In Vitro Antioxidant Activity and In Vivo Topical Efficacy of Lipid Nanoparticles Co-Loading Idebenone and Tocopheryl Acetate

Idebenone (IDE) is a strong antioxidant that has been proposed for the treatment of skin disorders, including skin ageing. Unfavorable physico-chemical properties make IDE a poor skin permeant where effectiveness could be improved by its loading into suitable delivery systems such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC). In this work, we designed novel IDE-loaded NLC containing tocopheryl acetate (VitE) as a liquid component to obtain a synergic effect between IDE and VitE. The resulting NLC showed small particle sizes (24-42 nm), low polydispersity indices (<0.300), good stability, and were assessed for their in vitro antioxidant activity and in vivo topical effects. IDE-loaded SLN and NLC showed a high antioxidant activity in in vitro assays (DPPH and reducing power method) and provided a similar and significant protection from oxidative stress of fibroblast cells, HS-68, exposed to UV light. After a two-week topical treatment of human volunteers with gels containing IDE-loaded SLN or NLC, a similar increase in skin hydration was observed, while IDE NLC reduced skin pigmentation to a greater extent than IDE SLN. These results suggest that co-loading IDE and VitE into NLC could be a promising strategy to obtain topical formulations with improved photo-protection

Compensation Committee Quality and Effective Executive Remuneration

Grounding in the agency theory, this paper questions whether high quality compensation committee influences the design of executive remuneration towards the alignment of the contrasting interests between managers and shareholders. Relying on a comprehensive approach that captures the compensation committee quality based on different attributes (i.e. independence, interlocking directorates, directors appointed by minorities) we conduct a two-step empirical analysis. First, we illustrate the evolution over time of the stock option plan characteristics and construct an illustrative diagram that shows the linkages between the attributes of the compensation committee quality and the elements of the option plans. Second, we run a probit regression analysis to deeply investigate the picture emerging from the diagram. Our results document that the quality of compensation committee significantly affects the assignment of incentive stock option plans. The paper evidence advances the knowledge in the literature on compensation committee and executive remuneration, by highlighting that structural characteristics of the committee other than independence of its members play a pivotal role in writing effective remuneration contracts for the executives. Our findings are also useful for investors and policymakers

the influence of blockholders bondholders and families on the venturers accounting behavior

Relying on the opportunistic view of contracting theory, the paper explores the influence of blockholders, bondholders and families on the managerial accounting for interests in jointly controlled entities. In particular, it assumes that the equity method is an opportunistic accounting choice as it improves firm performance and induces managerial self-dealing rather than efficient contracting. The paper examines a sample of Italian listed companies holding interests in jointly controlled entities through a logistic regression analysis. Findings show that the family influence encourages the opportunistic choice of equity method, while the monitoring role played by blockholders and bondholders discourages the use of the performance-improving technique. The research contributes to the literature on contracting theory and corporate governance and has also practical implications for evaluating the appropriateness of IFRS 11.</p

Lentils biodiversity: the characterization of two local landraces

A multi-disciplinary approach was used to characterize two autochthonous lentil landraces from Molise region (Central Italy). Different mature seed populations for each landrace were provided by the Molise Germoplasm Bank at the University of Molise (Pesche, Italy), and analyzed at the morphological and molecular (DNA and protein) levels. Nuclear ISSR markers were used to assess genetic differences, whereas phenotypic variability was detected by biochemical (proteomics) and morphological analyses. The genetic and phenotypic diversity of the two lentil landraces were well assessed in relation to their geographical provenance, supporting further studies to identify landrace markers

Hyperphosphorylation of JNK-interacting Protein 1, a Protein Associated with Alzheimer Disease

The c-Jun N-terminal kinase (JNK) group of mitogen-activated protein (MAP) kinases are activated by pleiotropic signals including environmental stresses, growth factors, and hormones. JNK-interacting protein 1 (JIP1) is a scaffold protein that assembles and facilitates the activation of the mixed lineage kinase-dependent JNK module and also establishes an interaction with beta-amyloid precursor protein that has been partially characterized. Here we show that, similarly to other proteins involved in various neurological diseases, JIP1 becomes hyperphosphorylated following activation of stress-activated and MAP kinases. By immobilized metal affinity chromatography and a combined microcapillary LC/MALDI-TOF/ESI-ion trap mass spectrometry approach, we identified 35 sites of mitotic phosphorylation within JIP1, among which eight were present within (Ser/Thr)-Pro sequence. This motif is modified by various kinases in aggregates of the microtubule-associated protein tau, which generates typical intraneuronal lesions occurring in Alzheimer disease. Most of the post-translational modifications found were located within the JNK, MAP kinase kinase, and RAC-alpha Ser/Thr protein kinase binding regions; no modifications occurred in protein Src homology 3 and phosphotyrosine interaction domains, which are essential for binding to kinesin, beta-amyloid precursor protein, and MAP kinase kinase kinase. Protein phosphorylation is known to affect stability and protein-protein interactions. Thus, the findings that JIP1 is extensively phosphorylated after activation of stress-activated and MAP kinases indicate that these signaling pathways might modulate JIP1 signaling by regulating its stability and association with some, but not all, interacting proteins

Cost-effectiveness analysis of ovarian tissue cryopreservation and transplantation for preservation of fertility in post-pubertal oncological women submitted to high-risk gonadotoxic chemotherapy

Objective: To study the economic impact of ovarian tissue cryopreservation and transplantation (OTC) in post-pubertal patients who underwent high-risk gonadotoxic chemotherapy. Methods: A decision tree model was used to determine the live birth rate and cost-effectiveness of OTC versus non-OTC. The incremental cost-effectiveness ratio (ICER) was calculated. A sensitivity analysis was performed under the assumption that the costs of ovarian cortex retrieval, cryopreservation, and storage for patients with cancer might be covered by the national health system or health insurance. Results: Patients had the greatest probability of achieving live birth after high-risk chemotherapy when they underwent OTC versus non-OTC. Although cryopreservation of ovarian tissue results in higher live birth rates, it is always more expensive. Cost-effectiveness increases when the majority of patients completes the path of tissue cryopreservation plus transplantation after 5&nbsp;years. Conclusion: Although OCT has been demonstrated as a procedure for effective fertility preservation in fertility-age women with cancer, no cost-effectiveness analysis has been performed until now. This model could help healthcare systems to allocate coverage for OCT

Effects of Dietary Supplementation with Honeybee Pollen and Its Supercritical Fluid Extract on Immune Response and Fillet’s Quality of Farmed Gilthead Seabream (Sparus aurata)

The awareness of the correlation between administered diet, fish health and products’ quality has led to the increase in the research for innovative and functional feed ingredients. Herein, a plant-derived product rich in bioactive compounds, such as honeybee pollen (HBP), was includ-ed as raw (HBP) and as Supercritical Fluid Extracted (SFE) pollen (HBP_SFE) in the diet for gilt-head seabream (Sparus aurata). The experiment was carried out on 90 fish with an average body weight of 294.7 ± 12.8 g, divided into five groups, according to the administration of five diets for 30 days: control diet (CTR); two diets containing HBP at 5% (P5) and at 10% (P10) level of in-clusion; two diets containing HBP_SFE, at 0.5% (E0.5) and at 1% (E1) level of inclusion. Their ef-fects were evaluated on 60 specimens (336.2 ± 11.4 g average final body weight) considering the fish growth, the expression of some hepatic genes involved in the inflammatory response (il-1β, il-6 and il-8) through quantitative real-time PCR, and physico-chemical characterization (namely color, texture, water holding capacity, fatty acid profile and lipid peroxidation) of the fish fillets monitored at the beginning (day 0) and after 110 days of storage at −20 °C. The results obtained showed that the treatment with diet E1 determined the up-regulation of il-1β, il-6, and il-8 (p &lt; 0.05); however, this supplementation did not significantly contribute to limiting the oxidative stress. Nevertheless, no detrimental effect on color and the other physical characteristics was observed. These results suggest that a low level of HBP_SFE could be potentially utilized in aq-uaculture as an immunostimulant more than an antioxidant, but further investigation is neces-sary

Case Report: Rare Homozygous RNASEH1 Mutations Associated With Adult-Onset Mitochondrial Encephalomyopathy and Multiple Mitochondrial DNA Deletions

Mitochondrial DNA (mtDNA) maintenance disorders embrace a broad range of clinical syndromes distinguished by the evidence of mtDNA depletion and/or deletions in affected tissues. Among the nuclear genes associated with mtDNA maintenance disorders, RNASEH1 mutations produce a homogeneous phenotype, with progressive external ophthalmoplegia (PEO), ptosis, limb weakness, cerebellar ataxia, and dysphagia. The encoded enzyme, ribonuclease H1, is involved in mtDNA replication, whose impairment leads to an increase in replication intermediates resulting from mtDNA replication slowdown. Here, we describe two unrelated Italian probands (Patient 1 and Patient 2) affected by chronic PEO, ptosis, and muscle weakness. Cerebellar features and severe dysphagia requiring enteral feeding were observed in one patient. In both cases, muscle biopsy revealed diffuse mitochondrial abnormalities and multiple mtDNA deletions. A targeted next-generation sequencing analysis revealed the homozygous RNASEH1 mutations c.129-3C&gt;G and c.424G&gt;A in patients 1 and 2, respectively. The c.129-3C&gt;G substitution has never been described as disease-related and resulted in the loss of exon 2 in Patient 1 muscle RNASEH1 transcript. Overall, we recommend implementing the use of high-throughput sequencing approaches in the clinical setting to reach genetic diagnosis in case of suspected presentations with impaired mtDNA homeostasis