Wound healing is a complicated process, and the effective management of wounds is a major challenge. Natural herbal remedies have now become fundamental for the management of skin disorders and the treatment of skin infections due to the side effects of modern medicine and lower price for herbal products. The aim of the present study is to summarize the most recent in vitro, in vivo, and clinical studies on major herbal preparations, their phytochemical constituents, and new formulations for wound management. Research reveals that several herbal medicaments have marked activity in the management of wounds and that this activity is ascribed to flavonoids, alkaloids, saponins, and phenolic compounds. These phytochemicals can act at different stages of the process by means of various mechanisms, including anti-inflammatory, antimicrobial, antioxidant, collagen synthesis stimulating, cell proliferation, and angiogenic effects. The application of natural compounds using nanotechnology systems may provide significant improvement in the efficacy of wound treatments. Increasing the clinical use of these therapies would require safety assessment in clinical trials.

STUDY QUESTION Is SIRT1 involved in the oxidative stress (OS) response in mouse oocytes? SUMMARY ANSWER SIRT1 plays a pivotal role in the adaptive response of mouse germinal vesicle (GV) oocytes to OS and promotes a signalling cascade leading to up-regulation of the MnSod gene. WHAT IS KNOWN ALREADY OS is known to continuously threaten acquisition and maintenance of oocyte developmental potential during in vivo processes and in vitro manipulations. Previous studies in somatic cells have provided strong evidence for the role of SIRT1 as a sensor of the cell redox state and a protector against OS and aging. STUDY DESIGN, SIZE, DURATION GV oocytes obtained from young (4–8 weeks) and reproductively old (48–52 weeks) CD1 mice were blocked in the prophase stage by 0.5 µM cilostamide. Groups of 30 oocytes were exposed to 25 µM H₂O₂ and processed following different times for the analysis of intracellular localization of SIRT1 and FOXO3A, and evaluation of Sirt1, miRNA-132, FoxO3a and MnSod gene expression. Another set of oocytes was cultured in the presence or absence of the SIRT1-specific inhibitor Ex527, and exposed to H₂O₂ in order to assess the involvement of SIRT1 in the activation of a FoxO3a-MnSod axis and ROS detoxification. In the last part of this study, GV oocytes were maturated in vitro in the presence of different Ex527 concentrations (0, 2.5, 5, 10, 20 µM) and assessed for maturation rates following 16 h. Effects of Ex527 on spindle morphology and ROS levels were also evaluated. PARTICIPANTS/MATERIALS, SETTING, METHODS SIRT1 and FOXO3A intracellular distribution in response to OS was investigated by immunocytochemistry. Real-time RT–PCR was employed to analyse Sirt1, miR-132, FoxO3a and MnSod gene expression. Reactive oxygen species (ROS) production was evaluated by in vivo measurement of carboxy-H₂DCF diacetate labelling. Spindle and chromosomal distribution in in vitro matured oocytes were analysed by immunocytochemistry and DNA fluorescent labelling, respectively. MAIN RESULTS AND THE ROLE OF CHANCE Specific changes in the intracellular localization of SIRT1 and up-regulation of Sirt1 gene were detected in mouse oocytes in response to OS. Moreover, increased intracellular ROS were observed when SIRT1 activity was inhibited by Ex527. In aged oocytes Sirt1 was expressed more than in young oocytes but SIRT1 protein was undetectable. Upon OS, significant changes in miR-132 micro-RNA, a validated Sirt1 modulator, were observed. A negative correlation between Sirt1 mRNA and miR-132 levels was observed when young oocytes exposed to OS were compared with young control oocytes, and when aged oocytes were compared with young control oocytes. FoxO3a and MnSod transcripts were increased upon OS with the same kinetics as Sirt1 transcripts, and up-regulation of MnSod gene was prevented by oocyte treatment with Ex527, indicating that SIRT1 acts upstream to the FoxO3a-MnSod axis. Finally, the results of the in vitro maturation assay suggested that SIRT1 might be involved in oocyte maturation by regulating the redox state and ensuring normal spindle assembly. LIMITATIONS, REASONS FOR CAUTION The main limitation of this study was the absence of direct quantification of SIRT1 enzymatic activity due to the lack of an appropriately sensitive method. WIDER IMPLICATIONS OF THE FINDINGS The present findings may provide a valuable background for studying the regulation of SIRT1 during oogenesis and its relevance as a sensor of oocyte redox state and energy status. The antioxidant response orchestrated by SIRT1 in oocytes seems to decrease with aging. This suggests that SIRT1 could be an excellent pharmacological target for improving oocyte quality and IVF outcome in aging or aging-like diseases. STUDY FUNDING/COMPETING INTEREST(S) The work was supported by the Ministero dell'Università e della Ricerca Scientifica (MIUR) to C.T., F.A., C.D., A.M.D. The authors declare no conflict of interest.

In search for strategies aimed at preventing oxidative threat to female fertility, a possible role of sirtuins has emerged. Sirtuins (silent information regulator 2 (Sir2) proteins), NAD⁺dependent enzymes with deacetylase and/or mono-ADP-ribosyltransferase activity, are emerging as key antiaging molecules and regulators in many diseases. Recently, a crucial role for SIRT1 and SIRT3, the main components of sirtuin family, as sensors and guardians of the redox state in oocytes, granulosa cells, and early embryos has emerged. In this context, the aim of the present review is to summarize current knowledge from research papers on the role of sirtuins in female fertility with particular emphasis on the impairment of SIRT1 signalling with oocyte aging. On this basis, the authors wish to build up a framework to promote research on the possible role of sirtuins as targets for future strategies for female fertility preservation.

Crocus sativusL. extracts (saffron) are rich in carotenoids. Preclinical studies have shown that dietary intake of carotenoids has antitumor effects suggesting their potential preventive and/or therapeutic roles. We have recently reported that saffron (SE) and crocin (CR) exhibit anticancer activity by promoting cell cycle arrest in prostate cancer (PCa) cells. It has also been demonstrated that crocetin esters are produced after SE gastrointestinal digestion by CR hydrolysis. The aim of the present report was to investigate if SE, crocetin (CCT), and CR affectedin vivotumor growth of two aggressive PCa cell lines (PC3 and 22rv1) which were xenografted in male nude mice treated by oral gavage with SE, CR, and CCT. We demonstrated that the antitumor effects of CCT were higher when compared to CR and SE and treatments reverted the epithelial-mesenchymal transdifferentiation (EMT) as attested by the significant reduction of N-cadherin and beta-catenin expression and the increased expression of E-cadherin. Additionally, SE, CR, and CCT inhibited PCa cell invasion and migration through the downmodulation of metalloproteinase and urokinase expression/activity suggesting that these agents may affect metastatic processes. Our findings suggest that CR and CCT may be dietary phytochemicals with potential antitumor effects in biologically aggressive PCa cells.

Introduction: Cancer is a disorder which has a powerful impact on the quality life and life expectancy despite the increase in drugs and treatments available for cancer patients. Moreover, many new therapeutic options are known to have adverse reactions without any improvement in outcome than before. Nowadays, natural products or plant derivatives are used as chemoprevention drugs and chemotherapy is the new approach that uses specific cell premalignant transformation in the malignant form. Natural substances derived from plants, such as polyphenols, flavonoids, carotenoids, alkaloids and others, can be biologically active and have a wide spectrum of effects. The protective effects of Saffron carotenoids (crocin and crocetin) have been extensively studied mainly for their antioxidant properties, however, they have various other biological activities including tumor growth inhibition with the induction of cell death.Methods: The relevant information on Saffron and its carotenoids was collected from scientific databases (such as PubMed, Web of Science, Science Direct). To identify all published articles in relation to saffron, crocin and crocetin, in different types of cancer, no language restriction has been used.Results: To date, crossing the words saffron and cancer, approximately 150 articles can be found. If crossing is made between crocin and cancer, approximately 60 articles can be found. With the crossing between crocetin and cancer, the number is approximately 55, while between carotenoids and cancer, the number exceeds 16.000 reports. In all the papers published to date, there are evidences that saffron and its carotenoids exert chemopreventive activity through anti-oxidant activity, cancer cells apoptosis, inhibition of cell proliferation, enhancement of cell differentiation, modulation of cell cycle progression and cell growth, modulation of tumor metabolism, stimulation of cell-to-cell communication and immune modulation.Conclusion: Here, we have tried to offer an up-to-date overview of pre-clinical experimental investigations on the potential use of the main carotenoids of saffron in tumor models and focus the attention on the molecular mechanisms involved.

Mitochondria act as hubs of numerous metabolic pathways. Mitochondrial dysfunctions contribute to altering the redox balance and predispose to aging and metabolic alterations. The sirtuin family is composed of seven members and three of them, SIRT3-5, are housed in mitochondria. They catalyze NAD+-dependent deacylation and the ADP-ribosylation of mitochondrial proteins, thereby modulating gene expression and activities of enzymes involved in oxidative metabolism and stress responses. In this context, mitochondrial sirtuins (mtSIRTs) act in synergistic or antagonistic manners to protect from aging and aging-related metabolic abnormalities. In this review, we focus on the role of mtSIRTs in the biological competence of reproductive cells, organs, and embryos. Most studies are focused on SIRT3 in female reproduction, providing evidence that SIRT3 improves the competence of oocytes in humans and animal models. Moreover, SIRT3 protects oocytes, early embryos, and ovaries against stress conditions. The relationship between derangement of SIRT3 signaling and the imbalance of ROS and antioxidant defenses in testes has also been demonstrated. Very little is known about SIRT4 and SIRT5 functions in the reproductive system. The final goal of this work is to understand whether sirtuin-based signaling may be taken into account as potential targets for therapeutic applications in female and male infertility.