Activity of Colocasia esculenta (Taro) Corms against Gastric Adenocarcinoma Cells: Chemical Study and Molecular Characterization.

Colocasia esculenta (L.) Schott is a tuberous plant, also known as taro, employed as food worldwide for its renowned nutritional properties but also traditionally used in several countries for medical purposes. In this study, methanolic extracts were prepared from the corms and leaves of Colocasia, subsequently fractionated via molecular exclusion chromatography (RP-HPLC) and their anti-tumor activity assessed in an in vitro model of gastric adenocarcinoma (AGS cells). Vorm extract and isolated fractions II and III affected AGS cell vitality in a dose-dependent manner through the modulation of key proteins involved in cell proliferation, apoptosis, and cell cycle processes, such as caspase 3, cyclin A, cdk2, IkBα, and ERK. To identify bioactive molecules responsible for anti-tumoral activity fractions II and III were further purified via RP-HPLC and characterized via nuclear magnetic resonance (NMR) and electrospray mass spectrometry (ESI-MS) techniques. The procedure enabled the identification of ten compounds including lignans and neolignans, some isolated for the first time in taro, uncommon megastigmane derivatives, and a gallic acid derivative. However, none of the isolated constituents showed efficacy equivalent to that of the fractions and total extract. This suggests that the whole Colocasia phytocomplex has intriguing anti-tumor activity against gastric cancer.

A Green Bioactive By-Product Almond Skin Functional Extract for Developing Nutraceutical Formulations with Potential Antimetabolic Activity.

(1) Background: almond peels are rich in polyphenols such as catechin and epicatechin, which are important anti-free-radical agents, anti-inflammatory compounds, and capable of breaking down cholesterol plaques. This work aims to evaluate the biological and technological activity of a "green" dry aqueous extract from Sicilian almond peels, a waste product of the food industry, and to develop healthy nutraceuticals with natural ingredients. Eudraguard® Natural is a natural coating polymer chosen to develop atomized formulations that improve the technological properties of the extract. (2) Methods: the antioxidant and free radical scavenger activity of the extract was rated using different methods (DPPH assay, ABTS, ORAC, NO). The metalloproteinases of the extracts (MMP-2 and MMP-9), the enhanced inhibition of the final glycation products, and the effects of the compounds on cell viability were also tested. All pure materials and formulations were characterized using UV, HPLC, FTIR, DSC, and SEM methods. (3) Results: almond peel extract showed appreciable antioxidant and free radical activity with a stronger NO inhibition effect, strong activity on MMP-2, and good antiglycative effects. In light of this, a food supplement with added health value was formulated. Eudraguard® Natural acted as a swelling substrate by improving extract solubility and dissolution/release (4) Conclusions: almond peel extract has significant antioxidant activity and MMP/AGE inhibition effects, resulting in an optimal candidate to formulate safe microsystems with potential antimetabolic activity. Eudraguard® Natural is capable of obtaining spray-dried microsystems with an improvement in the extract's biological and technological characteristics. It also protects the dry extract from degradation and oxidation, prolonging the shelf life of the final product.

Additive Manufacturing Strategies for Personalized Drug Delivery Systems and Medical Devices: Fused Filament Fabrication and Semi Solid Extrusion.

Novel additive manufacturing (AM) techniques and particularly 3D printing (3DP) have achieved a decade of success in pharmaceutical and biomedical fields. Highly innovative personalized therapeutical solutions may be designed and manufactured through a layer-by-layer approach starting from a digital model realized according to the needs of a specific patient or a patient group. The combination of patient-tailored drug dose, dosage, or diagnostic form (shape and size) and drug release adjustment has the potential to ensure the optimal patient therapy. Among the different 3D printing techniques, extrusion-based technologies, such as fused filament fabrication (FFF) and semi solid extrusion (SSE), are the most investigated for their high versatility, precision, feasibility, and cheapness. This review provides an overview on different 3DP techniques to produce personalized drug delivery systems and medical devices, highlighting, for each method, the critical printing process parameters, the main starting materials, as well as advantages and limitations. Furthermore, the recent developments of fused filament fabrication and semi solid extrusion 3DP are discussed. In this regard, the current state of the art, based on a detailed literature survey of the different 3D products printed via extrusion-based techniques, envisioning future directions in the clinical applications and diffusion of such systems, is summarized.

Congenital Solitary Kidney from Birth to Adulthood.

PURPOSE: To evaluate the course of prenatally diagnosed and early-enrolled congenital solitary functioning kidney patients followed until adulthood and to identify risk factors for kidney injury. MATERIALS AND METHODS: Among all congenital solitary functioning kidney patients followed (1993-2018), we recalled 56 patients with prenatal diagnosis and congenital solitary functioning kidney confirmation at 1-3 months of life reaching at least 18 years of age. Serum uric acid, heavy smoking (≥25 cigarettes/day) and overweight/obesity were clustered as modifiable risk factors. Kidney injury was defined by estimated glomerular filtration rate <90 ml/minute/1.73 m2 and/or 24-hour ambulatory blood pressure monitoring confirmed hypertension and/or proteinuria. Modifiable risk factors and congenital anomalies of the kidney and urinary tract (CAKUT) of congenital solitary functioning kidney were evaluated as risk factors for kidney injury. RESULTS: The mean followup period was 21.1 years (range 18-33 years). Mild kidney injury was found in 15 out of 56 patients (26.8%). The mean age at proteinuria, reduced estimated glomerular filtration rate and hypertension onset was 19.7 years (1.2 SDS), 20.7 years (2.7 SDS), and 22 years (5.6 SDS), respectively. Patients with CAKUT of congenital solitary functioning kidney and with both CAKUT of congenital solitary functioning kidney and modifiable risk factors presented survival free from kidney injury of 0% at 22.2 and 24.2 years of age, respectively. Patients with modifiable risk factors presented 42.4% of survival at 30 years. Patients without CAKUT of congenital solitary functioning kidney nor modifiable risk factors presented 100% of survival at 30 years of age (p=0.002). The presence of CAKUT of congenital solitary functioning kidney was the only significant risk factor (HR 4.9; 95% CI 1.8-14.2; p=0.003). CONCLUSIONS: The outcomes of congenital solitary functioning kidney in early adulthood appear better than previously reported. Prompt diagnosis of congenital solitary functioning kidney, healthy lifestyle promotion and monitoring of serum uric acid may improve the prognosis of congenital solitary functioning kidney patients.

Development of Chitosan/Mannitol Microparticles as Delivery System for the Oral Administration of a Spirulina Bioactive Peptide Extract.

Spirulina platensis contains several compounds showing nutritional and therapeutic benefits. Recently, a series of peptides able to reduce the blood pressure level and to enhance the endothelial vasorelaxation was isolated from the hydrolyzed highly water-soluble Spirulina extract (HSE). However, HSE shows critical organoleptic characteristics also having poor intestinal permeability, limiting absorption when orally delivered. This research aims to overcome the critical issues through the encapsulation of HSE in Chitosan/Mannitol-(CM)-based microparticles by spray drying. The produced powders (CM-HSE) showed good process yield (≈70%) and encapsulation efficiency (≈100%) also having good derived flow properties as well as stability up to six months storage. The microparticles constituting the spray-dried powder resulted in an amorphous micrometric state (d50 ≈ 14 µm) able to retain dark colour and unpleasant smell of raw HSE. Moreover, the in vitro permeation study by Franz cell indicated that the engineered microparticles are able to enhance the permeation of HSE through an intestinal biomimetic barrier (551.13 µg/cm2 CM-HSE vs. 315.46 µg/cm2 HSE at 270 min).

Design and Development of Spray-Dried Microsystems to Improve Technological and Functional Properties of Bioactive Compounds from Hazelnut Shells.

An extract obtained from hazelnut shells by-products (HSE) has antioxidant and chemopreventive effects on human melanoma and cervical cancer cell lines, inducing apoptosis by caspase-3 activation. A clinical translation is limited by poor water solubility and low bioavailability. Dried plant extracts often show critical characteristics such as sticky/gummy appearance, unpleasant smell, and instability involving practical difficulties in processing for industrial use. A spray drying method has been applied to transform raw HSE in a microparticulate powder. The biopolymeric matrix was based on l-proline as loading carrier, hydroxyethylcellulose in combination with pectin as coating polymers; lecithin and ethanol were used as solubility enhancers. A Hot-Cold-Hot method was selected to prepare the liquid feed. The thus prepared powder showed good technological properties (solid-state, particle dimensions, morphology, and water dissolution rate), stability, and unchanged chemopreventive effects with respect to the unprocessed HSE.

Antibiotics for urethral catheterization in children undergoing cystography: retrospective evaluation of a single-center cohort of pediatric non-toilet-trained patients.

Antibiotics are often used to prevent post-catheterization urinary tract infections (UTIs) in patients undergoing cystography. However, there is no universally accepted protocol and the literature data are conflicting. We aimed to determine prevalence and risk factors of post-cystography UTIs in non-toilet-trained children. We retrospectively evaluated 216 non-toilet-trained children not assuming antibiotics when undergoing cystography. Only the patients with dilated vesico-ureteral reflux (VUR) assumed antibiotics just after the exam (within 15 min). One hundred eleven patients without vesico-ureteral reflux (VUR) and 29 patients with non-dilated VUR did not receive post-procedure antibiotics and did not develop UTIs. Out of the 76 patients who showed a dilated VUR and received post-procedure antibiotics, only 5 (6.6%) developed a UTI. The most significant factor associated with post-cystography UTIs was the presence of dilated VUR (p = 0.005) with the presence of bilateral VUR also being significant (p = 0.02).Conclusion: Patients without dilated VUR or bilateral VUR could not benefit from antibiotic prophylaxis for cystography. What is Known: • There is no universally accepted protocol about antibiotic administration in children undergoing cystography. • Literature data are conflicting. What is New: • Among 216 non-toilet-trained children undergoing cystography, 111 patients without vesico-ureteral reflux (VUR) and 29 patients with non-dilated VUR did not receive post-procedure antibiotics and did not develop UTIs. Out of the 76 patients who showed a dilated VUR and received post-procedure antibiotics, only 5 (6.6%) developed a UTI. • The most significant factor associated to post-cystography UTIs was the presence of dilated VUR (p = 0.005) with presence of bilateral VUR also being significant (p = 0.02).

Halimium halimifolium: From the Chemical and Functional Characterization to a Nutraceutical Ingredient Design.

Halimium halimifolium (Hh) is a shrub used in Algerian folk medicine to treat gastrointestinal pain. An UHPLC-PDA-ESI/MSn method was developed to identify the metabolic profile of the traditionally used infusion (Hh-A) from the aerial parts. The structures of flavanols were confirmed by NMR analysis after the isolation procedure from a hydrohalcolic extract (Hh-B) that also allowed for the identification of phenolic acids, an aryl butanol glucoside, and different derivatives of quercetin, myricetin, and kaempferol. Tiliroside isomers were the chemical markers of Hh-A and Hh-B (54.33 and 36.00 mg/g, respectively). Hh-A showed a significant scavenging activity both against the radicals 1,1-diphenyl-2-picrylhydrazyl and 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (EC50 = 10.49 µg/mL and TEAC value = 1.98 mM Trolox/mg infusion) and the lipopolysaccharide-induced reactive oxygen species release in A375 and HeLa cells. Moreover, the antihyperglycemic properties, by inhibiting the α-amylase and α-glucosidase enzymes (IC50 = 0.82 mg/mL and 25.01 µg/mL, respectively), were demonstrated. To upgrade the therapeutic effect, a microencapsulation process is proposed as a strategy to optimize stability, handling, and delivery of bioactive components, avoiding the degradation and loss of the biological efficacy after oral intake. Hh-loaded microparticles were designed using cellulose acetate phthalate as the enteric coating material and spray drying as a production process. The results showed a satisfactory process yield (67.9%), encapsulation efficiency (96.7%), and micrometric characteristics of microparticles (laser-scattering, fluorescent, and scanning electron microscopy). In vitro dissolution studies (USPII-pH change method) showed that Hh-loaded microparticles are able to prevent the release and degradation of the bioactive components in the gastric tract, releasing them into the intestinal environment.

A Water-Soluble Microencapsulated Milk Thistle Extract as Active Ingredient for Dermal Formulations.

The choice of formulation is often of crucial importance in order to obtain a pharmaceutical product for the administration of poorly soluble drugs. Recently, a new water-soluble microparticulate powder form (MTE-mp) for the oral administration of a high functionality/low solubility silymarin rich milk thistle extract (MTE) has been developed. Findings showed that extract-loaded microparticles by spray-drying were produced with high and reproducible yields and encapsulation efficiency. The in vitro dissolution and permeation rates of silymarin were dramatically improved with respect to the raw material, and also enhanced the silymarin anti-inflammatory abilities. Given these successful results, the new MTE-mp delivery system has been proposed as an active ingredient for dermal applications. The aim of this research was the design and development of two topical formulations, hydrogel and emulgel (O/W emulsion), containing the MTE-mp delivery system or MTE raw extract. All the formulations were compared to each other in terms of handling and incorporation amount of the active ingredient during the productive process. Moreover, the addition to the emulgel of lecithin (L) as enhancer of permeation was tested. The MTE-mp ingredient that resulted was stable and more-easily incorporated both in hydrogel and emulgel than raw MTE extract, obtaining the best permeation profile for MTE-mp from emulgel with the addition of L. The obtained results confirm that the MTE-mp system could be used as a stable, water-soluble, and easy-handling functional ingredient, giving the opportunity to develop new strategies for MTE delivery in health products.

Chestnut (Castanea sativa Miller.) Burs Extracts and Functional Compounds: UHPLC-UV-HRMS Profiling, Antioxidant Activity, and Inhibitory Effects on Phytopathogenic Fungi.

Chestnut (Castanea sativa Miller.) burs (CSB) represent a solid waste produced during the edible fruit harvesting. Their usual disposal in the field increases the environmental and economic impact of the agricultural process. HPLC-UV-HRMS profiling revealed that CSB organic and aqueous extracts (CSB-M, CSB-H, CSB-A) contain several hydrolyzable tannins, mainly ellagitannins, and glycoside flavonols. Ellagic acid (EA) and chestanin are predominant components (5⁻79 and 1⁻13 mg/g dry extract, respectively). NMR analysis confirmed the chemical structures of the major constituents from CSB-M. The extracts displayed a significant scavenging activity against DPPH (EC50 12.64⁻24.94 µg/mL) and ABTS⁺ radicals (TEAC value 2.71⁻3.52 mM Trolox/mg extract). They were effective in inhibiting the mycelial growth (EC50 6.04⁻15.51 mg/mL) and spore germination (EC50 2.22⁻11.17 mg/mL) of Alternaria alternata and Fusarium solani. At the highest concentration, CSB-M was also active against Botrytis cinerea both in mycelium and spore form (EC50 64.98 and 16.33 mg/mL). The EA contributed to the antifungal activity of extracts (EC50 on spore germination 13.33⁻112.64 µg/mL). Our results can support the upgrading of chestnut burs from agricultural wastes to a resource of natural fungicides for managing fruit and vegetable diseases.

Application of Spray Drying Particle Engineering to a High-Functionality/Low-Solubility Milk Thistle Extract: Powders Production and Characterization.

Many natural compounds having antioxidant and anti-inflammatory activity are a potential target for new therapies against chronic inflammatory syndromes. The oral administration of functional herbal supplements may become a prevention strategy or therapy adjuvant for susceptible patients. A case study is our milk thistle (Silybum marianum) extract rich in silymarin complex. A water-soluble microencapsulated powder system was developed by a spray drying technique to improve the poor silymarin bioactivity after oral administration. Sodium carboxymethylcellulose (NaCMC) was employed as coating/swelling polymer matrix and sodium lauryl sulfate (SLS) as the surfactant (1:1:0.05 w/w/w). A H2O/EtOH/acetone (50/15/35 v/v/v) solvent system was used as liquid feed. The microsystems were capable of improving the in vitro dissolution and permeation rates, suggesting an enhancement of bioactivity after oral administration. The microsystems protect the antioxidant activity of silymarin after harsh storage conditions period and do not affect the anti-inflammatory properties of the raw extract (efficient already at lower concentrations of 0.312 mg/mL) to reduce dendritic cells (DCs) inflammatory cytokine secretion after lipopolysaccharide administration. This approach allows managing particle size, surface properties and release of bioactive agents improving the bioactivity of a herbal supplement and is also possibly applicable to many other similar natural products.

Outcomes of a Cohort of Prenatally Diagnosed and Early Enrolled Patients with Congenital Solitary Functioning Kidney.

PURPOSE: We evaluated the clinical course of patients prenatally diagnosed and enrolled early with congenital solitary functioning kidney, and identified the risk factors for renal injury. MATERIALS AND METHODS: We retrospectively evaluated 322 patients with congenital solitary functioning kidney according to the inclusion criteria of 1) prenatal diagnosis of solitary kidney; 2) first evaluation at 1 to 3 months of life with confirmation of congenital solitary functioning kidney, and evaluation of possible associated congenital anomalies of the kidney and urinary tract by abdominal ultrasound, renal scintigraphy and cystography; and 3) absence of any condition potentially affecting renal function in the neonatal period as well as absence of renal injury at enrollment (1 to 3 months of life) confirmed by a normal estimated glomerular filtration rate, lack of proteinuria and hypertension. Followup of 306 patients was evaluated. RESULTS: Median followup was 7.2 years (range 1 to 23) and 1 or more signs of renal injury were found in 12 of 306 patients (3.9%). Considering the entire population the cumulative proportion of patients free from renal injury at 17 years old was 93.7%, vs 81.3% and 95.9% for subjects with and those without congenital anomalies of the kidney and urinary tract of congenital solitary functioning kidney (p <0.001), respectively. Of congenital anomalies of the kidney and urinary tract, congenital solitary functioning kidney resulted in significant risk factors for renal injury (HR 8.75, 95% CI 2.77-27.65). CONCLUSIONS: In an evaluation of a large cohort of patients enrolled early with congenital solitary functioning kidney with a prenatal diagnosis, excluding those with neonatal onset of renal damage, the prevalence of renal damage was 3.9%. Among congenital anomalies of the kidney and urinary tract, congenital solitary functioning kidney represented the major risk factor.

Hazelnut (Corylus avellana L.) Shells Extract: Phenolic Composition, Antioxidant Effect and Cytotoxic Activity on Human Cancer Cell Lines.

Hazelnut shells, a by-product of the kernel industry processing, are reported to contain high amount of polyphenols. However, studies on the chemical composition and potential effects on human health are lacking. A methanol hazelnut shells extract was prepared and dried. Our investigation allowed the isolation and characterization of different classes of phenolic compounds, including neolignans, and a diarylheptanoid, which contribute to a high total polyphenol content (193.8 ± 3.6 mg of gallic acid equivalents (GAE)/g of extract). Neolignans, lawsonicin and cedrusin, a cyclic diarylheptanoid, carpinontriol B, and two phenol derivatives, C-veratroylglycol, and ß-hydroxypropiovanillone, were the main components of the extract (0.71%-2.93%, w/w). The biological assays suggested that the extract could be useful as a functional ingredient in food technology and pharmaceutical industry showing an in vitro scavenging activity against the radical 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) (EC50 = 31.7 µg/mL with respect to α-tocopherol EC50 = 10.1 µg/mL), and an inhibitory effect on the growth of human cancer cell lines A375, SK-Mel-28 and HeLa (IC50 = 584, 459, and 526 µg/mL, respectively). The expression of cleaved forms of caspase-3 and poly(ADP-ribose) polymerase-1 (PARP-1) suggested that the extract induced apoptosis through caspase-3 activation in both human malignant melanoma (SK-Mel-28) and human cervical cancer (HeLa) cell lines. The cytotoxic activity relies on the presence of the neolignans (balanophonin), and phenol derivatives (gallic acid), showing a pro-apoptotic effect on the tested cell lines, and the neolignan, cedrusin, with a cytotoxic effect on A375 and HeLa cells.

B cells from nuclear factor kB essential modulator deficient patients fail to differentiate to antibody secreting cells in response to TLR9 ligand.

Hypohidrotic ectodermal dysplasia (HED) consists of disorders resulting from molecular alterations of ectodysplasin-A (EDA) pathway. Hypomorphic mutations in NF-kB essential modulator, downstream EDA, result in HED with immunodeficiency (HED-ID), characterized by susceptibility to encapsulated pyogenic bacteria infections. Increased susceptibility to pneumococcal infections and poor response to polysaccharide antigens are associated with defect in T-independent B-cell immunity. We investigated B-cell differentiation and immunoglobulin secretion induced by the TLR9 ligand CpG in two HED-ID and in a HED patient caused by EDA mutations (XLHED). In HED-ID, only few B cells differentiated into plasma cells upon TLR9 stimulation and memory B cells did not produce IgG and IgA, but small amounts of IgM. Unexpectedly, memory B cells from XLHED patient failed to produce normal IgA or IgG amount upon TLR9 stimulation. Our findings expand the knowledge about the pathogenesis of humoral alterations in HED patients and help explain the susceptibility to pneumococcal infections.

Clinical relevance of thyroid cell models in redox research.

BACKGROUND: Thyroid-derived cell models are commonly used to investigate the characteristics of thyroid cancers. It is noteworthy that each in vitro single cell model system imitates only a few characteristics of thyroid cancer depending on e.g. source of cells or oncogene used to transform the cells. METHODS: In the current work we utilized rat thyroid cancer cell models to determine their clinical relevance in redox gene studies by comparing in vitro expression data to thyroid Oncomine microarray database. To survey the cell lines we analyzed mRNA expression of genes that produce superoxide anion (nox family), genes that catalyze destruction of superoxide anion to hydrogen peroxide (sod family), and genes that remove hydrogen peroxide from cellular environment (catalase, gpx family and prdx family). RESULTS: Based on the current results, rat thyroid PC Cl3, PC PTC1, PC E1A, or FRLT5 cell models can be used to study NOX2, NOX4, SOD2, SOD3, CATALASE, GPX1, GPX2, GPX5, PRDX2, and PRDX3 gene expression and function. CONCLUSIONS: Redox gene expression in rat originated single cell model systems used to study human thyroid carcinogenesis corresponds only partly with human redox gene expression, which may be caused by differences in redox gene activation stimulus. The data suggest careful estimation of the data observed in rat thyroid in vitro models.

Gastrointestinal involvement in patients affected with 22q11.2 deletion syndrome.

OBJECTIVE. Enteropathy is a very common feature in patients with primary immunodeficiencies. In patients with Del22 gastrointestinal (GI) alterations, including feeding disorders and congenital abnormalities have been often reported, mostly in the first year of life. MATERIAL AND METHODS. Aim of this monocentric study is to better define the GI involvement in a cohort of 26 patients affected with Del22 syndrome. Anamnestic information was retrospectively collected for each patient. Weight and height parameters at the time of the screening were recorded. Plasma levels of hemoglobin, iron, ferritin, albumin, total protein, calcium, phosphorus, transaminase levels, antigliadin (AGA) IgA and IgG, and antitissue transglutaminase (anti-TGase) titers were measured. RESULTS. A GI involvement was identified in the 58% of patients. The prominent problems were abdominal pain, vomiting, gastroesophageal reflux and chronic constipation. Weight deficiency, short stature and failure to thrive were reported in 54, 42, and 30% of the patients, respectively. The evidence of sideropenic anemia, in keeping with hypoproteinemia, impaired acid steatocrit or cellobiose/mannitol test suggested an abnormal intestinal permeability. In this cohort, a high prevalence of AGA IgA and IgG positivity was observed. Celiac disease (CD) was suspected in three patients, and in one of them confirmed by histology. In this patient, a long-lasting gluten-free diet failed to restore the intestinal architecture. CONCLUSIONS. In conclusion, GI involvement is a very common feature in Del22 patients. A better characterization of GI involvement would be very useful to improve the management of these patients.

The medieval skincare routine according to the formulations of Madgistra Trotula and the Medical School of Salerno and its reflection on cosmetology of the third millennium.

BACKGROUND: Officinal plants, minerals, animal derivatives, and miscellaneous have always been used to treat and improve appearance despite the different aesthetic canons of a specific historical and cultural context. OBJECTIVE: The aim of this work was to make a critical comparison between medieval and modern dermocosmetics analyzing the works of Trotula de Ruggiero, a female doctor of the 11th century teaching and working inside the illustrious "Medical School of Salerno," who devoted particular attention to the promotion of female care, beauty, and well-being. METHODS: We applied the historical-critical method analyzing the Latin text and the nglish translation of the standardized corpus of the main Trotula medieval manuscript De Ornatu Mulierum with a multidisciplinary scientific approach ranging from botany to pharmaceutical chemistry and technology, pharmacology and pathology. RESULTS: We identified the medicinal plants, derivatives of animal origin and minerals used in the recipes of Trotula, highlighting their biological properties in the light of current scientific knowledge. A critical comparison between medieval and modern dermocosmetics is reported also taking into consideration the chemical, pharmaceutical, and technological literature. CONCLUSION: Beyond the obvious changes in the paradigms of cosmetology and the different beauty canons of Middle Age with respect to modern times, our results emphasize the attention of Trotula to female care, beauty and well-being as well as the extraordinary combination of tradition and modernity in her work.

Couroupita guianensis bark decoction: From Amazonian medicine to the UHPLC-HRMS chemical profile and its role in inflammation processes and re-epithelialization.

ETHNOPHARMACOLOGICAL RELEVANCE: In the Amazon rainforest, the shamans of the Mayantuyacu site use the healing virtues of decoctions and teas from different parts of the Couroupita guianensis Aubl. (Lecythidaceae) trees as remedies in Ashaninka medicine. However, composition of the remedy and the underlying mechanism remain unclear. AIM OF THE STUDY: This study was designed to compare the metabolite profile of Couroupita guianensis bark decoction produced by Amazonian shamans with that obtained under standardised laboratory conditions and to investigate biological properties of both decoction and isolated constituents in skin wound healing process and inflammation. MATERIALS AND METHODS: The chemical analyses were carried out by Ultra-High-Performance Liquid Chromatography coupled with UV and High-Resolution Mass Spectrometry detectors (UHPLC-UV-HRMS). 1D and 2D-NMR experiments were performed to identify the main decoction constituents. The decoction and pure compound effect on keratinocyte migration was determined by the in vitro wound healing model; the mechanism of action was elucidated by western blot analysis. RESULTS: UHPLC-UV-HRMS analysis revealed the occurrence of polyphenolic compounds as catechins, ellagitannins and, notably, of unusual sulphated derivatives of ellagic acid isolated for the first time from Couroupita guianensis bark. A new natural sulphated molecule [4-(2″-O-sulphate- ß-D-glucuronopyranosyl) ellagic acid] was identified as the potential active compound responsible for the efficacy of bark decoction stimulating wound healing in human HaCaT keratinocytes. The molecular mechanism involved the induction of pro-migratory pathways mediated by ERK and AKT phosphorylation and the increase of MMP2 expression in HaCaT cells. At the same time, the treatment inhibited inflammation interfering with NFkB activation. CONCLUSION: Beyond identifying a new bioactive compound, the overall results scientifically validate the traditional use of Couroupita guianensis bark decoction as an anti-inflammatory remedy. Moreover, the beneficial effects on keratinocytes suggest promising therapeutic applications in skin diseases.

Inulin-g-poly-D,L-lactide, a sustainable amphiphilic copolymer for nano-therapeutics.

Cancer therapies started to take a big advantage from new nanomedicines on the market. Since then, research tried to better understand how to maximize efficacy while maintaining a high safety profile. Polyethylene glycol (PEG), the gold standard for nanomedicines coating design, is a winning choice to ensure a long circulation and colloidal stability, while in some cases, patients could develop PEG-directed immunoglobulins after the first administration. This lead to a phenomenon called accelerated blood clearance (ABC effect), and it is correlated with clinical failure because of the premature removal of the nanosystem from the circulation by immune mechanism. Therefore, alternatives to PEG need to be found. Here, looking at the backbone structural analogy, the hydrophilicity, flexibility, and its GRAS status, the natural polysaccharide inulin (INU) was investigated as PEG alternative. In particular, the first family of Inulin-g-poly-D,L-lactide amphiphilic copolymers (INU-PLAs) was synthesized. The new materials were fully characterized from the physicochemical point of view (solubility, 1D and 2D NMR, FT-IR, UV-Vis, GPC, DSC) and showed interesting hybrid properties compared to precursors. Moreover, their ability in forming stable colloids and to serve as a carrier for doxorubicin were investigated and compared with the already well-known and well-characterized PEGylated counterpart, polyethylene glycol-b-poly-D,L-lactide (PEG-PLA). This preliminary investigation showed INU-PLA to be able to assemble in nanostructures less than 200 nm in size and capable of loading doxorubicin with an encapsulation efficiency in the same order of magnitude of PEG-PLA analogues.

Recapsoma®: A Novel Mixture Based on Bergamot, Ipomoea Batatas, Policosanol Extracts and Liposomal Berberine for the Treatment of Hypercholesterolemia.

Cardiovascular disease (CVD) is considered one of the major causes of mortality worldwide. Epidemiological studies have shown that regular consumption of phenols is inversely associated with cardiovascular disease, and the use of nutraceuticals and functional foods can provide protective, preventive, and possibly curative effects in CVD. A novel mixture of different natural substances named Recapsoma® (bergamot, liposomal berberine, Ipomoea batatas, oleuropein, polycosanols, and vitamin E) has been produced, and its anti-dyslipidaemic efficacy has been tested, specifically studying the in vitro effects on the mechanisms of action underlying cholesterol synthesis, triglycerides, and LDL-cholesterol oxidation. The work has demonstrated the ability of this herbal extract mixture to inhibit the action of PCSK, ACAT, PAP, and HMGR and to increase the LDL receptor (LDLR), underlying the synergistic effect of the mixture over the single components. Such results suggest that the Recapsoma® mixture could be used as a tool for controlling hypercholesterolemia, and an alternative to statins, especially for those patients with metabolic syndrome.