Search

Lignans, a class of secondary metabolites found in plants, along with their derivatives, exhibit diverse pharmacological activities, including antioxidant, antimicrobial, anti-inflammatory, and antiangiogenic ones. Angiogenesis, the formation of new blood vessels from pre-existing ones, is a crucial process for cancer growth and development. Several studies have elucidated the synergistic relationship between angiogenesis and inflammation in various inflammatory diseases, highlighting a correlation between inflammation and vascular endothelial growth factor (VEGF)-induced angiogenesis. Thus, the identification of novel molecules capable of modulating VEGF effects presents promising prospects for developing therapies aimed at stabilizing, reversing, or even arresting disease progression. Lignans often suffer from low aqueous solubility and, for their use, encapsulation in a delivery system is needed. In this research, a bioinspired benzoxantene has been encapsulated in solid lipid nanoparticles that have been characterized for their pharmacotechnical properties and their thermotropic behavior. The effects of these encapsulated nanoparticles on angiogenic parameters and inflammation in VEGF-induced angiogenesis were evaluated using human brain microvascular endothelial cells (HBMECs) as a human blood–brain barrier model.

Lignans and neolignans are dimeric natural products with an extraordinary variety of structures and biological properties. Diphenylbutadienes are a subclass of lignans rarely found in nature with cannabisin G being the most representative example. This lignan, found in Cannabis sativa seed, has shown anti-inflammatory and antioxidant activity among other biological properties. Different methodologies have been reported for the synthesis of cannabis G to be employed in new biological studies. We report herein a green and concise procedure based on the use of Trametes versicolor laccase for the synthesis of a new diphenylbutadiene. The developed procedure may be employed for the synthesis of cannabisin G and other analogues.

BackgroundFor patients with anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) and ovarian teratoma, “conservative” surgical approaches (complete or partial unilateral oophorectomy or bilateral partial oophorectomies) are associated with clinical improvement. “Aggressive” ovarian resections (complete bilateral oophorectomy or “blind” ovarian resections without pre-operative evidence of teratoma) are also reported, although the evidence supporting these approaches is unclear.ObjectiveTo compare the one-year functional outcomes of patients with NMDARE who underwent conservative vs. aggressive ovarian resections.MethodsPatients with NMDARE undergoing ovarian resection between January 1st, 2012 and December 31st, 2021 were retrospectively identified from three North American tertiary care centers. Primary outcome was a modified Rankin Scale score of 0–2 one year after ovarian resection. Fisher exact and Wilcoxon rank sum tests were used to compare demographic features, disease characteristics, and functional outcomes between the two surgical groups. A fixed-effects meta-analysis of studies reporting functional outcomes based on surgical approach was also performed.ResultsTwenty-three patients were included. Eight underwent aggressive surgical management. There was a non-significant trend toward an association between aggressive surgical management and younger age-at-onset, higher baseline disease severity, and longer delays to treatment. There was no difference between “aggressive” (3/8, 38%) and “conservative” (11/15, 73%) management groups in achieving the primary outcome (OR95% =

Colorectal cancer is one of the most diffused tumoral diseases. Since most medicaments employed for its treatment are debilitating, the use of naturally derived products, which can be effective against the mutated cells and, in addition, can reduce most inflammatory-related effects, could be extremely beneficial for the continued treatment of this disease. In this research, ethyl protocatechuate (PCAEE), a protocatechuic acid prodrug, was encapsulated in solid lipid nanoparticles (SLN) (prepared without and with Tween 80), which were characterized in terms of size, polydispersity index (PDI), zeta potential and thermotropic behavior. Encapsulation efficiency, release profile and interaction with a model of biomembrane were also assessed. The nanoparticles were tested in vitro on both healthy cells and on a model of tumoral cells. SLN prepared with Tween 80 was promising in terms of physicochemical properties (z-average of 190 nm, PDI 0.150 and zeta potential around −20 mV) and encapsulation efficiency (56%); they showed a desirable release profile, demonstrated an ability to penetrate and release the encapsulated PCAEE into a biomembrane model and were nontoxic on healthy cells. In addition, they caused a greater dose-dependent decrease in the viability of CaCo-2 cells than PCAEE alone. In conclusion, the formulation could be proposed for further studies to assess its suitability for the treatment of colorectal cancer.

Honokiol is a natural bisphenol neolignan present in the bark of Magnolia officinalis, whose extracts have been employed in oriental medicine to treat several disorders, showing a variety of biological properties, including antitumor activity, potentially related to radical scavenging. Six bisphenol neolignans with structural motifs related to the natural bioactive honokiol were synthesized. Their chain-breaking antioxidant activity was evaluated in the presence of peroxyl (ROO•) and hydroperoxyl (HOO•) radicals by both experimental and computational methods. Depending on the number and position of the hydroxyl and alkyl groups present on the molecules, these derivatives are more or less effective than the reference natural compound. The rate constant of the reaction with ROO• radicals for compound 7 is two orders of magnitude greater than that of honokiol. Moreover, for compounds displaying quinonic oxidized forms, we demonstrate that the addition of 1,4 cyclohexadiene, able to generate HOO• radicals, restores their antioxidant activity, because of the reducing capability of the HOO• radicals. The antioxidant activity of the oxidized compounds in combination with 1,4-cyclohexadiene is, in some cases, greater than that found for the starting compounds towards the peroxyl radicals. This synergy can be applied to maximize the performances of these new bisphenol neolignans.

Cancer progression is supported by the cross-talk between tumor cells and the surrounding stroma. In this context, senescent cells in the tumor microenvironment contribute to the development of a pro-inflammatory milieu and the acquisition of aggressive traits by cancer cells. Anticancer treatments induce cellular senescence (therapy-induced senescence, TIS) in both tumor and non-cancerous cells, contributing to many detrimental side effects of therapies. Thus, we focused on the effects of chemotherapy on the stromal compartment of prostate and ovarian cancer. We demonstrated that anticancer chemotherapeutics, regardless of their specific mechanism of action, promote a senescent phenotype in stromal fibroblasts, resulting in metabolic alterations and secretion of paracrine factors, sustaining the invasive and clonogenic potential of both prostate and ovarian cancer cells. The clearance of senescent stromal cells, through senolytic drug treatment, reverts the malignant phenotype of tumor cells. The clinical relevance of TIS was validated in ovarian and prostate cancer patients, highlighting increased accumulation of lipofuscin aggregates, a marker of the senescent phenotype, in the stromal compartment of tissues from chemotherapy-treated patients. These data provide new insights into the potential efficacy of combining traditional anticancer strategies with innovative senotherapy to potentiate anticancer treatments and overcome the adverse effects of chemotherapy.

Among grain pulses, lupins have recently gained considerable interest for a number of attractive nutritional attributes relating to their high protein and dietary fiber and negligible starch contents. The seeds of Lupinus albus (cv. Multitalia and Luxor, and the Modica ecotype); L. luteus (cv. Dukat, Mister, and Taper); and L. angustifolius (cv. Sonet) analyzed in this study were deposited within the germplasm collection of the Research Centre for Cereal and Industrial Crops of Acireale and were sowed in East Sicily in 2013/14. The collected seeds were analyzed for their multielemental micro- and macronutrient profiles, resulting in a wide variability between genotypes. Lupin seed flour samples were subjected to a defatting process using supercritical CO2, with oil yields dependent on the species and genotype. We determined the fatty acid profile and tocopherol content of the lupin oil samples, finding that the total saturated fatty acid quantities of different samples were very close, and the total tocopherol content was about 1500.00 µg/g FW. The proteomic analysis of the defatted lupin seed flours showed substantial equivalence between the cultivars of the same species of Lupinus albus and L. luteus. Moreover, the L. angustifolius proteome map showed the presence of additional spots in comparison to L. albus, corresponding to α-conglutins. Lupin, in addition to being a good source of mineral elements, also contributes vitamin E and, thanks to the very high content of gamma-tocopherols, demonstrates powerful antioxidant activity.

Neurodegenerative diseases affect millions of people worldwide and the presence of various physiological barriers limits the accessibility to the brain and reduces the efficacy of various therapies. Moreover, new carriers having targeting properties to specific brain regions and cells are needed in order to improve therapies for the brain disorder treatment. In this study, for the first time, Myelin nanoVesicles (hereafter defined MyVes) from brain-extracted myelin were produced. The MyVes have an average diameter of 100–150 ​nm, negative zeta potential, spheroidal morphology, and contain lipids and the key proteins of the myelin sheath. Furthermore, they exhibit good cytocompatibility. The MyVes were able to target the white matter and interact mainly with the microglia cells. The preliminary results here presented allow us to suppose the employment of MyVes as potential carrier to target the white matter and microglia in order to counteract white matter microglia-related diseases.

Skin is the first human barrier that is daily exposed to a broad spectrum of physical and chemical agents, which can increase reactive oxygen species (ROS) and lead to the formation of topical disorders. Antioxidant molecules, such as benzo[k,l]xanthene lignans (BXL), are ideal candidates to eliminate or minimize the effects of ROS. Herein, we aimed to formulate BXL-loaded solid lipid nanoparticles (SLN-BXL) to improve the bioavailability and interaction with the skin, and also to investigate the protective impact against intracellular ROS generation in HFF-1 in comparison with the drug-free situation. SLN-BXL were formulated using the PIT/ultrasonication method, and then were subjected to physicochemical characterizations, i.e., average size, zeta potential (ZP), polydispersity index (PDI), encapsulation efficiency (%EE), thermotropic behavior, and interaction with a biomembrane model. The results show a mean size around 200 nm, PDI of 0.2, and zeta potential of about −28 mV, with values almost unchanged over a period of three months, while the EE% is ≈70%. Moreover, SLN-BXL are able to deeply interact with the biomembrane model, and to achieve a double-action release in mildly hydrophobic matrices; the results of the in vitro experiments confirm that SLN-BXL are cell-safe and capable of attenuating the IL-2-induced high ROS levels. In conclusion, based on our findings, the formulation can be proposed as a candidate for a preventive remedy against skin disorders induced by increased levels of ROS.

Benzo[k,l]xanthene lignans are a group of rare natural products belonging to the class of polyphenols with promising biological activities and are studied as potential chemotherapeutic agents. The lipophilic character of a xanthene core makes these molecules difficult to be used in an aqueous medium, limiting their employment in studies for pharmaceutical applications. To overcome this problem, a drug-delivery system which is able to improve the stability and bioavailability of the compound can be used. In this study, a bioactive benzoxanthene lignan (BXL) has been included in SLN. Unloaded and BXL-loaded SLN have been prepared using the Phase Inversion Temperature method and characterized in terms of size, zeta potential, entrapment efficiency and stability. Differential scanning calorimetry was used to evaluate the thermotropic behavior and ability of SLN to act as carriers for BXL. A biomembrane model, represented by multilamellar vesicles, was used to simulate the interaction of the SLN with the cellular membrane. Unloaded and loaded SLN were incubated with the MLV, and their interactions were evaluated through variations in their calorimetric curves. The results obtained suggest that SLN could be used as a delivery system for BXL.

Currently, no commercially available drugs have the ability to reverse cachexia or counteract muscle wasting and the loss of lean mass. Here, we report the methodology used to develop Physiactisome—a conditioned medium released by heat shock protein 60 (Hsp60)—overexpressing C2C12 cell lines enriched with small and large extracellular vesicles. We also present evidence supporting its use in the treatment of cachexia. Briefly, we obtain a nanovesicle-based secretion by genetically modifying C2C12 cell lines with an Hsp60-overexpressing plasmid. The secretion is used to treat naïve C2C12 cell lines. Physiactisome activates the expression of PGC-1α isoform 1, which is directly involved in mitochondrial biogenesis and muscle atrophy suppression, in naïve C2C12 cell lines. Proteomic analyses show Hsp60 localisation inside isolated nanovesicles and the localisation of several apocrine and merocrine molecules, with potential benefits for severe forms of muscle atrophy. Considering that Physiactisome can be easily obtained following tissue biopsy and can be applied to autologous muscle stem cells, we propose a potential nanovesicle-based anti-cachexia drug that could mimic the beneficial effects of exercise. Thus, Physiactisome may improve patient survival and quality of life. Furthermore, the method used to add Hsp60 into nanovesicles can be used to deliver other drugs or active proteins to vesicles.

Inulin is considered a dietary fiber and represents a noteworthy ingredient for food biofortification due to its health effects and its neutral taste. The aim of the work was the evaluation of the quality of pasta produced using whole-meal flours of two ancient Sicilian landraces (Senatore Cappelli-CAP and Timilia—TIM) fortified with two types of inulin (long-chain topinambur inulin IT and low-chain chicory inulin IC), at two different levels of substitution (2 and 4%) to evaluate its possible effect on α-amylase inhibition. The color indices L* and a* were mainly influenced by cultivars, while IT improved the sensory attributes, mainly the elasticity sensation, and influenced less the other sensory attributes: adhesiveness, color, odor, taste, and Over Quality Score for both landraces. The cooking quality was linked mainly to the landrace used, due to the very different gluten matrix of CAP and TIM. IC and IT showed promising α-Amy inhibitory activity with comparable IC50 values of 0.45 ± 0.04 and 0.50 ± 0.06 mg/mL. The enrichment of spaghetti with inulin with an inhibitory effect on α-amylase determined the hypoglycemic properties of pasta, thus lowering the corresponding IC50 value.

The present work reports the first comprehensive proteomic profiling and qualitative comparison of metabolic and Chloroform-Methanol (CM)-like protein fractions extracted from mature kernels of two old Sicilian durum wheat landraces, Russello and Timilia Reste Bianche (Timilia RB), and Simeto, an improved durum wheat variety widespread in Italy and other Mediterranean countries and chosen as representative of the most widely commercial cultivars. The data are discussed in the related research article “Qualitative proteomic comparison of metabolic and CM-like protein fractions in old and modern wheat Italian genotypes by a shotgun approach” [1]. The results of this work could be used for in vitro investigations to understand the relationship between protein profiles of old and modern wheat genotypes and their potential benefits for human consumption. Keywords: Old and modern wheat genotypes, High resolution mass spectrometry, Proteome analysis, Proteins, Allergens, Food and nutrition

The agricultural processing industry usually generates a remarkable amount of by-products rich in bioactive compounds, which can be exploited for agri-food or nutraceutical applications. Pistachio’s hard shell is one of the major by-products from pistachio industrial processing. The aim of this work was the evaluation of pistachio shells as a potential source of natural antioxidants. We evaluated different extraction procedures by measuring total phenolic content, total flavonoid content and antioxidative activity (DPPH•, TEAC and ORAC). The microwave-assisted ethanol extract turned out to be the most promising and was fractionated by XAD-16 column chromatography, affording six fractions analyzed through HPLC/ESI-MS/MS and 1H-NMR to identify the main antioxidative constituents. Fractions Fr4–Fr6 demonstrated the highest antioxidant activity. Gallic acid and a monogalloylglusose isomer are the main phenolic constituents of Fr4. Both simple and complex phenolics, such as flavonoids and hydrolysable tannins, were identified in fractions Fr5 and Fr6; pentagalloylglucose and kaempferol, well-known for their antioxidant activity, are the most abundant constituents. The results highlighted that the proposed methodology can be an effective way to recover bioactive phenolic compounds from pistachio hard shell, making this by-product a promising source of compounds with potential applications in food and healthcare sectors.

Wheat represents one of the most important cereals for mankind. However, since wheat proteins are also the causative agent of several adverse reactions, during the last decades, consumers have shown an increasing interest in the old wheat genotypes, which are generally perceived as more “natural” and healthier than the modern ones. Comparison of nutritional value for modern and old wheat genotypes is still controversial, and to evaluate the real impact of these foods on human health comparative experiments involving old and modern genotypes are desirable. The nutritional quality of grain is correlated with its proteomic composition that depends on the interplay between the genetic characteristics of the plant and external factors related to the environment. We report here the label-free shotgun quantitative comparison of the metabolic protein fractions of two old Sicilian landraces (Russello and Timilia) and the modern variety Simeto, from the 2010–2011 and 2011–2012 growing seasons. The overall results show that Timilia presents the major differences with respect to the other two genotypes investigated. These differences may be related to different defense mechanisms and some other peculiar properties of these genotypes. On the other hand, our results confirm previous results leading to the conclusion that with respect to a nutritional value evaluation, there is a substantial equivalence between old and modern wheat genotypes. Data are available via ProteomeXchange with identifier .

The ethyl acetate extract of the commercial tannin Tan’Activ QS-SOL (from Schinopsis lorentzii wood), employed for the production of red wine, was subjected to chromatography on Sephadex LH-20, providing nine fractions (A-1–A-9), which were estimated for total phenols content (GAE), antioxidant activity (DPPH, ORAC), and hypoglycemic activity (α-glucosidase and α-amylase inhibition). All the fractions were analyzed by means of HPLC/ESI-MS/MS and 1H-NMR to identify the principal active constituents. Fractions A-1 and A-3 showed the highest antioxidant activity and gallic acid (1), pyrogallol (3), eriodictyol (6), catechin (12), and taxifolin (30) were identified as the major constituents. The highest α-glucosidase and α-amylase inhibitory activity was observed in fractions A-7–A-9 containing condensed (9′, 15, 18, 19, 23, and 27) hydrolysable tannins (13 and 32) as well as esters of quinic acid with different units of gallic acid (5, 11, 11′, 14, and 22). This last class of gallic acid esters are here reported for the first time as α-glucosidase and α-amylase inhibitors.

Durum wheat is widespread in the Mediterranean area, mainly in southern Italy, where traditional durum wheat breadmaking is consolidated. Bread is often prepared by adding a lot of salt to the dough. However, evidence suggests that excessive salt in a diet is a disease risk factor. The aim of this work is to study the effect of a natural low-sodium sea salt (Saltwell®) on bread-quality parameters and shelf-life. Bread samples were prepared using different levels of traditional sea salt and Saltwell®. The loaves were packaged in modified atmosphere conditions (MAPs) and monitored over 90 days of storage. No significant differences (p ≤ 0.05) were found in specific volumes and bread yield between the breads and over storage times, regardless of the type and quantity of salt used. Textural data, however, showed some significant differences (p ≤ 0.01) between the breads and storage times. 5-hydroxymethylfurfural (HMF) is considered, nowadays, as an emerging ubiquitous processing contaminant; bread with the lowest level of Saltwell® had the lowest HMF content, and during storage, a decrease content was highlighted. Sensory data showed that the loaves had a similar rating (p ≤ 0.05) and differed only in salt content before storage. This study has found that durum wheat bread can make a nutritional claim of being “low in sodium” and “very low in sodium”.

The aim of this work was to evaluate the effect of the addition of citrus fibers, from blood orange and lemon peels to produce a functional durum wheat bread. Breads fortified in fiber were packaged under a modified atmosphere (MAP) and stored at 25°C up to 120 days. No significant differences were observed with respect to the specific volume and weight, internal structure, pH and titratable acidity among the bread samples obtained using different types and percentages of fibers. Storage time, at 30 up to 90 days, affected significantly the bread firmness and caused significant differences in 5-hydroxymethylfurfural (HMF) levels in all bread samples. In fortified breads with citrus fibers the yeast and mold counts showed values of approximately 1 log10 cfu/g for the first 30 days and 3.5 log10 cfu/g at the end of storage. The results of the sensory evaluation highlight that loaves enriched with blood orange and lemon fibers showed a citrus flavor but had a similar overall evaluation respect to control bread produced without addition of citrus fiber. The results of this study showed that the addition up to 2% of blood orange and lemon fibers in wheat whole durum flour is a possible strategy to produce “high fibre” bread.

The use of plant water extracts to control weeds is gaining attention in environmentally-friendly agriculture, but the study of the effect that such extracts may exert on the yield of durum wheat is still unexplored. In 2014 and 2016, the herbicidal potential of several plant water extracts was field tested on durum wheat (cv Valbelice). In 2014, extracts obtained from Artemisia arborescens, Rhus coriaria, Lantana camara, Thymus vulgaris, and Euphorbia characias were used, whereas in 2016 only A. arborescens and R. coriaria were tested as “donor” plants. In both years, weed incidence was evaluated, together with the major yield parameters of wheat. None of the treatments (including chemicals) could eradicate weeds from the field. In 2014, dicots were in general prevailing in plots treated with extracts of E. characias, while monocots prevailed after treatments with L. camara and R. coriaria. In 2016, lower weed biomass and diversity level were found, and only Avena and Phalaris were detected at harvest time. Treatment with plant water extracts affected grain yields, but it seems likely that those effects are not due to the diverse incidence of weeds in treated and untreated plots, rather to some direct action exerted by allelopathic substances.

Drought stress is becoming more prevalent with global warming, and has been shown to have large effects on gluten proteins linked to wheat bread making quality. Likewise, low temperature stress can detrimentally affect proteins in wheat. This study was done to determine the differential abundance of high molecular weight (HMW) glutenin proteins in a drought and low temperature stressed high quality hard red spring wheat cultivar (PAN3478), against a control. The treatments were applied in the greenhouse at the soft dough stage. HMW glutenin proteins were extracted from the flour, and were separated by using two-dimensional gel electrophoresis. Protein spots that had p values lower than 0.05 and fold values equal to or greater than 1.2 were considered to be significantly differentially abundant. These proteins were further analyzed by using tandem mass spectrometry. There was a 1.3 to 1.8 fold change in 17 protein spots due to the cold treatment. The drought treatment caused a 1.3 to 3.8 fold change in 19 protein spots. These spots matched either HMW or low molecular weight (LMW) glutenin subunits. In the latter case, the C subunits of LMW glutenins were notably found to be up-regulated under both stress conditions. All the proteins that have been identified can directly influence dough characteristics. Data are available via ProteomeXchange with the identifier PXD017578.

The yeasts constitute a large group of microorganisms characterized by the ability to grow and survive in different and stressful conditions and then to colonize a wide range of environmental and human ecosystems. The competitive traits against other microorganisms have attracted increasing attention from scientists, who proposed their successful application as bioprotective agents in the agricultural, food and medical sectors. These antagonistic activities rely on the competition for nutrients, production and tolerance of high concentrations of ethanol, as well as the synthesis of a large class of antimicrobial compounds, known as killer toxins, which showed clearly a large spectrum of activity against food spoilage microorganisms, but also against plant, animal and human pathogens. This review describes the antimicrobial mechanisms involved in the antagonistic activity, their applications in the processed and unprocessed food sectors, as well as the future perspectives in the development of new bio-drugs, which may overcome the limitations connected to conventional antimicrobial and drug resistance.

Honokiol (2) is a natural bisphenol neolignan showing a variety of biological properties, including antitumor activity. Some studies pointed out 2 as a potential anticancer agent in view of its antiproliferative and pro-apoptotic activity towards tumor cells. As a further contribution to these studies, we report here the synthesis of a small library of bisphenol neolignans inspired by honokiol and the evaluation of their antiproliferative activity. The natural lead was hence subjected to simple chemical modifications to obtain the derivatives 3−9; further neolignans (12a-c, 13a-c, 14a-c, and 15a) were synthesized employing the Suzuki−Miyaura reaction, thus obtaining bisphenols with a substitution pattern different from honokiol. These compounds and the natural lead were subjected to antiproliferative assay towards HCT-116, HT-29, and PC3 tumor cell lines. Six of the neolignans show GI50 values lower than those of 2 towards all cell lines. Compounds 14a, 14c, and 15a are the most effective antiproliferative agents, with GI50 in the range of 3.6−19.1 µM, in some cases it is lower than those of the anticancer drug 5-fluorouracil. Flow cytometry experiments performed on these neolignans showed that the inhibition of proliferation is mainly due to an apoptotic process. These results indicate that the structural modification of honokiol may open the way to obtaining antitumor neolignans more potent than the natural lead.