carbo-chains and the phosphine ligands. Three Ru(II) complexes containing hydroxy stearic acids (HSAs) were successfully synthesized in order to evaluate possible synergistic effects between the known antitumor activity of HSA bio-ligands and the metal center. HSAs were reacted with [Ru(H)2CO(PPh3)3] selectively affording O,O-carboxy bidentate complexes. The organometallic species were fully characterized spectroscopically using ESI-MS, IR, UV-Vis, and NMR techniques. The structure of the compound Ru-12-HSA was also determined using single crystal X-ray diffraction. The biological potency of ruthenium complexes (Ru-7-HSA, Ru-9-HSA, and Ru-12-HSA) was studied on human primary cell lines (HT29, HeLa, and IGROV1). To obtain detailed information about anticancer properties, tests for cytotoxicity, cell proliferation, and DNA damage were performed. The results demonstrate that the new ruthenium complexes, Ru-7-HSA and Ru-9-HSA, possess biological activity. Furthermore, we observed that the Ru-9-HSA complex shows increased antitumor activity on colon cancer cells, HT29.

Rising environmental awareness drives green consumers to purchase sustainable cosmetics based on natural bioactive compounds. The aim of this study was to deliver Rosa canina L. extract as a botanical ingredient in an anti-aging gel using an eco-friendly approach. Rosehip extract was first characterized in terms of its antioxidant activity through a DPPH assay and ROS reduction test and then encapsulated in ethosomal vesicles with different percentages of ethanol. All formulations were characterized in terms of size, polydispersity, zeta potential, and entrapment efficiency. Release and skin penetration/permeation data were obtained through in vitro studies, and cell viability was assessed using an MTT assay on WS1 fibroblasts. Finally, ethosomes were incorporated in hyaluronic gels (1% or 2% w/v) to facilitate skin application, and rheological properties were studied. Rosehip extract (1 mg/mL) revealed a high antioxidant activity and was successfully encapsulated in ethosomes containing 30% ethanol, having small sizes (225.4 ± 7.0 nm), low polydispersity (0.26 ± 0.02), and good entrapment efficiency (93.41 ± 5.30%). This formulation incorporated in a hyaluronic gel 1% w/v showed an optimal pH for skin application (5.6 ± 0.2), good spreadability, and stability over 60 days at 4 °C. Considering sustainable ingredients and eco-friendly manufacturing technology, the ethosomal gel of rosehip extract could be an innovative and green anti-aging skincare product.

Safflower (Carthamus tinctorius L.) is a promising oilseed crop for cultivation in central Southern Italy due to its high tolerance to drought and salinity stress and appreciable seed and oil yields. The genetic diversity of cultivars and climate factors can affect fatty acid composition and yield traits. This study aimed to assess the effects of genotype and climate conditions on the productive performance of eight high oleic safflower genotypes under rainfed conditions in Sicily (Italy). These genotypes were compared to the Montola 2000 cultivar, which was used as a reference. Tests were carried out during the growing seasons of 2014–2015 and 2015–2016. The experimental design was a randomized complete block design with three replications. Morphological and yield components were significantly affected by genotype while the year had a significant effect on plant height only. In general, CTI 17 produced the highest seed yield (1.40 t ha−1) and oil yield (0.58 t ha−1). The seed oil content was found on 40.2% of dry matter, on average. The “genotype” factor significantly affected oil content and fatty acid composition. Oleic acid content was on average 66.1% and did not vary greatly over the two growing seasons. The above- and belowground plant parts showed the highest carbon content and the lowest nitrogen content as a percentage of dry matter. The results indicate that, under rainfed conditions, yield parameters of high oleic safflower genotypes can be profitable in southern Italy though significantly dependent upon genotype.

Oregano, Origanum vulgare L., is a perennial herbaceous plant belonging to the Lamiaceae family. Oregano shows variations in biomass yield and essential oil (EO) content due to the influence of abiotic and biotic factors. The aim of this study was to assess the effect of different foliar applications based on calcium (Ca) and nitrogen (N) on morphological and productive parameters in oregano. Tests were carried out in Sicily (Italy) in 2020–2021. In each year, eight foliar applications were applied. Only flowers and leaves were used for the extraction of the EO. For all parameters in the study, except for plant height and inflorescence length, the highest values were found in treated plants with respect to the control. In plants treated with calcium and nitrogen, an increase of between 0.6 and 1.6 t ha−1 was observed for fresh yield, and an increase of between 0.5 and 0.9 t ha−1 was observed for dry yield. The increase in biomass yield led to an increase in EO yield of between 4 and 12 kg ha−1. The results highlight that foliar treatments with Ca in combination with N enable growth in crop production in environments that show poor water availability.

Neuroblastoma cells highly express the disialoganglioside GD2, a tumor-associated carbohydrate antigen, which is also expressed in neurons, skin melanocytes, and peripheral nerve fibers. Immunotherapy with monoclonal anti-GD2 antibodies has a proven efficacy in clinical trials and is included in the standard treatment for children with high-risk neuroblastoma. However, the strong neuro-toxicity associated with anti-GD2 antibodies administration has hindered, until now, the possibility for dose-escalation and protracted use, thus restraining their therapeutic potential. Strategies to increase the efficacy of anti-GD2 antibodies are actively sought, with the aim to enable chronic treatments that could eradicate minimal residual disease and subsequent relapses, often occurring after treatment. Here, we report that Nanofenretinide and Nanospermidine improved the expression of GD2 in neuroblastoma cells (CHP-134) and provided different effects in combination with the anti-GD2 antibody naxitamab. In particular, Nanofenretinide significantly increased the cytotoxic effect of naxitamab while Nanospermidine inhibited cell motility at extents proportional to naxitamab concentration. In neuroblastoma cells characterized by a low and heterogeneous basal expression of GD2, such as SH-SY5Y, which may represent the cell heterogeneity in tumors after chemotherapy, both Nanofenretinide and Nanospermidine increased GD2 expression in approximately 50% of cells, thus shifting the tumor population towards improved sensitivity to anti-GD2 antibodies.

Indoles constitute a large family of heterocyclic compounds widely occurring in nature which are present in a number of bioactive natural and synthetic compounds, including anticancer agents or atypical opioid agonists. As a result, exponential increases in the development of novel methods for the synthesis of indole-containing compounds have been reported in the literature. A series of indole-aryl amide derivatives 1–7 containing tryptamine or an indolylacetic acid nucleus were designed, synthesized, and evaluated as opioid ligands. These new indole derivatives showed negligible to very low affinity for μ- and δ-opioid receptor (OR). On the other hand, compounds 2, 5 and 7 showed Ki values in the low μM range for κ-OR. Since indoles are well known for their anticancer potential, their effect against a panel of tumor cell lines was tested. The target compounds were evaluated for their in vitro cytotoxicity in HT29, HeLa, IGROV-1, MCF7, PC-3, and Jurkat J6 cells. Some of the synthesized compounds showed good activity against the selected tumor cell lines, with the exception of IGROV1. In particular, compound 5 showed a noteworthy selectivity towards HT29 cells, a malignant colonic cell line, without affecting healthy human intestinal cells. Further studies revealed that 5 caused the cell cycle arrest in the G1 phase and promoted apoptosis in HT29 cells.

A series of naphthoquinones, namely, 1,4-naphthoquinone, menadione, plumbagin, juglone, naphthazarin, and lawsone, were reacted with N-acetyl-L-cysteine, and except for lawsone, which did not react, the related adducts were obtained. After the tuning of the solvent and reaction conditions, the reaction products were isolated as almost pure from the complex reaction mixture via simple filtration and were fully characterized. Therefore, the aim of this work was to evaluate whether the antitumor activity of new compounds of 1,4-naphthoquinone derivatives leads to an increase in ROS in tumor cell lines of cervical carcinoma (HeLa), neuroblastoma (SH-SY5Y), and osteosarcoma (SaOS2, U2OS) and in normal dermal fibroblast (HDFa). The MTT assay was used to assay cell viability, the DCF-DA fluorescent probe to evaluate ROS induction, and cell-cycle analysis to measure the antiproliferative effect. Compounds 8, 9, and 12 showed a certain degree of cytotoxicity towards all the malignant cell lines tested, while compound 11 showed biological activity at higher IC50 values. Compounds 8 and 11 induced increases in ROS generation after 1 h of exposure, while after 48 h of treatment, only 8 induced an increase in ROS formation in HeLa cells. Cell-cycle analysis showed that compound 8 caused an increase in the number of G0/G1-phase cells in the HeLa experiment, while for the U2OS and SH-SY5Y cell lines, it led to an accumulation of S-phase cells. Therefore, these novel 1,4-naphthoquinone derivatives may be useful as antitumoral agents in the treatment of different cancers.

Primary soft-tissue lymphoma (PSTL) is a rare extranodal non-Hodgkin lymphoma, characterized by a mass growing within soft-tissue, which is connective tissue, adipose tissue, and skeletal muscle. Here, we describe a case of biphenotypic lymphoblastic lymphoma arising from soft tissue of the popliteal fossa in an 11-year-old boy. A pediatric review about PSTL revealed that anaplastic large cell lymphoma is the most common histological type and a biphenotypic lymphoblastic lymphoma has not yet been reported in childhood. Lymphoma should always be considered in patients presenting with a soft-tissue mass, and a comprehensive immunohistochemical evaluation, including B-cell, T-cell, and myeloid markers, is needed to make a correct diagnosis and establish the most suitable treatment.

Osteosarcoma (OS) is a malignant disease characterized by poor prognosis due to a high incidence of metastasis and chemoresistance. Recently, Licochalcone A (Lic-A) has been reported as a promising agent against OS. Starting from chalcones selected from a wide in-house library, a new series was designed and synthetized. The antitumor activity of the compounds was tested on the MG63 OS cell line through the innovative Quantitative Phase Imaging technique and MTT assay. To further investigate the biological profile of active derivatives, cell cycle progression and apoptosis induction were evaluated. An earlier and more consistent arrest in the G2-M phase with respect to Lic-A was observed. Moreover, apoptosis was assessed by Annexin V staining as well as by the detection of typical morphological features of apoptotic cells. Among the selected compounds, 1e, 1q, and 1r proved to be the most promising antitumor molecules. This study pointed out that an integrated methodological approach may constitute a valuable platform for the rapid screening of large series of compounds.

A new strategy to cause cell death in tumors might be the increase of intracellular polyamines at concentrations above their physiological values to trigger the production of oxidation metabolites at levels exceeding cell tolerance. To test this hypothesis, we prepared nanospermidine as a carrier for spermidine penetration into the cells, able to escape the polyamine transport system that strictly regulates intracellular polyamine levels. Nanospermidine was prepared by spermidine encapsulation in nanomicelles and was characterized by size, zeta potential, loading, dimensional stability to dilution, and stability to spermidine leakage. Antitumor activity, ROS production, and cell penetration ability were evaluated in vitro in two neuroblastoma cell lines (NLF and BR6). Nanospermidine was tested as a single agent and in combination with nanofenretinide. Free spermidine was also tested as a comparison. The results indicated that the nanomicelles successfully transported spermidine into the cells inducing cell death in a concentration range (150–200 μM) tenfold lower than that required to provide similar cytotoxicity with free spermidine (1500–2000 μM). Nanofenretinide provided a cytostatic effect in combination with the lowest nanospermidine concentrations evaluated and slightly improved nanospermidine cytotoxicity at the highest concentrations. These data suggest that nanospermidine has the potential to become a new approach in cancer treatment. At the cellular level, in fact, it exploits polyamine catabolism by means of biocompatible doses of spermidine and, in vivo settings, it can exploit the selective accumulation of nanomedicines at the tumor site. Nanofenretinide combination further improves its efficacy. Furthermore, the proven ability of spermidine to activate macrophages and lymphocytes suggests that nanospermidine could inhibit immunosuppression in the tumor environment.

The onion is one of the most widespread bulb vegetables worldwide. Onion cultivation is common in Sicily, as is the use of local genotypes. Cultivation practices are of particular interest in optimizing yield, quality, and profits. The aim of this study was to assess the agronomic response of a Sicilian landrace (Bianca Calda di Comiso, coded L1) and a commercial variety (Bianca di Maggio, coded V1) to different planting dates and N fertilization rates. An economic appraisal was also performed. The two genotypes were assessed using an experimental split-split-plot design with four levels of nitrogen rates (0, 80, 160, and 220 kg N ha−1) and two different planting dates (8 October 2005 to 9 October 2006 for the early planting date, and 27 December 2005 to 30 December 2006 for the traditional planting date). The marketable yield and production parameters were significantly influenced by the nitrogen dose: higher doses led to a higher total yield, with yield peaks above 60 t ha−1 and the marketable yield ranging from 23% to 54%. Simultaneously, decreases in the firmness (from 7% to 19%) and scale content (from 1% to 3%) were also reported. The L1 landrace showed a higher production than the V1 variety. The crop year did not significantly affect the results, and the traditional planting date appeared to be the most suitable choice in obtaining the best agronomic response. Economic analysis showed that the L1 landrace, with high-N application treatments, produced greater net benefits and marginal rates of return. Thus, the L1 landrace exposed to the highest dosages of nitrogen (160 or 220 kg ha−1) and transplanted during the traditional planting period is the best choice from agronomic and economic points of view.

Valorization of wild plants to obtain botanical ingredients could be a strategy for sustainable production of cosmetics. This study aimed to select the rosehip extract containing the greatest amounts of bioactive compounds and to encapsulate it in vesicular systems capable of protecting their own antioxidant activity. Chemical analysis of Rosa canina L. extracts was performed by LC-DAD-MS/MS and 1H-NMR and vitamins, phenolic compounds, sugars, and organic acids were detected as the main compounds of the extracts. Liposomes, prepared by the film hydration method, together with hyalurosomes and ethosomes, obtained by the ethanol injection method, were characterized in terms of vesicle size, polydispersity index, entrapment efficiency, zeta potential, in vitro release and biocompatibility on WS1 fibroblasts. Among all types of vesicular systems, ethosomes proved to be the most promising nanocarriers showing nanometric size (196 ± 1 nm), narrow polydispersity (0.20 ± 0.02), good entrapment efficiency (92.30 ± 0.02%), and negative zeta potential (−37.36 ± 0.55 mV). Moreover, ethosomes showed good stability over time, a slow release of polyphenols compared with free extract, and they were not cytotoxic. In conclusion, ethosomes could be innovative carriers for the encapsulation of rosehip extract.

A series of regioisomers of the hydroxystearic acid (HSA) was prepared, and the effect of the position of the hydroxyl group along the chain on a panel of human cancer cell lines was investigated. Among the various regioisomers, those carrying the hydroxyl at positions 5, 7, and 9 had growth inhibitor activity against various human tumor cell lines, including CaCo-2, HT29, HeLa, MCF7, PC3, and NLF cells. 10-HSA and 11-HSA showed a very weak effect. 8-HSA did not show inhibitory activity in all cell lines. The biological role of 7-HSA and 9-HSA is widely recognized, while little is known about the effects of 5-HSA. Therefore, the biological effects of 5-HSA in HeLa, HT29, MCF7, and NLF cell lines were investigated using the Livecyte’s ptychography technology, which allows correlating changes in proliferation, motility, and morphology as a function of treatment at the same time. 5-HSA not only reduces cell proliferation but also induces changes in cell displacement, directionality, and speed. It is important to characterize the biological effects of 5-HSA, this molecule being an important component of fatty acyl esters of hydroxy fatty acids (FAHFA), a class of endogenous mammalian lipids with noticeable anti-diabetic and anti-inflammatory effects.

Salvia sclarea L. is an important industrial crop, valued for its herbal-aromatic properties and high quality essential oils, that is used in food, pharmaceuticals and cosmetics. In this study, carried out from 2009 to 2010, the morphological and production characteristics and essential oil content and composition of three Sicilian populations were studied. In particular, the composition of essential oils extracted from primary and secondary inflorescences using steam distillation was assessed. Morphological, production and qualitative data from the three populations were subjected to analysis of variance and cluster analysis. Regarding the quality of the oils, only the most prevalent compounds were taken into consideration in this study. The three populations were linalyl acetate/linalool chemotypes. Highly significant variations were found for the effective local population and inflorescence type in the composition of the essential oil principal components. In particular, the primary inflorescences were found to be accumulation sites favoured by monoterpenes, and secondary inflorescences were favoured by sesquiterpenes and sclareol. Populations “S. Stefano Quisquina” and “Alcara Li Fusi” performed best on a morphological and production level, whereas populations “Prizzi”and “Alcara Li Fusi” performed best in terms of quality. Population “S. Stefano Quisquina” produced high levels of sclareol. Biotype selection from within the populations should be based on both morphological, production and quality analyses.

Studies on vitamin/hormone D deficiency have received a vast amount of attention in recent years, particularly concerning recommendations, guidelines, and treatments. Moreover, vitamin D’s role as a hormone has been confirmed in various enzymatic, metabolic, physiological, and pathophysiological processes related to many organs and systems in the human body. This growing interest is mostly due to the evidence that modest-to-severe vitamin D deficiency is widely prevalent around the world. There is broad agreement that optimal vitamin D status is necessary for bones, muscles, and one’s general health, as well as for the efficacy of antiresorptive and anabolic bone-forming treatments. Food supplementation with vitamin D, or the use of vitamin D supplements, are current strategies to improve vitamin D levels and treat deficiency. This article reviews consolidated and emerging concepts about vitamin D/hormone D metabolism, food sources, deficiency, as well as the different vitamin D supplements available, and current recommendations on the proper use of these compounds.

The roots of two cultivars of Paeonia, namely Paeonia officinalis “Rubra Plena” and Paeonia “Pink Hawaiian Coral”, have been extracted with chloroform. The composition of the lipid fraction, analyzed by GC–MS technique, revealed the absence of paeonol and the presence of phenol, benzoic acid, fatty acid—and some sterol—derivatives. The chloroformic extracts have been tested on normal and several cancer cell lines but showed antiproliferative activity only on the ovarian carcinoma and the osteosarcoma. The biological activity of extracts was investigated mainly by confocal microscopy, flow cytometry and quantum phase imaging. The results indicated that the root extracts induced a hyperpolarization of mitochondria and an increase in reactive oxygen species levels, without inducing cell death. These effects are associated to an increased doubling time and a retarded confluence.

Remote sensing of the atmospheric composition from current and future satellites, such as the Sentinel missions of the Copernicus programme, yields an unprecedented amount of data to monitor air quality, ozone, UV radiation and other climate variables. Hence, full exploitation of the growing wealth of information delivered by spaceborne observing systems requires addressing the technological challenges for developing new strategies and tools that are capable to deal with these huge data volumes. The H2020 AURORA (Advanced Ultraviolet Radiation and Ozone Retrieval for Applications) project investigated a novel approach for synergistic use of ozone profile measurements acquired at different frequencies (ultraviolet, visible, thermal infrared) by sensors onboard Geostationary Equatorial Orbit (GEO) and Low Earth Orbit (LEO) satellites in the framework of the Copernicus Sentinel-4 and Sentinel-5 missions. This paper outlines the main features of the technological infrastructure, designed and developed to support the AURORA data processing chain as a distributed data processing and describes in detail the key components of the infrastructure and the software prototype. The latter demonstrates the technical feasibility of the automatic execution of the full processing chain with simulated data. The Data Processing Chain (DPC) presented in this work thus replicates a processing system that, starting from the operational satellite retrievals, carries out their fusion and results in the assimilation of the fused products. These consist in ozone vertical profiles from which further modules of the chain deliver tropospheric ozone and UV radiation at the Earth’s surface. The conclusions highlight the relevance of this novel approach to the synergistic use of operational satellite data and underline that the infrastructure uses general-purpose technologies and is open for applications in different contexts.

The common reed (Phragmites australis) has long been used in wetlands of the French Atlantic coast as fodder and bedding or roof thatching, among other uses. This article explores the practical and economic aspects of utilizing common reed for housing suckler cows compared to straw. Based on a study conducted over two years on a research farm of the French National Research Institute for Agriculture, Food and the Environment (INRAE), located in the marshes of Rochefort-sur-Mer, we show that reed is a good alternative to cereal straw and its cost is quite competitive compared to straw; the closer the reed bed is to the farm, the more competitive it is. By mobilizing the concept of restoration of natural capital, we lay the foundations for a debate on a possible revival of this ancient practice, with the idea that ecological restoration of reed beds can benefit biodiversity and the economy of wetlands farms.

The focus of this work was to prepare Spanish Broom, flax, and hemp dressings impregnated with glycyrrhetinic acid (GA) liposomes or hyalurosomes to promote the healing process and protect the skin wounds. Vesicles were prepared by the film hydration method and characterized in terms of size, particle size distribution, ζ potential, encapsulation efficiency, in vitro release, and biocompatibility on 3T3 fibroblasts. Loaded liposomes and hyalurosomes showed nanometric size (355 ± 19 nm and 424 ± 32 nm, respectively), good size distribution (lower than 0.3), and appropriate encapsulation efficiency (58.62 ± 3.25% and 59.22 ± 8.18%, respectively). Hyalurosomes showed good stability during the storage period, which can be correlated to the negative ζ potential, and allowed a fast and complete release of GA. Preliminary biological studies revealed that both kinds of loaded vesicles were not cytotoxic and that hyalurosomes could exert a slight stimulating effect on fibroblast proliferation. Finally, in vitro release studies from the different dressings impregnated with the loaded vesicles demonstrated that a high amount of GA could be reached at the wound site after 60 min from application. In conclusion, the results suggested that the developed dressings, especially those impregnated with hyalurosomes, can be efficiently used to promote the healing process.

Nine compounds bearing pyridinyl (or piperidinyl, benzimidazolyl, benzotriazolyl) groups bound to an azelayl moiety through an amide bond were synthesized. The structural analogy with some histone deacetylase inhibitors inspired their syntheses, seeking new selective histone deacetylase inhibitors (HDACi). The azelayl moiety recalls part of 9-hydroxystearic acid, a cellular lipid showing antiproliferative activity toward cancer cells with HDAC as a molecular target. Azelayl derivatives bound to a benzothiazolyl moiety further proved to be active as HDACi. The novel compounds were tested on a panel of both normal and tumor cell lines. Non-specific induction of cytotoxicity was observed in the normal cell line, while three of them induced a biological effect only on the osteosarcoma (U2OS) cell line. One of them induced a change in nuclear shape and size. Cell-cycle alterations are associated with post-transcriptional modification of both H2/H3 and H4 histones. In line with recent studies, revealing unexpected HDAC7 function in osteoclasts, molecular docking studies on the active molecules predicted their proneness to interact with HDAC7. By reducing side effects associated with the action of the first-generation inhibitors, the herein reported compounds, thus, sound promising as selective HDACi.

We report a case of paroxysmal nocturnal hemoglobinuria (PNH) in a 14 year-old girl presenting a cerebral arterial thrombosis. The initial diagnosis was carential anemia due to menarche following identification of slight macrocytic anemia, leucopenia and mild thrombocytopenia at routine blood analysis. The child was eventually referred to a children’s hospital after the onset of progressive fatigue, anorexia and paleness. Severe anemia (hemoglobin 6 g/dL) with negative Coombs test, mild leucopenia (white blood cells 4.9×109/L) and thrombocytopenia (platelets 97×109/L) and high values of lactate dehydrogenase (2855 U/L) were identified; a packed red cells transfusion was administered. Her condition worsened and she subsequently presented complete right hemiplegia, aphasia and coma; magnetic resonance imaging revealed a massive ischemic lesion. A diagnosis of PNH was eventually made following high sensitivity flow cytometry, which identified a PNH clone (CD66b negative equal to 93.7% of granulocytes). Fast recovery from neurologic and hematological problems occurred in response to anticoagulant therapy and intravenous therapy with eculizumab. We are convinced that PNH should be included in the differential diagnosis of children presenting with cytopenia.

With the launch of the Sentinel-5 Precursor (S-5P, lifted-off on 13 October 2017), Sentinel-4 (S-4) and Sentinel-5 (S-5)(from 2021 and 2023 onwards, respectively) operational missions of the ESA/EU Copernicus program, a massive amount of atmospheric composition data with unprecedented quality will become available from geostationary (GEO) and low Earth orbit (LEO) observations. Enhanced observational capabilities are expected to foster deeper insight than ever before on key issues relevant for air quality, stratospheric ozone, solar radiation, and climate. A major potential strength of the Sentinel observations lies in the exploitation of complementary information that originates from simultaneous and independent satellite measurements of the same air mass. The core purpose of the AURORA (Advanced Ultraviolet Radiation and Ozone Retrieval for Applications) project is to investigate this exploitation from a novel approach for merging data acquired in different spectral regions from on board the GEO and LEO platforms. A data processing chain is implemented and tested on synthetic observations. A new data algorithm combines the ultraviolet, visible and thermal infrared ozone products into S-4 and S-5(P) fused profiles. These fused products are then ingested into state-of-the-art data assimilation systems to obtain a unique ozone profile in analyses and forecasts mode. A comparative evaluation and validation of fused products assimilation versus the assimilation of the operational products will seek to demonstrate the improvements achieved by the proposed approach. This contribution provides a first general overview of the project, and discusses both the challenges of developing a technological infrastructure for implementing the AURORA concept, and the potential for applications of AURORA derived products, such as tropospheric ozone and UV surface radiation, in sectors such as air quality monitoring and health.

Diamond Blackfan anemia typically presents in infants and is often associated with many kinds of malformations. Severity of anemia often needs transfusional support in the first months of life. We describe here a patient with Diamond Blackfan anemia related to a RPL5 mutation. The patient had no physical abnormalities and experienced a very late onset of transfusion dependency.

Evans Syndrome is a rare autoimmune disease consisting of hemolytic anemia, thrombocytopenia and/or neutropenia. It may be associated with other autoimmune or lymphoproliferative diseases. Its course can be extremely serious and, rarely, even life-threatening; thus it represents a excellent treatment challenge for the pediatric hematologist. First line treatment consists of steroids and/or immunoglobulin; further therapy with rituximab, vincristine, cyclophosphamide and other immunosuppressive drugs can be considered in unresponsive patients. We describe a baby with refractory Evans Syndrome that was cured by prolonged administration of mycophenolate mofetil and remained disease-free for 4 years after the discontinuation of treatment.

Rationale: Therapy response evaluation by 18F-fluorodeoxyglucose PET/CT (FDG PET) has become a powerful tool for the discrimination of responders from non-responders in pediatric Hodgkin lymphoma (HL). Recently, volumetric analyses have been regarded as a valuable tool for disease prognostication and biological characterization in cancer. Given the multitude of methods available for volumetric analysis in HL, the AIEOP Hodgkin Lymphoma Study Group has designed a prospective analysis of the Italian cohort enrolled in the EuroNet-PHL-C2 trial. Methods: Primarily, the study aimed to compare the different segmentation techniques used for volumetric assessment in HL patients at baseline (PET1) and during therapy: early (PET2) and late assessment (PET3). Overall, 50 patients and 150 scans were investigated for the current analysis. A dedicated software was used to semi-automatically delineate contours of the lesions by using different threshold methods. More specifically, four methods were applied: (1) fixed 41% threshold of the maximum standardized uptake value (SUVmax) within the respective lymphoma site (V41%), (2) fixed absolute SUV threshold of 2.5 (V2.5); (3) SUVmax(lesion)/SUVmean liver >1.5 (Vliver); (4) adaptive method (AM). All parameters obtained from the different methods were analyzed with respect to response. Results: Among the different methods investigated, the strongest correlation was observed between AM and Vliver (rho > 0.9; p < 0.001 for SUVmean, MTV and TLG at all scan timing), along with V2.5 and AM or Vliver (rho 0.98, p < 0.001 for TLG at baseline; rho > 0.9; p < 0.001 for SUVmean, MTV and TLG at PET2 and PET3, respectively). To determine the best segmentation method, we applied logistic regression and correlated different results with Deauville scores at late evaluation. Logistic regression demonstrated that MTV (metabolic tumor volume) and TLG (total lesion glycolysis) computation according to V2.5 and Vliver significantly correlated to response to treatment (p = 0.01 and 0.04 for MTV and 0.03 and 0.04 for TLG, respectively). SUVmean also resulted in significant correlation as absolute value or variation. Conclusions: The best correlation for volumetric analysis was documented for AM and Vliver, followed by V2.5. The volumetric analyses obtained from V2.5 and Vliver significantly correlated to response to therapy, proving to be preferred thresholds in our pediatric HL cohort.

Background: The association between inflammatory bowel disease (IBD) and immune thrombocytopenia (ITP) is still uncertain. In this multicenter retrospective study, the coexistence of both diseases was investigated in children diagnosed from 1 January 2000 to 31 December 2019., Methods: Clinical characteristics of both IBD and ITP, onset of disorders, and patient's response to treatment were collected through a structured form sent to 55 Italian pediatric referring centers for hematological disorders., Result: Centers responded to the survey and reported the coexistence of IBD and ITP in 14 children. The first diagnosis was ITP in 57.1% and IBD in 35.7% of patients: it was simultaneous in 7.1%. IBD was classified as ulcerative colitis (57.1%), Crohn disease (35.7%), and unclassified (7.1%). No therapy for IBD other than steroids had any effect on ITP course. Colectomy resulted in recovery from ITP in 1 of the 2 patients surgically treated. ITP was always mild but turned to be chronic in half of patients., Conclusions: In all patients, ITP was mild without any evident impact on IBD severity, but the incidence of chronic ITP seems to be higher than what is usually observed in the pediatric age group. Colectomy had unpredictable effects on ITP.