Understanding the connection between platelet-activating factor, a UV-induced lipid mediator of inflammation, immune suppression and skin cancer.

none2siLipid mediators of inflammation play important roles in several diseases including skin cancer, the most prevalent type of cancer found in the industrialized world. Ultraviolet (UV) radiation is a complete carcinogen and is the primary cause of skin cancer. UV radiation is also a potent immunosuppressive agent, and UV-induced immunosuppression is a well-known risk factor for skin cancer induction. An essential mediator in this process is the glyercophosphocholine 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine commonly referred to as platelet-activating factor (PAF). PAF is produced by keratinocytes in response to diverse stimuli and exerts its biological effects by binding to a single specific G-protein-coupled receptor (PAF-R) expressed on a variety of cells. This review will attempt to describe how this lipid mediator is involved in transmitting the immunosuppressive signal from the skin to the immune system, starting from its production by keratinocytes, to its role in activating mast cell migration in vivo, and to the mechanisms involved that ultimately lead to immune suppression. Recent findings related to its role in regulating DNA repair and activating epigenetic mechanisms, further pinpoint the importance of this bioactive lipid, which may serve as a critical molecular mediator that links the environment (UVB radiation) to the immune system and the epigenome.openDamiani, E; Ullrich, S.E.Damiani, Elisabetta; Ullrich, S. E

From Sea to Skin: Is There a Future for Natural Photoprotectants?

In the last few decades, the thinning of the ozone layer due to increased atmospheric pollution has exacerbated the negative effects of excessive exposure to solar ultraviolet radiation (UVR), and skin cancer has become a major public health concern. In order to prevent skin damage, public health advice mainly focuses on the use of sunscreens, along with wearing protective clothing and avoiding sun exposure during peak hours. Sunscreens present on the market are topical formulations that contain a number of different synthetic, organic, and inorganic UVR filters with different absorbance profiles, which, when combined, provide broad UVR spectrum protection. However, increased evidence suggests that some of these compounds cause subtle damage to marine ecosystems. One alternative may be the use of natural products that are produced in a wide range of marine species and are mainly thought to act as a defense against UVR-mediated damage. However, their potential for human photoprotection is largely under-investigated. In this review, attention has been placed on the molecular strategies adopted by marine organisms to counteract UVR-induced negative effects and we provide a broad portrayal of the recent literature concerning marine-derived natural products having potential as natural sunscreens/photoprotectants for human skin. Their chemical structure, UVR absorption properties, and their pleiotropic role as bioactive molecules are discussed. Most studies strongly suggest that these natural products could be promising for use in biocompatible sunscreens and may represent an alternative eco-friendly approach to protect humans against UV-induced skin damage

Repurposing of Idebenone as a potential anticancer agent

Funding. E.D. was funded by an internal research grant from the Polytechnic University of the Marche provided by MIUR (Italian Ministry of University and Research). Funding for FACS experiments was provided by grant code no. RO10014-13 from the Cell, Developmental and Cancer Biology Research Programme, University of Aberdeen.Peer reviewedPostprin

How reliable are in vitro IC50 values? Values vary with cytotoxicity assays in human glioblastoma cells

Funding E.D. was funded by an internal research grant from the Polytechnic University of the Marche provided by MIUR (Italian Ministry of University and Research).Peer reviewedPostprin

Valorisation of Crocus sativus flower parts for herbal infusions: impact of brewing conditions on phenolic profiling, antioxidant capacity and sensory traits

Saffron production from Crocus sativus flowers produces large amounts of by-products that may represent an excellent source of polyphenols. The aim of this work was to evaluate infusions originating from different brewing processes and from different saffron flower portions, in terms of both functional and sensory traits. For this aim, total polyphenols and total flavonoids, in vitro antioxidant assays and an untargeted phenolic profiling were applied. In general, tepals showed higher polyphenol and flavonoid content than stamen infusions, and their bioactive content depended more on brewing temperature than brewing time. These findings were consistent with both antioxidant capacity and phenolic profiling. Multivariate statistics highlighted polyphenols discriminating ‘boiled’ vs. ‘cold’ infusions, being mainly flavonoids, phenolic acids and the alkylphenol 5-pentadecylresorcinol (showing a strong down-accumulation at the higher brewing temperatures). Positive correlations could be highlighted between anthocyanins, flavones, flavonols and lignans, and the in vitro antioxidant assays. In general, cold brewing was successful in extracting phenolic compounds and provided better sensory properties, thus indicating that this may represent a valuable strategy to develop saffron-based functional beverages with better consumers' acceptability

Influence of Light Stress on the Accumulation of Xanthophylls and Lipids in Haematococcus pluvialis CCALA 1081 Grown under Autotrophic or Mixotrophic Conditions

The influence of light stress and trophic environmental conditions on the production of astaxanthin, other xanthophylls and lipids from an Argentinian strain of Haematococcus pluvialis was investigated. Microalgae cultures were incubated for two weeks in autotrophic or mixotrophic conditions (with sodium acetate in the culture medium) and subjected to two different light stresses. HPLC analyses showed that: 1) regardless of the growth conditions, microalgal cells accumulated most of the astaxanthin (about 90%) in esterified form; 2) maximal increase of astaxanthin level was observed in the culture grown in autotrophic conditions subjected to moderate light stress (90 μmol photons m-2 s-1), while the same light regime in mixotrophic conditions led to a lower increase (only 25.8 fold); 3) in the case of high light stress (350 μmol photons m-2 s-1), the adaptive response of microalgae also led to a significant increase in the amount of astaxanthin both in autotrophic (22 fold increase) and in mixotrophic (16 fold increase) conditions; 4) an inverse correlation (R2 = 0.977) exists between the amount of lipids and that of astaxanthin accumulated by Haematococcus grown under different growth conditions; 5) lutein was found to be the most accumulated pigment in microalgae not subjected to light stress.Fil: Doria, Enrico. University of Pavia. Department of Biology and Biotechnology; ItaliaFil: Temporiti, Marta Elisabetta E.. University of Pavia. Department of Biology and Biotechnology; ItaliaFil: Damiani, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Popovich, Cecilia Angelines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Leonardi, Patricia Ines. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; ArgentinaFil: Nielsen, Erik. University of Pavia. Department of Biology and Biotechnology; Itali

Therapeutic Efficacy of the Novel Stimuli-Sensitive Nano-Ferritins Containing Doxorubicin in a Head and Neck Cancer Model

Doxorubicin is employed alone or in combination for the treatment of several hematological and solid malignancies; despite its efficacy, there are associated cardiotoxicity limits both in its application in patients with heart disease risk factors and also in its long-term use. HFt-MP-PAS40 is a genetically engineered human ferritin heavy chain (HFt)-based construct able to efficiently entrap and deliver doxorubicin to cancer cells. HF-MP-PAS contains a short motif sequence (defined as MP) responsive to proteolytic cleavage by tumor matrix metalloproteases (MMPs), located between each HFt subunit and a masking polypeptide sequence rich in proline (P), alanine (A), and serine (S) residues (PAS). This carrier displayed excellent therapeutic efficacy in a xenogenic pancreatic cancer model in vivo, leading to a significant increase in overall animal survival in treated mice. Herein, we describe the HFt-MP-PAS40-Dox efficacy against squamous cell carcinomas of the head and neck (HNSCC) with the goal of validating the application of our nano-drug for the treatment of different solid tumors. In addition, a tolerability study in healthy mice was also performed. The results indicate that HFt-MP-PAS40-Dox produced increased anti-tumor effects both in vitro and in vivo in comparison to the free drug in several HNSCC cell lines. In the acute toxicity studies, the maximum tolerated dose (MTD) of HFt-MP-PAS40-Dox was about 3.5 higher than the free drug: 25 mg/kg versus 7 mg/kg doxorubicin equivalents. Importantly, evaluation of heart tissues provided evidence that doxorubicin is less cardio-toxic when encapsulated inside the ferritin carrier. In conclusion, HFt-MP-PAS40-Dox may be administered safely at higher doses compared with the free drug, resulting in superior efficacy to control HNSCC malignancies

Sunscreens Cause Coral Bleaching by Promoting Viral Infections

Background: Coral bleaching (i.e., the release of coral symbiotic zooxanthellae) has negative impacts on biodiversity and functioning of reef ecosystems and their production of goods and services. This increasing world-wide phenomenon is associated with temperature anomalies, high irradiance, pollution, and bacterial diseases. Recently, it has been demonstrated that personal can products, including sunscreens, have an impact on aquatic organisms similar to that of other contaminants. Objectives: Our goal was to evaluate the potential impact of sunscreen ingredients on hard corals and their symbiotic algae. Methods: In situ and laboratory experiments were conducted in several tropical regions (the Atlantic, Indian, and Pacific Oceans, and the Red Sea) by supplementing coral branches with aliquots of sunscreens and common ultraviolet filters contained in sunscreen formula. Zooxanthellae were checked for viral infection by epifluorescence and transmission electron microscopy analyses. Results: Sunscreens cause the rapid and complete bleaching of hard corals, even at extremely low concentrations. The effect of sunscreens is due to organic ultraviolet filters, which are able to induce the lyric viral cycle in symbiotic zooxanthellae with latent infections. Conclusions: We conclude that sunscreens, by promoting viral infection, potentially play an important role in coral bleaching in areas prone to high levels of recreational use by humans

The serological prevalence of SARS-CoV-2 infection in patients with chronic myeloid leukemia is similar to that in the general population

Patients with hematological malignancies are at an increased risk of SARS-CoV-2 disease (COVID-19) and adverse outcome. However, a low mortality rate has been reported in patients with chronic myeloid leukemia (CML). Preclinical evidence suggests that tyrosine kinase inhibitors (TKIs) may have a protective role against severe COVID-19