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Background: Milk proteins (MPs) and their derivative whey proteins (WPs) are important components of human diet that might prevent bone loss. We aimed to investigate the effects of MP on the bones of postmenopausal women, along with the effects of WP on osteoblast cells. Methods: We conducted a feasibility controlled clinical study with 62 postmenopausal women who were asked to consume an MP-enriched ice cream. We also investigated the effect of WP on the ERK1/2 and AKT pathways, RUNX2, alkaline phosphatase, RANKL/OPG ratio, and COL1A of Saos-2. Results: After 12 weeks, we found a greater bone mineral density and bone alkaline phosphatase reduction in women who consumed the MP-enriched ice cream compared to the control group (p = 0.03 and p = 0.02, respectively). In Saos-2 cells, WP upregulated ERK1/2 and AKT pathways (p = 0.002 and p = 0.016), cell proliferation (p = 0.03), and osteoblast differentiation markers, along with downregulating RANKL/OPG (p < 0.001). Moreover, the inhibition of ERK1/2 by PD184253 reverted the effects on both the RUNX2 and ALP mRNA expression and cells proliferation (p = 0.028, p = 0.004, and p = 0.003, respectively) when treated with WP. Conclusions: WP upregulates cell proliferation, RUNX2, and alkaline phosphatase through the activation of the ERK1/2 pathways on Saos-2. These mechanisms probably contribute to preventing bone loss in postmenopausal women.

The World elderly population is expected to double before 2050. Unhealthy habits and unhealthy lifestyles are commonly associated with age-related diseases or their worsening. Modification in daily lifestyle and diet may help preventing age-related diseases onset and efficiently affecting their evolution, thus promoting the Healthy Aging process, concept recently coined to describe the disease-free aging process. This review highlights the role of nutrition science in promoting healthy aging. Since the Mediterranean Model demonstrated to be a useful style in supporting healthy aging, promotion of this correct lifestyle by health policies seems to be the best approach to achieve this target.

Osteoarthritis is a type of degenerative joint disease that results from the breakdown of joint cartilage and underlying bone. Due to their antioxidants and anti-inflammatory action, the phytochemical constituents of many vegetable varieties could represent a new frontier for the treatment of patients with Osteoarthritis and are still being explored. The aim of this pilot human study was to investigate the effects of pasta enriched with hemp seed flour on osteoarticular pain and bone formation markers in patients in post-arthroplasty rehabilitation. Another purpose was to evaluate the effect of hemp seed extract on bone metabolism, in vitro. A pilot, controlled, clinical study was conducted to verify the feasibility of pain symptom reduction in patients with Osteoarthritis undergoing arthroplasty surgery. We also investigated the effect of hemp seed extract on the Wnt/β-catenin and ERK1/2 pathways, alkaline phosphatase, RANKL, RUNX-2, osteocalcin, and COL1A on Saos-2. After 6 weeks, the consumption of hemp seed pasta led to greater pain relief compared to the regular pasta control group (−2.9 ± 1.3 cm vs. −1.3 ± 1.3 cm; p = 0.02). A significant reduction in serum BALP was observed in the participants consuming the hemp seed pasta compared to control group (−2.8 ± 3.2 µg/L vs. 1.1 ± 4.3 µg/L; p = 0.04). In the Saos-2 cell line, hemp seed extract also upregulated Wnt/β-catenin and Erk1/2 pathways (p = 0.02 and p = 0.03) and osteoblast differentiation markers (e.g., ALP, OC, RUNX2, and COL1A) and downregulated RANKL (p = 0.02), compared to the control. Our study demonstrated that hemp seed can improve pain symptoms in patients with osteoarthritis undergoing arthroplasty surgery and also improves bone metabolism both in humans and in vitro. However, more clinical studies are needed to confirm our preliminary findings.

This work aims at (1) assessing the potential of repurposing simvastatin (SV) to support the most common therapies against melanoma and (2) developing an innovative topical adhesive film, composed by chitosan-coated nanostructured lipid carriers (Ch-NLC) used as drug vehicle. A factorial design approach was employed as the basis for the formulation development. Optimized Ch-NLC displayed a particle size of 108 ± 1 nm, a polydispersity index of 0.226, a zeta potential of 17.0 ± 0.6 mV, as well as an entrapment efficiency of 99.86 ± 0.08%, and SV loading of 14.99 ± 0.01%. The performance of SV-Ch-NLC films was assessed in terms of release, permeation, and adhesion, as critical quality attributes. Cutaneous tolerability and in vitro cytotoxicity studies were performed to warrant film safety and drug effectiveness, respectively. The topical films provided a sustained release kinetic profile of SV and were classified as nonirritant systems. The encapsulation of SV increased cytotoxicity in melanoma cells. The key role of squalene as nanostructuring agent of the lipid nanoparticle matrix and as permeation enhancer was highlighted, suggesting its key action for potentiating skin permeation and uptake into melanoma cells. Topical SV-Ch-NLC films are thus able to provide an in situ extended drug delivery and useful as coadjuvant treatment of melanoma skin lesions.

Background: Bergamot polyphenolic fraction (PF) extract exerts a beneficial against liver steatosis. However, the fundamental processes underlying this beneficial effect of bergamot PF remain elusive. In this work, we examined the effect of bergamot PF extract on 2D and 3D hepatocyte cultures. Material and Methods: We evaluated the effect of bergamot PF in 2D and 3D cultures from rat, human hepatoma cells, and human primary hepatocytes. Results: In 2D cell culture, we demonstrated that incubation with bergamot PF decreases intracellular lipid content and is associated with an increase in expression levels of ß-oxidation genes (Acox1, Pparα, and Ucp2) and lipophagy (Atg7). Moreover, we confirm this effect on 3D spheroids and organoids. Conclusion: Incubation with bergamot PF reduces intracellular lipid neutral fat potentially by increasing intracellular pathways related to beta-oxidation.

BackgroundMost studies focused on the benefits of lycopene on serum lipids but no studies have been specifically designed to assess the role of a tomato sauce from vine-ripened tomatoes on patients affected by polygenic hypercholesterolemia. The aim of this study was to compare the lipid-lowering effect of a novel functional tomato sauce with a well-known functional food with a lipid-lowering effect, i.e. a sterol-enriched yogurt.MethodsIn this cross-over study, we evaluated a population of 108 ambulatory patients affected by polygenic hypercholesterolemia of both gender, who were allocated to a tomato sauce (namely OsteoCol) 150 ml/day or a sterol-enriched yogurt (containing sterols 1.6 g/die) treatment, for 6 weeks. Carotenoids content was 3.5 mg per gram of product. We measured serum lipids and creatinine and transaminases at basal and follow-up visit.ResultsA total of 91 subjects completed the protocol. A significant difference in LDL-cholesterol change was found between participants taking yogurt, tomato sauce (high adherence) and tomato sauce (low adherence) (− 16; − 12; + 8 mg/dl respectively; p ConclusionA novel functional tomato sauce from vine-ripened tomatoes compares favourably with a commercialised sterol-enriched yogurt in term of absolute LDL-cholesterol change. Intake of a tomato sauce with a high carotenoid content may support treatment of patients affected by common hypercholesterolemia. The present study has various limitations. The presence of other dietary components, which may have influenced the results, cannot be ruled out. Of course, these results cannot be extrapolated to other populations. Furthermore, there was a low adherence rate in the tomato sauce group. Moreover, we did not report serum carotenoids data.Trial registration: ID: 13244115 on the ISRCTN registry, retrospectively registered in 2019-5-14. URL:http://www.isrctn.com/ISRCTN13244115

Despite the abundance of studies on the beneficial effects of a fiber rich diet as well as polyphenols deriving from Citrus fruits on postprandial serum glucose and insulin, clinical evidence on their synergic effects on healthy subjects have never been published. We aimed to investigate the feasibility of a new dietary approach in controlling glucose and insulin response at breakfast time by testing a brioche enriched with wheat bran and bergamot fiber.We enrolled 11 healthy volunteers in a cross-over study. Participants consumed a classic brioche at breakfast and our functional brioche, containing wheat bran and bergamot fiber, on another day. Vital functions, biochemical parameters (including glucose and insulin), anthropometric measurements as well as resting energy expenditure and fat oxidation were evaluated before and after the intake of both meals.The mean age was ~25 years. The mean BMI was 23.5 kg/mThe association of wheat bran and bergamot fiber significantly influences glucose metabolism and may exert insulin-like effects on healthy volunteers. If confirmed, berga-brioche would be a useful tool in preventing diabetes and controlling the glycometabolic status of type 2 diabetic patients.

BackgroundThere are several effective therapies for osteoporosis but these agents might cause serious adverse events. Lycopene intake could prevent bone loss, however studies on its effects on bone are scarce. Our aim was to investigate the effects of lycopene on osteoblast cells as well as bone mineral density and bone turnover markers in postmenopausal women.MethodsWe investigated the effect of lycopene on the Wnt/β-catenin and ERK 1/2 pathways, RUNX2, alkaline phosphatase, RANKL and COL1A of Saos-2. We also carried out a pilot controlled clinical study to verify the feasibility of an approach for bone loss prevention through the intake of a lycopene-rich tomato sauce in 39 postmenopausal women.ResultsLycopene 10 µM resulted in higher β-catenin and phERK1/2 proteinVsthe vehicle (p = 0.04 and p = 0.006). RUNX2 and COL1A mRNA was induced by both 5 and 10 µM doses (p = 0.03; p = 0.03 and p = 0.03; p = 0.05) while RANKL mRNA was reduced (p ConclusionsLycopene activates the WNT/β-catenin and ERK1/2 pathways, upregulates RUNX2, alkaline phosphatase, COL1A and downregulates RANKL Saos-2. These processes contributed to prevent bone loss in postmenopausal women.

Identifying and quantifying the beneficial molecules contained in nutraceuticals is essential to predict the effects derived from their consumption. This study explores a cheap and rapid method for quantifying lycopene content from a semi-solid matrix. In addition, it compares the in vitro effects of the extracts obtained from different tomato sauces available on the local market with Osteocol®, a patented tomato sauce from southern Italy. We performed a liquid extraction of lycopene using suitable solvents. The lycopene extracted was encapsulated in surfactant micelles and finally tested in vitro on Saos-2 cells. The effects exerted by lycopene on ALP and Wnt/β-catenin pathways were investigated by Western blotting. Hexane was found to be the best solvent for lycopene extraction. Spectrophotometrical and HPLC analyses showed similar trends. Osteocol® contained 39 ± 4 mg lycopene per 100 g of sauce, while the best commercial product contained 19 ± 1 mg/100 g. The Osteocol® lycopene extract increased ALP and β-catenin protein expressions in a dose-dependent manner, also showing statistically significant results (p < 0.05 respectively). In conclusion, despite both techniques showing similar final results, UV/VIS spectrophotometer is preferable to HPLC due to its cheap, rapid, and accurate results, as well as for the opportunity to analyze lycopene-loaded micelles. The extraction and release of lycopene to bone cells positively influences the differentiation of osteoblasts and increases the expression of the ALP and β-catenin proteins. As a consequence, as a lycopene-rich sauce, Osteocol® represents a useful supplement in the prevention of osteoporosis compared to its commercial competitors.

Polyethylene glycol (PEG)-phospholipids in long-circulating liposomes cause non-specific immune reactions, mainly attributable to negatively-charged phosphoryl s at the interface of PEG and phospholipid. We investigated a novel lipopolymer, by which a superhydrophilic polymer (SHP) is conjugated to a non-phospholipid N1-(2-aminoethyl)-N4-hexadecyl-2-tetradecylsuccinamide (HDAS). The modification of preformed liposomes HDAS-SHP, HDAS-PEG2000, and DSPE-PEG2000 were performed by post-insertion techniques. The efficiency of post-insertion and desorption rates, from the liposome surface, were determined. HDAS-SHP micelles showed highly positive zeta potential (+28.4 mV), zeta potentials of DSPE-PEG2000 and HDAS-PEG2000 micelles were &minus, 34.4 mV, and &minus, 3.7 mV, respectively. Critical micelle concentration predicted amphiphilicity of HDAS-SHP (CMC 2.58 &micro, M) as close to that of DSPE-PEG2000 (CMC 2.44 &micro, M). Both HDAS-SHP and HDAS-PEG2000 post-inserted with comparable efficiency (79%, and 73%, respectively), but noticeably lower than DSPE-PEG2000 (90%). The desorption rate of HDAS-SHP was close to that of DSPE-PEG2000 (0.53%/h, and 0.45%/h, respectively), the desorption rate for HDAS-PEG2000 was slightly more at 0.67%/h. Compared to plain liposomes, both HDAS-SHP- and DSPE-PEG2000-liposomes showed significant leakage of encapsulated Na-fluorescein isothiocyanate (FITC) upon incubation with serum. At the same time, both modified liposomes were found to suppress serum levels of the complement proteins, Bb and C4d. We infer that HDAS-SHP is a viable alternative to commonly-used PEG-phospholipid derivatives for stealth purposes.

Sclareol (labd‑14‑ene‑8,13‑diol), a phytochemical compound belonging to labdane-type diterpenes, has recently attracted noteworthy attention because of its peculiar pharmacological properties. The foremost obstacle to an efficacious application and use of this molecule is its unfavorable bioavailability due to its poor aqueous solubility. In this investigation sclareol was encapsulated within PLGA nanoparticles with the aim of favoring its administration in physiological media, increasing its anticancer activity and obtaining a stable colloidal formulation. These nanoparticles containing sclareol were characterized by a mean diameter of 100–150 nm, a narrow size distribution and a negative surface charge. The active compound was efficiently retained by the polymeric structure and did not induce any physical destabilization. The coating of the PLGA nanoparticles with hyaluronic acid (1.5 MDa) increased the antitumor efficacy of the encapsulated drug against human breast cancer cells expressing the hyaluronan receptors (MCF-7 and MDA-MB468) while a similar pharmacological effect was obtained on human colon carcinoma cells (CaCo-2). CLSM analysis demonstrated the intracellular localization of fluorescent nanosystems after 3 h incubation.

Context: The role of dietary patterns in the prevention of osteoporosis has been investigated in many studies, but few have examined the association between consumption of specific food and whole-body (WB) bone mineral density (BMD). Recent evidence suggests that whole eggs contain bioactive compounds that could have beneficial effects on BMD. BMD is also expressed as the T-score, which is used for the clinical diagnosis of osteoporosis and to evaluate the effectiveness of drugs. Aims: We conducted a study to assess the association between eggs consumption and bone density in a population of the elderly. Settings and Design: This cross-sectional study included 176 individuals of both genders and aged ≥65 years. Subjects and Methods: Egg intake was ascertained by a combination of dietary intake assessment, and a dual X-ray absorptiometry scan was performed to measure WB T-score. Results: In our study, among all the food groups and nondietary factors evaluated, we find a positive association between the WB T-score and egg consumption (B = 0.02; P = 0.02), gender (B = 0.85; P < 0.001), and body mass index (B = 0.04; P = 0.03). Multiple fractures were associated with the daily intake of eggs (B = ‒0.26; P = 0.02) and high-density lipoprotein-cholesterol (B = 0.09; P = 0.03). Conclusions: This study provides novel evidence of a positive link between whole egg consumption and bone health. If results observed in this study will be confirmed through future randomized controlled trials, whole eggs may represent a viable strategy to prevent osteoporosis and reduce the risk of fractures in the elderly.

The insertion of specific derivatives into pre-formed colloidal systems has been shown to be a useful method for modifying their pharmacokinetic characteristics and biodistribution profiles. In this experimental work the effect of the post-insertion of different PEG-derivatives into pre-formed 100-nm liposomes made up of various lipid mixtures (DMPC, DPPC, DOPC, DSPC and cholesterol at different molar ratios) was investigated. The vesicles were incubated with increasing amounts of DSPE-mPEG2000 as sterically stabilized micelles (5, 10 and 15% w/w with respect to the liposomal lipid mixture) in order to favour the insertion of the PEG-lipid into the liposomal bilayer. The colloidal formulations were characterized by photo-correlation spectroscopy; the DSPE-mPEG2000 integrated into the pre-formed liposomes was demonstrated by means of field flow fractionation while the amount of post-inserted compound was quantified using a suitable spectrophotometric assay (I2 assay). Similar investigations have been performed using PEG-derivatives characterized by a different molecular weight. The physico-chemical properties of the various liposomal formulations were influenced by the post-insertion of PEG-derivatives. The lipid mixture made up of saturated phospholipids and cholesterol proved to be the best, post-insertion (P.I.E.). The post-insertion technique may be a suitable approach to be used in personalized (nano)medicine.

Studies have fully demonstrated that a diet rich in fruit and vegetables may reduce the incidence of tumors. In particular, Grape Seed Extract (GSE) has been shown to carry on chemopreventive and antitumor activity thanks to the numerous beneficial substances it contains. The purpose of this work was to create a biocompatible matrix containing GSE in order to obtain microparticles able to modulate its biopharmaceutical parameters. The spray-drying technique was chosen in order to realize chitosan microparticles characterized by a mean diameter of 4–10 μm and a positive surface charge that decreased after GSE encapsulation. The evaluation of the pharmacological activity of the GSE and these GSE-loaded chitosan microparticles on different cancer cells together with CLSM investigation evidenced an increase in the antitumor effect promoted by the polysaccharide as a consequence of the enhanced cell interaction. Therefore GSE-loaded chitosan microparticles may be an innovative drug delivery system useful for the treatment of certain cancer-related diseases.

All-trans retinoic acid (ATRA) is an anti-tumor compound, exerting different anti-cancer effects on different types of cancer cells. Unfortunately, retinoids are also characterized by certain side effects following systemic administration, such as the burning of skin and general malaise. The highly variable degree of bioavailability of ATRA plus its tendency to induce its own destruction through metabolic degradation following oral treatment necessitate the development of alternative formulations. The aim of this work is to evaluate the physico-chemical properties of unilamellar, ATRA-containing liposomes and to investigate the cytotoxic activity of this potential nanomedicine on human thyroid carcinoma cells. Liposomes made up of DPPC/Chol/DSPE-mPEG2000 (6:3:1 molar ratio), characterized by a mean diameter of ∼200nm, a polydispersity index of 0.1 and a negative surface charge, were used as ATRA-carriers and their antiproliferative efficacy was investigated in comparison with the free drug on three different human thyroid carcinoma cell lines (PTC-1, B-CPAP, and FRO) through MTT-testing. The liposomes protected the ATRA against photodegradation and increased its antiproliferative properties due to the improvement of its cellular uptake. ATRA-loaded liposomes could be a novel formulation useful for the treatment of anaplastic thyroid carcinoma.