Exosome levels in human body fluids: A tumor marker by themselves?

Despite considerable research efforts, the finding of reliable tumor biomarkers remains challenging and unresolved. In recent years a novel diagnostic biomedical tool with high potential has been identified in extracellular nanovesicles or exosomes. They are released by the majority of the cells and contain detailed molecular information on the cell of origin including tumor hallmarks. Exosomes can be isolated from easy accessible body fluids, and most importantly, they can provide several biomarkers, with different levels of specificity. Recent clinical evidence shows that the levels of exosomes released into body fluids may themselves represent a predictive/diagnostic of tumors, discriminating cancer patients from healthy subjects. The aim of this review is to highlight these latest challenging findings to provide novel and groundbreaking ideas for successful tumor early diagnosis and follow-up

Spironolactone treatment attenuates vascular dysfunction in type 2 diabetic mice by decreasing oxidative stress and restoring NO/GC signaling

Type 2 diabetes (DM2) increases the risk of cardiovascular disease. Aldosterone, which has pro-oxidative and pro-inflammatory effects in the cardiovascular system, is positively regulated in DM2. We assessed whether blockade of mineralocorticoid receptors (MR) with spironolactone decreases reactive oxygen species (ROS)-associated vascular dysfunction and improves vascular nitric oxide (NO) signaling in diabetes. Leptin receptor knockout [LepRdb/LepRdb (db/db)] mice, a model of DM2, and their counterpart controls [LepRdb/LepR+, (db/+) mice] received spironolactone (50 mg/kg body weight/day) or vehicle (ethanol 1%) via oral per gavage for 6 weeks. Spironolactone treatment abolished endothelial dysfunction and increased endothelial nitric oxide synthase (eNOS) phosphorylation (Ser1177) in arteries from db/db mice, determined by acetylcholine-induced relaxation and Western Blot analysis, respectively. MR antagonist therapy also abrogated augmented ROS-generation in aorta from diabetic mice, determined by lucigenin luminescence assay. Spironolactone treatment increased superoxide dismutase-1 and catalase expression, improved sodium nitroprusside and BAY 41-2272-induced relaxation, and increased soluble guanylyl cyclase (sGC) β subunit expression in arteries from db/db mice. Our results demonstrate that spironolactone decreases diabetes-associated vascular oxidative stress and prevents vascular dysfunction through processes involving increased expression of antioxidant enzymes and sGC. These findings further elucidate redox-sensitive mechanisms whereby spironolactone protects against vascular injury in diabetes

Euphorbia characias Extract: Inhibition of Skin Aging-Related Enzymes and Nanoformulation

Plant extracts have long served as important sources of bioactive compounds, and they are currently the focus of extensive research in the development of novel preventive and therapeutic strategies. However, their health benefits are often limited by low bioavailability. Nanoparticle delivery systems can represent a solution to such limitations. Euphorbia characias is a Mediterranean shrub known to have biological activities, such as inhibiting tyrosinase and showing a potential role as a skin-whitening agent. In this study, an ethanolic extract from E. characias leaves was tested for its inhibitory activity on skin-related enzymes, such as elastase, collagenase, and hyaluronidase, and for sun protection factors. Moreover, the extract was formulated in phospholipid vesicles to improve its local bioavailability and applicability. The vesicles were characterized by size, surface charge, storage stability, and entrapment efficiency. The nanoformulation was also evaluated for antioxidant activity and assayed for cytocompatibility and anti-tyrosinase activity in melanoma cells. Our findings demonstrated that the extract has a photo-protective effect and enzyme-inhibitory properties. E. characias nanoformulation was also cytocompatible and improved the extract’s activity in the cells, suggesting a potential skin application for antimelanogenic treatments and confirming the key role of nanotechnological approaches to maximize plant extract’s potentialities

Forensic applications of micro-computed tomography: a systematic review

Purpose: The aim of this systematic review was to provide a comprehensive overview of micro-CT current applications in forensic pathology, anthropology, odontology, and neonatology. Methods: A bibliographic research on the electronic databases Pubmed and Scopus was conducted in the time frame 01/01/2001–31/12/2021 without any language restrictions and applying the following free-text search strategy: “(micro-computed tomography OR micro-CT) AND (forensic OR legal)”. The following inclusion criteria were used: (A) English language; (B) Application of micro-CT to biological and/or non-biological materials to address at least one forensic issue (e.g., age estimation, identification of post-mortem interval). The papers selected by three independent investigators have been then classified according to the investigated materials. Results: The bibliographic search provided 651 records, duplicates excluded. After screening for title and/or abstracts, according to criteria A and B, 157 full-text papers were evaluated for eligibility. Ninety-three papers, mostly (64) published between 2017 and 2021, were included; considering that two papers investigated several materials, an overall amount of 99 classifiable items was counted when referring to the materials investigated. It emerged that bones and cartilages (54.55%), followed by teeth (13.13%), were the most frequently analyzed materials. Moreover, micro-CT allowed the collection of structural, qualitative and/or quantitative information also for soft tissues, fetuses, insects, and foreign materials. Conclusion: Forensic applications of micro-CT progressively increased in the last 5 years with very promising results. According to this evidence, we might expect in the near future a shift of its use from research purposes to clinical forensic cases

Sperm whale echolocation behaviour reveals a directed, prior-based search strategy informed by prey distribution

The fieldwork was funded by a grant from the Carlsberg Foundation to B. Møhl and ONR, SERDP and FNU grants to MJ, PJOM and PTM. PJOM was supported by a Royal Society Fellowship, NAS by the International Campus of Excellence of the Canary Islands, MJ by the Marine Alliance for Science and Technology for Scotland and AF partly by project CETOBAPH (grant number CGL2009-1311218).Predators make foraging decisions based upon sensory information about resource availability, but little is known about how large, air-breathing predators collect and use such information to maximize energy returns when foraging in the deep sea. Here, we used archival tags to study how echolocating sperm whales (Physeter macrocephalus) use their long-range sensory capabilities to guide foraging in a deep-water habitat consisting of multiple, depth-segregated prey layers. Sperm whales employ a directed search behaviour by modulating their overall sonar sampling with the intention to exploit a particular prey layer. They forage opportunistically during some descents while actively adjusting their acoustic gaze to sequentially track different prey layers. While foraging within patches, sperm whales adjust their clicking rate both to search new water volumes as they turn and to match the prey distribution. This strategy increases information flow and suggests that sperm whales can perform auditory stream segregation of multiple targets when echolocating. Such flexibility in sampling tactics in concert with long-range sensing capabilities apparently allow sperm whales to efficiently locate and access prey resources in vast, heterogeneous, deep water habitats.PostprintPeer reviewe

Anti-aging potential of extracts from Washingtonia filifera seeds

The aim of this study was to test the inhibitory effect of fruit extracts from Washingtonia filifera on skin aging-related enzymes. The pulp extracts did not exert a significant enzyme inhibition while seed extracts from W. filifera exhibit anti-elastase, anti-collagenase, and anti-tyrosinase activities. Tyrosinase was mildly inhibited while a stronger effect was observed with respect to elastase and collagenase inhibition. Alcoholic extracts provided better results than aqueous extracts. Among them, methanol extracts showed the prominent enzyme inhibitory activities being IC50 value for elastase and collagenase comparable and even better than the reference compound. The inhibition mode of the most active extracts was investigated by Lineweaver-Burk plot analysis. Seed extracts from W. filifera were also investigated for their photo-protective effect by Mansur equation and the antioxidant activity of W. filifera extract was evaluated in oxidative-stressed cells. To evaluate the safety of the extract, the effect on cell viability of human keratinocytes cells was analyzed. Methanol extract presented the best photo-protective effect and exerted an antioxidant activity in a cellular system with no cytotoxic effect. The overall results demonstrate that W. filifera extracts are promising sources of bioactive compounds that could be used in cosmetic and pharmaceutical preparation

Assessment of the structural and functional characteristics of human mesenchymal stem cells associated with a prolonged exposure of morphine

The discovery of the expression of opioid receptors in the skin and their role in orchestrating the process of tissue repair gave rise to questions regarding the potential effects of clinical morphine treatment in wound healing. Although short term treatment was reported to improve tissue regeneration, in vivo chronic administration was associated to an impairment of the physiological healing process and systemic fibrosis. Human mesenchymal stem cells (hMSCs) play a fundamental role in tissue regeneration. In this regard, acute morphine exposition was recently reported to impact negatively on the functional characteristics of hMSCs, but little is currently known about its long-term effects. To determine how a prolonged treatment could impair their functional characteristics, we exposed hMSCs to increasing morphine concentrations respectively for nine and eighteen days, evaluating in particular the fibrogenic potential exerted by the long-term exposition. Our results showed a time dependent cell viability decline, and conditions compatible with a cellular senescent state. Ultrastructural and protein expression analysis were indicative of increased autophagy, suggesting a relation to a detoxification activity. In addition, the enhanced transcription observed for the genes involved in the synthesis and regulation of type I collagen suggested the possibility that a prolonged morphine treatment might exert its fibrotic potential risk, even involving the hMSCs

Meiofauna metabarcoding in Lima estuary (Portugal) suggests high taxon replacement within a background of network stability

Meiofauna organisms play an important role in ecological and sedimentary processes in estuarine ecosystems. Recently, the application of environmental DNA (eDNA) for investigating meiofauna in different environments, improved the accessibility to its diversity and composition in a scale, frequency and depth previously unattainable. Nevertheless, little attention has been given to the description of baseline patterns of coupled spatial and temporal dynamics of meiobenthic communities. In an earlier study conducted in Lima estuary (NW Portugal), using eDNA metabarcoding of sediment samples, high levels of meiofauna Operational Taxonomic Units (OTUs) turnover were recorded, between sampling points only a few metres apart, and among sampling stations along the estuary. In order to verify the consistency of these patterns, in the current study we re-assessed Lima estuary's meiofauna communities approximately 1 year after, applying the same methodological approach (targeting segments of the COI and 18S rRNA genes), and expanding HTS-data analyses through the use of association networks. A high degree of spatial turnover was found both within and between sampling stations and this was consistent for both markers and years. As a consequence, most of the beta-diversity was accounted by OTU replacement with only a minor contribution from OTU richness. Despite the high levels of OTU replacement, relatively stable network properties were found in meiofaunal communities, irrespective of the sampled year. Network properties appear to shift sharply from the downstream/high salinity area of the estuary to the mesohaline medium-upstream areas, suggesting high resilience and redundancy of meiofaunal communities along the estuarine gradient. The recognition of meiofauna's networks features may improve the understanding of the ecology and dynamics of these communities that apparently hold large portions of variable elements, thereby making difficult their analyses solely based on the OTU/species composition.This study was funded by the project "The NextSea: Next generation monitoring of coastal ecosystems in a scenario of global change'' (operacao NORTE-01-0145-FEDER-000032), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). Maria Fais and Sofia Duarte were supported, respectively by a Ph.D. (SFRH/BD/113547/2015) and a post-doc fellowship (SFRH/BPD/109842/2015) from FCT. The authors would like to thank Prof. Jesus Troncoso (University of Vigo) and Prof. Pedro Gomes (University of Minho) for their availability and hospitality for the lab processing; Dr. Bruno Sampieri and Barbara Leite (University of Minho) for the great support during the implementation of the practical stage of the research. The authors would like also to thank the anonymous reviewers for critically reading the manuscript and suggesting substantial improvements

Tyrosinase Inhibitor Activity of Coumarin-Resveratrol Hybrids

In the present work we report on the contribution of the coumarin moiety to tyrosinase inhibition. Coumarin-resveratrol hybrids 1-8 have been resynthesized to investigate the structure-activity relationships and the IC50 values of these compounds were measured. The results showed that these compounds exhibited tyrosinase inhibitory activity. Compound 3-(3’,4’,5’-trihydroxyphenyl)-6,8-dihydroxycoumarin (8) is the most potent compound (0.27 mM), more so than umbelliferone (0.42 mM), used as reference compound. The kinetic studies revealed that compound 8 caused non-competitive tyrosinase inhibition