Marine 5-thiohistidines as protective molecules from skin damage

Introduction Marine environment is a great source of bioactive molecules, whose biological properties and applications are often used especially to prevent skin diseases and aging caused by UVA­exposure. Ovothiols are methyl­5­thiohistidines from marine invertebrates, bacteria, and microalgae, which protect cells from environmental stressors. Recently, we have shown that, ovothiol, isolated from sea urchin eggs, exerts anti­inflammatory and antioxidant activities on human endothelial cells, and exhibits antifibrotic effect in an in vivo model of liver fibrosis.info:eu-repo/semantics/publishedVersio

Natural Sulfur-Containing Compounds: An Alternative Therapeutic Strategy against Liver Fibrosis

Liver fibrosis is a pathophysiologic process involving the accumulation of extracellular matrix proteins as collagen deposition. Advanced liver fibrosis can evolve in cirrhosis, portal hypertension and often requires liver transplantation. At the cellular level, hepatic fibrosis involves the activation of hepatic stellate cells and their transdifferentiation into myofibroblasts. Numerous pro-fibrogenic mediators including the transforming growth factor-β1, the platelet-derived growth factor, endothelin-1, toll-like receptor 4, and reactive oxygen species are key players in this process. Knowledge of the cellular and molecular mechanisms underlying hepatic fibrosis development need to be extended to find novel therapeutic strategies. Antifibrotic therapies aim to inhibit the accumulation of fibrogenic cells and/or prevent the deposition of extracellular matrix proteins. Natural products from terrestrial and marine sources, including sulfur-containing compounds, exhibit promising activities for the treatment of fibrotic pathology. Although many therapeutic interventions are effective in experimental models of liver fibrosis, their efficacy and safety in humans are largely unknown. This review aims to provide a reference collection on experimentally tested natural anti-fibrotic compounds, with particular attention on sulfur-containing molecules. Their chemical structure, sources, mode of action, molecular targets, and pharmacological activity in the treatment of liver disease will be discussed

Antioxidant and immune response of the sea urchin Paracentrotus lividus to different re-suspension patterns of highly polluted marine sediments

Marine pollution due to disused industrial activities is a major threat to ecosystems and human health, for example through the effects of re-suspension of toxic substances that are present in contaminated sediments. Here, we examined the effects of different re-suspension patterns of polluted sediments from the site of national interest Bagnoli-Coroglio, on the immune system of the sea urchin Paracentrotus lividus. An indoor experiment was set up exposing sea urchins for 34 days to such sediments and evaluating the effects of two patterns of water turbulence, mimicking natural storms at sea. One group of animals experienced an “aggregated” pattern of turbulence, consisting in two events, each lasting 2 days, separated by only 3 calm days, while a second group experienced two events of turbulence separated by 17 calm days (spaced pattern). At different times from the beginning of the experiment, coelomic fluid was collected from the animals and immune cells were examined for cell count and morphology, oxidative stress variables, and expression of genes involved in metal detoxification, stress response and inflammation. Our results highlighted that the aggregated pattern of turbulence was more noxious for sea urchins. Indeed, their immune system was altered, over the exposure time, as indicated by the increase of red amoebocytes number. Moreover, despite of an increase of the antioxidant power, animals from this group displayed a very significant ROS over-production at the end of the experiment. Conversely, animals in the spaced condition activated a different immune response, mainly having phagocytes as actors, and were able to partially recover from the received stress at the end of the experiment. No changes in the expression of genes related to antioxidant and anti-inflammatory responses were observed in both groups. By contrast, a down-regulation of various metallothioneins (4, 6, 7 and 8) in the group subjected to aggregated pattern was observed, while metallothionein 8 was up-regulated in the animals from the group exposed to the spaced pattern of turbulence. This work provides the first evidence of how sea urchins can respond to different re-suspension patterns of polluted sediments by modulating their immune system functions. The present data are relevant in relation to the possible environmental restoration of the study site, whose priorities include the assessment of the effects of marine pollution on local organisms, among which P. lividus represents a key benthic species

Insights into the light response of skeletonema marinoi: Involvement of ovothiol

Diatoms are one of the most widespread groups of microalgae on Earth. They possess extraordinary metabolic capabilities, including a great ability to adapt to different light conditions. Recently, we have discovered that the diatom Skeletonema marinoi produces the natural antioxidant ovothiol B, until then identified only in clams. In this study, we investigated the light-dependent modulation of ovothiol biosynthesis in S. marinoi. Diatoms were exposed to different light conditions, ranging from prolonged darkness to low or high light, also differing in the velocity of intensity increase (sinusoidal versus square-wave distribution). The expression of the gene encoding the key ovothiol biosynthetic enzyme, ovoA, was upregulated by high sinusoidal light mimicking natural conditions. Under this situation higher levels of reactive oxygen species and nitric oxide as well as ovothiol and glutathione increase were detected. No ovoA modulation was observed under prolonged darkness nor low sinusoidal light. Unnatural conditions such as continuous square-wave light induced a very high oxidative stress leading to a drop in cell growth, without enhancing ovoA gene expression. Only one of the inducible forms of nitric oxide synthase, nos2, was upregulated by light with consequent production of NO under sinusoidal light and darkness conditions. Our data suggest that ovothiol biosynthesis is triggered by a combined light stress caused by natural distribution and increased photon flux density, with no influence from the daily light dose. These results open new perspectives for the biotechnological production of ovothiols, which are receiving a great interest for their biological activities in human model systems

A king and vassals' tale: Molecular signatures of clonal integration in Posidonia oceanica under chronic light shortage

Under unfavourable conditions, clonal plants benefit from physiological integration among ramets, sharing resources and information. Clonal integration can buffer against environmental changes and lets the plant clone work as a ‘macro’ organism. Molecular signals that regulate this phenomenon are completely unknown in marine plants. Here we present a first comprehensive study providing insights into the metabolic role of different types of ramets (i.e. apical vs. vertical) in the foundation species Posidonia oceanica. Plants were exposed to 80% diminishing irradiance level (LL) in a controlled mesocosm system. Subsequent multiscale variations in whole transcriptome expression, global DNA methylation level, photo-physiology, morphology and fitness-related traits, were explored at different exposure times. We tested the hypothesis that vertical shoots (the ‘vassals’) can provide vital resources to apical shoots (the ‘kings’) under energy shortage, thus safeguarding the whole clone survival. Whole transcriptome analysis of leaves and shoot-apical meristems (SAMs) emphasized signatures of molecular integration among ramets, which strongly correlated with higher organization-level responses. In both shoots types, the exposure to LL resulted in a growth slowdown throughout the experiment, which started from immediate signals in SAMs. In apical shoots, this was linked to an acclimative response, where they were suffering a mild stress condition, while in vertical ones it fell in a more severe stress response. Yet, they suffered from sugar starvation and showed a clear cellular stress response in terms of protein refolding and DNA repair mechanisms. Several epigenetic mechanisms modulated the observed gene-expression patterns and the cross-talk between DNA methylation and the cellular energetic status appeared to regulate shoot metabolism under LL. Synthesis. Our results demonstrate a high level of specialization of integrated ramets within seagrass clones and a ‘division of labour’ under adverse conditions. Vertical shoots appear to do ‘most of the job’ especially in terms of resource providing, whereas activated functions in apical shoots were restricted to few important processes, according to an ‘energy-saving’ strategy. The response of vertical shoots could be seen as a ‘sacrificing response’ allowing the survival of ‘the king’ that is key for ensuring propagation and population maintenance, and for the colonization of new environments

Ovothiol ensures the correct developmental programme of the sea urchin Paracentrotus lividus embryo

Ovothiols are π-methyl-5-thiohistidines produced in great amounts in sea urchin eggs, where they can act as protective agents against the oxidative burst at fertilization and environmental stressors during development. Here we examined the biological relevance of ovothiol during the embryogenesis of the sea urchin Paracentrotus lividus by assessing the localization of the key biosynthetic enzyme OvoA, both at transcript and protein level, and perturbing its protein translation by morpholino antisense oligonucleotide-mediated knockdown experiments. In addition, we explored the possible involvement of ovothiol in the inflammatory response by assessing ovoA gene expression and protein localization following exposure to bacterial lipopolysaccharide. The results of the present study suggest that ovothiol may be a key regulator of cell proliferation in early developing embryos. Moreover, the localization of OvoA in key larval cells and tissues, in control and inflammatory conditions, suggests that ovothiol may ensure larval skeleton formation and mediate inflammatory processes triggered by bacterial infection. This work significantly contributes to the understanding of the biological function of ovothiols in marine organisms, and may provide new inspiration for the identification of the biological activities of ovothiols in humans, considering the pharmacological potential of these molecules

Ligation of the intersphincteric fistula tract (LIFT) to treat anal fistula: early results from a prospective observational study

Ligation of the intersphincteric tract (LIFT), a novel sphincter-saving technique, has been recently described with promising results. Literature data are still scant. In this prospective observational study, we present our experience with this technique

Protocol for the unclassified primary antibody deficiency (unPAD) study:Characterization and classification of patients using the ESID online registry

BACKGROUND: Primary antibody deficiencies (PADs) without an identified monogenetic origin form the largest and most heterogeneous group of primary immunodeficiencies. These patients often remain undiagnosed for years and many present to medical attention in adulthood after several infections risking structural complications. Not much is known about their treatment, comorbidities, or prognosis, nor whether the various immunological forms (decreased total IgG, IgG subclass(es), IgM, IgA, specific antibody responses, alone or in combination(s)) should be considered as separate, clearly definable subgroups. The unclassified primary antibody deficiency (unPAD) study aims to describe in detail all PAD patients without an identified specific monogenetic defect regarding their demographical, clinical, and immunological characteristics at presentation and during follow-up. In constructing these patterns, the unPAD study aims to reduce the number of missed and unidentified PAD patients in the future. In addition, this study will focus on subclassifying unPAD to support the identification of patients at higher risk for infection or immune dysregulation related complications, enabling the development of personalized follow-up and treatment plans. METHODS AND ANALYSIS: We present a protocol for a multicenter observational cohort study using the ESID online Registry. Patients of all ages who have given informed consent for participation in the ESID online Registry and fulfill the ESID Clinical Working Definitions for ‘unclassified antibody deficiency’, ‘deficiency of specific IgG’, ‘IgA with IgG subclass deficiency’, ‘isolated IgG subclass deficiency’, ‘selective IgM deficiency’, ‘selective IgA deficiency’ or ‘common variable immunodeficiency’ will be included. For all patients, basic characteristics can be registered at first registration and yearly thereafter in level 1 forms. Detailed characteristics of the patients can be registered in level 2 forms. Consecutive follow-up forms can be added indefinitely. To ensure the quality of the collected data, all data will be fully monitored before they are exported from the ESID online Registry for analysis. Outcomes will be the clinical and immunological characteristics of unPAD at presentation and during follow-up. Subgroup analyses will be made based on demographical, clinical and immunological characteristics

Non cross-linked equine collagen (Salvecoll-E gel) for treatment of complex ano-rectal fistula

Summary: Background: Fistula-in-ano is one of the most commonly presenting anorectal diseases. Sphincter sparing treatment options should be considered in patients with complex fistulas. Salvecoll-E gel is a native collagen deantigenated and purified, non-cross-linked equine dermal extract, with an amino acid composition identical to human collagen. Methods: The multicentric trial study was a prospective, single-arm observational clinical study with the objective to assess the efficacy of Salvecoll-E gel for anal fistula repair in 70 patients. All patients had undergone preliminary surgical treatment consisting of positioning of a draining loosing seton that was maintained for a period of 4–6 weeks. After seton removal, a gentle debridement and washing of the fistula track was performed. The scar tissue was removed from the internal orifice. Internal opening was covered by a side-to side mucosal suture. Salvecoll-E was injected through the external opening into the fistula track, the external opening it has been opened. Results: Twelve months after surgery, 55 patients demonstrated a clinically healed fistula (78,5%), 15 patients have a recurrence (21,5%). Most of the recurrences were observed in the first 6 months of treatment (13/15, 86.6%). We don't observe any worsening in CCF score. The results obtained at 1 year certainly seem satisfactory and in line with the best results published in literature using mini-invasive techniques. Conclusion: Salvecoll-E gel is a promising non-invasive technique for conservative treatment of anal fistulas, it's well tolerated by the patients and, in case of recurrence, reinjection or all other known techniques are feasible. Keywords: Complex ano-rectal fistula, Non cutting technique, Mini-invasive treatmen