Annurca Apple Oleolite as Functional Ingredient for the Formulation of Cosmetics with Skin-Antiaging Activity.

The identification of natural remedies for the management of the skin aging process is an increasingly growing issue. In this context, ursolic acid (UA), a ubiquitous molecule, mainly contained in Annurca apple (AA) fruit, has demonstrated valuable cosmetic potential. To this end, in the current study, the AA oleolite (AAO, extract in sunflower oil containing 784.40 ± 7.579 µg/mL of UA) was evaluated to inhibit porcine elastase enzymatic reactions through a validated spectrophotometric method. AAO has shown a valuable capacity to contrast the elastase enzyme with a calculated IC50 of 212.76 mg/mL, in comparison to UA (IC50 of 135.24 µg/mL) pure molecules and quercetin (IC50 of 72.47 µg/mL) which are used as positive controls. In this context and in view of the valuable antioxidant potential of AAO, its topical formulation with 2.5% (w/w) AAO was tested in a placebo-controlled, double-blind, two-arm clinical study on 40 volunteers. Our results indicated that after 28 days of treatment, a significant reduction of the nasolabial fold (-7.2 vs. baseline T0, p < 0.001) and forehead wrinkles (-5.3 vs. baseline T0, p < 0.001) were registered in combination with a valuable improvement of the viscoelastic skin parameters, where skin pliability/firmness (R0) and gross elasticity (R2) were significantly ameliorated (-13% vs. baseline T0, p < 0.001 for R0 and +12% vs. baseline T0, p < 0.001 for R2). Finally, considering the positive correlation between skin elasticity and hydration, the skin moisture was evaluated through the estimation of Trans epidermal water loss (TEWL) and skin conductance.

Agri-Food Waste Recycling for Healthy Remedies: Biomedical Potential of Nutraceuticals from Unripe Tomatoes (Solanum lycopersicum L.).

Unripe tomatoes represent an agri-food waste resulting from industrial by-processing products of tomatoes, yielding products with a high content of bioactive compounds with potential nutraceutical properties. The food-matrix biological properties are attributed to the high steroidal glycoalkaloid (SGA) content. Among them, α-tomatine is the main SGA reported in unripe green tomatoes. This review provides an overview of the main chemical and pharmacological features of α-tomatine and green tomato extracts. The extraction processes and methods employed in SGA identification and the quantification are discussed. Special attention was given to the methods used in α-tomatine qualitative and quantitative analyses, including the extraction procedures and the clean-up methods applied in the analysis of Solanum lycopersicum L. extracts. Finally, the health-beneficial properties and the pharmacokinetics and toxicological aspects of SGAs and α-tomatine-containing extracts are considered in depth. In particular, the relevant results of the main in vivo and in vitro studies reporting the therapeutic properties and the mechanisms of action were described in detail.

Phytochemical investigation and antioxidant properties of unripe tomato cultivars (Solanum lycopersicum L.).

Unripe tomatoes are among the main waste produced during tomato cultivation and processing. In this study, unripe tomatoes from seven different Italian cultivars have been investigated to evaluate their nutraceutical potential. Phytochemical investigation allowed shedding light on the identification of seventy-five bioactive compounds. The highest amount of polyphenolic and glycoalkaloids along with the high level of antioxidant activities was found in the Datterini tomatoes variety. The peculiarity of this variety is the high chlorogenic acid content, being ten times higher compared to the other cultivars examined. Moreover, the total α-tomatine amount has been found substantially higher (34.699 ± 1.101 mg/g dry weight) with respect to the other tomato varieties analyzed. Furthermore, the cultivars metabolomic profiles were investigated with the PCA approach. Based on Datterini cultivar's metabolomic profile, its waste-recovery could represent a good option for further added value products in pharmaceutical and nutraceutical areas with a high α-tomatine content.

Natural Chalcones for the Management of Obesity Disease.

In the last decade, the incidence of obesity has increased dramatically worldwide, reaching a dangerous pandemic spread. This condition has serious public health implications as it significantly increases the risk of chronic diseases such as type 2 diabetes, fatty liver, hypertension, heart attack, and stroke. The treatment of obesity is therefore the greatest health challenge of our time. Conventional therapeutic treatment of obesity is based on the use of various synthetic molecules belonging to the class of appetite suppressants, lipase inhibitors, hormones, metabolic regulators, and inhibitors of intestinal peptide receptors. The long-term use of these molecules is generally limited by various side effects and tolerance. For this reason, the search for natural alternatives to treat obesity is a current research goal. This review therefore examined the anti-obesity potential of natural chalcones based on available evidence from in vitro and animal studies. In particular, the results of the main in vitro studies describing the principal molecular therapeutic targets and the mechanism of action of the different chalcones investigated were described. In addition, the results of the most relevant animal studies were reported. Undoubtedly, future clinical studies are urgently needed to confirm and validate the potential of natural chalcones in the clinical prophylaxis of obesity.

A 52-week multicenter retrospective real-world study on effectiveness and safety of dupilumab in children with atopic dermatitis aged from 6 to 11 years.

Background: Dupilumab has been shown to be a safe and effective drug for the treatment of atopic dermatitis (AD) in children from 6 months to 11 years in randomized clinical trials. Aim: The aim of this real-life study was to determine the effectiveness in disease control and safety of dupilumab at W52 in moderate-to-severe AD children aged 6-11 years.Methods: All data were collected from 36 Italian dermatological or paediatric referral centres. Dupilumab was administered at label dosage with an induction dose of 300 mg on day 1 (D1), followed by 300 mg on D15 and 300 mg every 4 weeks (Q4W). Treatment effect was determined as overall disease severity, using EASI, P-NRS, S-NRS and c-DLQI at baseline, W16, W24, and W52. Ninety-six AD children diagnosed with moderate-to-severe AD and treated with dupilumab were enrolled.Results: Ninety-one (94.8%) patients completed the 52-week treatment period and were included in the study. A significant improvement in EASI score, P-NRS, S-NRS and c-DLQI was observed from baseline to weeks 16, 24 and 52.Conclusions: Our real-life data seem to confirm dupilumab effectiveness and safety in paediatric patients. Moreover, our experience highlighted that patients achieving clinical improvement at W16 preserved this condition over time.

Efficacy of a Multicomponent Nutraceutical Formulation for the Prevention and Treatment of Urinary Tract Stones.

Urolithiasis is a complex and multifactorial disease characterized by the formation of calculi at the urinary tract level. Conventional therapeutic prophylaxis relies on the use of Ca-blockers, alkalis, diuretics, and anti-edema agents, but their prolonged utilization is often limited by several side effects. In this scenario, the aim of the present work was the design of an innovative multi-component nutraceutical formulation (NF) for the management of urinary stones consisting of a synergistic combination of natural aqueous extracts of Oreganum vulgare L. (1% of saponin), Urtica dioica (0.8% of ß-sitosterol), Phyllanthus niruri (15% of tannins w/w), and Ceterach officinarum in association with bromelain, K, and Mg citrate. To assess the potential of NF also in the treatment of uric acid (UA) stones, the effects on the expression of the cellular UA transporters OAT1 and URAT1 were investigated in a renal tubular cell line. In addition, the myorelaxant effect of NF was investigated in a human pulmonary artery smooth muscle cell (HPASMC) model resulting in a decreased muscle contractility of -49.4% (p < 0.01) compared to the control. The treatment with NF also showed a valuable inhibition of in vitro calcium-oxalate crystal formation, both in prevention (-52.3% vs. control, p < 0.01) and treatment (-70.8% vs. control, p < 0.01) experiments. Finally, an ischemic reperfusion rat model was used to evaluate the NF anti-edema effects, resulting in a reduction in the edema-related vascular permeability (Normalized Gray Levels, NGL = 0.40 ± 0.09, p < 0.01, -67.1% vs. untreated rats). In conclusion, the present NF has shown to be a promising natural alternative for managing urinary tract stones.

Melanoma in children: A systematic review and individual patient meta-analysis.

The current evidence on paediatric melanoma is heterogeneous, especially regarding the prognosis of different histological subtypes. We sought to systematically review the evidence on paediatric melanoma, highlighting the major sources of heterogeneity and focusing on available data on single patients. A systematic search was performed from 1948 to 25 January 2021. Only studies reporting at least one case of cutaneous melanoma in patients aged ≤18 years were included. Unknown primary and uncertain malignant melanomas were excluded. Three couples of authors independently performed title/abstract screening and two different authors reviewed all the relevant full texts. The selected articles were manually cross-checked for overlapping data for qualitative synthesis. Subsequently data on single patients were extracted to perform a patient-level meta-analysis. PROSPERO registration number: CRD42021233248. The main outcomes were melanoma-specific survival (MSS) and progression-free survival (PFS) outcomes. Separate analyses were done of cases with complete information on histologic subtype, focusing on superficial spreading (SSM), nodular (NM) and spitzoid melanomas, as well as of those classified as de-novo (DNM) and acquired or congenital nevus-associated melanomas (NAM). The qualitative synthesis covered 266 studies; however, data on single patients were available from 213 studies including 1002 patients. Among histologic subtypes, NM had a lower MSS than both SSM and spitzoid melanoma, and a lower PFS than SSM. Spitzoid melanoma had a significantly higher progression risk than SSM and trended toward lower mortality. Focusing on nevus-associated status, DNM demonstrated better MSS after progression than congenital NAM, and no differences were highlighted in PFS. Our findings describe the existence of different biological patterns in paediatric melanoma. Specifically, spitzoid melanomas demonstrated intermediate behaviour between SSM and NM and showed a high risk of nodal progression but low mortality. This raises the question of whether spitzoid lesions are being over-diagnosed as melanoma in childhood.

Long-term efficacy and safety of secukinumab in real life: a 240 weeks multicenter study from Southern Italy.

BACKGROUND: Long-term real-life data on secukinumab use in psoriasis are limited. OBJECTIVES: Determine the long-term effectiveness of secukinumab in moderate-to-severe psoriasis in real-life. METHODS: Multicenter retrospective study analyzing data from adult patients treated with secukinumab for at least 192 weeks and up to 240 weeks in Southern Italy, between 2016 and 2021. Clinical data, including concurrent comorbidities and prior treatments were collected. Effectiveness was assessed by Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA), Dermatology Life Quality Index (DLQI) scores at the initiation of secukinumab and at weeks 4, 12, 24, 48, 96, 144, 192, and 240. RESULTS: Two hundred and seventy-five patients (174 males), mean age 50.80 ± 14.78 years, were included; 29.8% had an uncommon localization, 24.4% psoriatic arthritis, 71.6% comorbidities. PASI, BSA, and DLQI improved significantly from week 4 and continued to improve over time. Between weeks 24 and 240, PASI score was mild (≤10) in 97-100% of patients, 83-93% had mild affected BSA (BSA ≤ 3), and 62-90% reported no effect of psoriasis on their quality of life (DLQI 0-1). Only 2.6% of patients reported adverse events and no patient discontinued the treatment during the study period. CONCLUSIONS: Secukinumab effectiveness in the long-term treatment of psoriasis is confirmed in real-world.

Validation of an LC-MS/MS Method for the Determination of Abscisic Acid Concentration in a Real-World Setting.

One of the most relevant aspects in evaluating the impact of natural bioactive compounds on human health is the assessment of their bioavailability. In this regard, abscisic acid (ABA) has attracted particular interest as a plant-derived molecule mainly involved in the regulation of plant physiology. Remarkably, ABA was also found in mammals as an endogenous hormone involved in the upstream control of glucose homeostasis, as evidenced by its increase after glucose load. The present work focused on the development and validation of a method for the determination of ABA in biological samples through liquid-liquid extraction (LLE), followed by liquid mass spectrometry (LC-MS) of the extract. To test method suitability, this optimized and validated method was applied to a pilot study on eight healthy volunteers' serum levels to evaluate ABA concentration after consumption of a standardized test meal (STM) and the administration of an ABA-rich nutraceutical product. The results obtained could meet the demands of clinical laboratories to determine the response to a glucose-containing meal in terms of ABA concentration. Interestingly, the detection of this endogenous hormone in such a real-world setting could represent a useful tool to investigate the occurrence of impaired ABA release in dysglycemic individuals and to monitor its eventual improvement in response to chronic nutraceutical supplementation.