Search

International audience; Sea urchins are emblematic models in developmental biology and display several characteristics that set them apart from other deuterostomes. To uncover the genomic cues that may underlie these specificities, we generated a chromosome-scale genome assembly for the sea urchin Paracentrotus lividus and an extensive gene expression and epigenetic profiles of its embryonic development. We found that, unlike vertebrates, sea urchins retained ancestral chromosomal linkages but underwent very fast intrachromosomal gene order mixing. We identified a burst of gene duplication in the echinoid lineage and showed that some of these expanded genes have been recruited in novel structures (water vascular system, Aristotle’s lantern, and skeletogenic micromere lineage). Finally, we identified gene-regulatory modules conserved between sea urchins and chordates. Our results suggest that gene-regulatory networks controlling development can be conserved despite extensive gene order rearrangement.

Obesity and related metabolic dysfunctions are associated with neurodegenerative diseases, such as Alzheimer’s disease. Aphanizomenon flos-aquae (AFA) is a cyanobacterium considered a suitable supplement for its nutritional profile and beneficial properties. The potential neuroprotective effect of an AFA extract, commercialized as KlamExtra®, including the two AFA extracts Klamin® and AphaMax®, in High-Fat Diet (HFD)-fed mice was explored. Three groups of mice were provided with a standard diet (Lean), HFD or HFD supplemented with AFA extract (HFD + AFA) for 28 weeks. Metabolic parameters, brain insulin resistance, expression of apoptosis biomarkers, modulation of astrocytes and microglia activation markers, and Aβ deposition were analyzed and compared in the brains of different groups. AFA extract treatment attenuated HFD-induced neurodegeneration by reducing insulin resistance and loss of neurons. AFA supplementation improved the expression of synaptic proteins and reduced the HFD-induced astrocytes and microglia activation, and Aβ plaques accumulation. Together, these outcomes indicate that regular intake of AFA extract could benefit the metabolic and neuronal dysfunction caused by HFD, decreasing neuroinflammation and promoting Aβ plaques clearance.

The subsurface is among Earth’s largest biomes, but the extent to which microbial communities vary across tectonic plate boundaries or interact with subduction-scale geological processes remains unknown. Here we compare bacterial community composition with deep-subsurface geochemistry from 21 hot springs across the Costa Rican convergent margin. We find that cation and anion compositions of the springs reflect the dip angle and position of the underlying tectonic structure and also correlate with the bacterial community. Co-occurring microbial cliques related to cultured chemolithoautotrophs that use the reverse tricarboxylic acid cycle (rTCA) as well as abundances of metagenomic rTCA genes correlate with concentrations of slab-volatilized carbon. This, combined with carbon isotope evidence, suggests that fixation of slab-derived CO2 into biomass may support a chemolithoautotrophy-based subsurface ecosystem. We calculate that this forearc subsurface biosphere could sequester 1.4 × 109 to 1.4 × 1010 mol of carbon per year, which would decrease estimates of the total carbon delivered to the mantle by 2 to 22%. Based on the observed correlations, we suggest that distribution and composition of the subsurface bacterial community are probably affected by deep tectonic processes across the Costa Rican convergent margin and that, by sequestering carbon volatilized during subduction, these chemolithoautotrophic communities could in turn impact the geosphere. The subsurface biosphere across a convergent margin may reflect tectonic processes and reduce carbon transfer to the mantle, according to bacterial and geochemical correlations from hot springs across the Costa Rican margin.

Alzheimer disease (AD) is a multifactorial and age-dependent neurodegenerative disorder, whose pathogenesis, classically associated with the formation of senile plaques and neurofibrillary tangles, is also dependent on oxidative stress and neuroinflammation chronicization. Currently, the standard symptomatic therapy, based on acetylcholinesterase inhibitors, showed a limited therapeutic potential, whereas disease-modifying treatment strategies are still under extensive research. Previous studies have demonstrated that Oxotremorine-M (Oxo), a non-selective muscarinic acetylcholine receptors agonist, exerts neurotrophic functions in primary neurons, and modulates oxidative stress and neuroinflammation phenomena in rat brain. In the light of these findings, in this study, we aimed to investigate the neuroprotective effects of Oxo treatment in an in vitro model of AD, represented by differentiated SH-SY5Y neuroblastoma cells exposed to Aβ1-42 peptide. The results demonstrated that Oxo treatment enhances cell survival, increases neurite length, and counteracts DNA fragmentation induced by Aβ1-42 peptide. The same treatment was also able to block oxidative stress and mitochondria morphological/functional impairment associated with Aβ1-42 cell exposure. Overall, these results suggest that Oxo, by modulating cholinergic neurotransmission, survival, oxidative stress response, and mitochondria functionality, may represent a novel multi-target drug able to achieve a therapeutic synergy in AD. Graphical Abstract Illustration of the main pathological hallmarks and mechanisms underlying AD pathogenesis, including neurodegeneration and oxidative stress, efficiently counteracted by treatment with Oxo, which may represent a promising therapeutic molecule. Created with BioRender.com under academic license.

Accumulating evidences indicate that inflammatory and oxidative stress play an essential role in the pathogenesis and progression of inflammatory bowel disease (IBD). In IBD the excessive production of reactive oxygen species (ROS) and nitrogen metabolites contribute to tissue injury and could have also a profound impact on gut functions, including motility. We characterised the inflammatory and oxidative condition and the impact on colon motility in an experimental rat model of colitis, the 2, 4-dinitrobenzene sulfonic acid (DNBS)- induced colitis, and we evaluated if oral treatment with a nat- ural extract of Aphanizomenon flos-aquae (AFA) AphaMax®, containing concentrated quantity of AFA-phycocyanins(PCs), compound with a significantly higher antioxidant power than other PCs, can attenuate the inflammatory and oxidative stress and help to recover intestinal motor functionality. Inflamed preparations from DNBS induced colitis rats showed an increase of different inflammatory markers, as MPO activity, a biochemical index for neutrophil infiltration, an increase in the expression of pro inflammatory cytokines and in the levels of marker of oxidative stress as ROS and Nitrites. Inflamed preparations showed also macroscopic and microscopic tissue damages and a marked hypocontractility, as recorded invitro in colonic longitudinal muscle. AphaMax® downregulated in a dose-dependent manner colonic expression of cytokines, IL-1β, IL-6 and iNOS, the activity of MPO and improved anti-oxidant system, inhibiting also NF-κ B activation. The colon injury and the colonic contractility in inflamed tissues were also improved by AphaMax® treatment. Our data reveal that in DNBS-rat model an intense oxidative insult would contribute to tissue damage during chronic intestinal inflammation and that AphaMax®- treatment was able to modulate the redox status by scavenging ROS and reducing the severity of the colitis, contributing also to the recovery of colonic muscle functionality

The purpose of the present study was to evaluate the impact of long-term honey ingestion on metabolic disorders and neurodegeneration in mice fed a high-fat diet (HFD). Three groups of mice were fed with a standard diet (STD), HFD or HFD supplemented with honey (HFD-H) for 16 weeks. Biochemical, histological, Western blotting, RT-PCR and Profiler PCR array were performed to assess metabolic parameters, peripheral and central insulin resistance and neurodegeneration. Daily honey intake prevented the HFD-induced glucose dysmetabolism. In fact, it reduced plasma fasting glucose, insulin and leptin concentrations and increased adiponectin levels. It improved glucose tolerance, insulin sensitivity and HOMA index without affecting plasma lipid concentration. HFD mice showed a significantly higher number of apoptotic nuclei in the superficial and deep cerebral cortex, upregulation of Fas-L, Bim and P27 (neuronal pro-apoptotic markers) and downregulation of Bcl-2 and BDNF (anti-apoptotic factors) in comparison with STD- and HFD-H mice, providing evidence for honey neuroprotective effects. PCR-array analysis showed that long-term honey intake increased the expression of genes involved in insulin sensitivity and decreased genes involved in neuroinflammation or lipogenesis, suggesting improvement of central insulin resistance. The expressions of p-AKT and p-GSK3 in HFD-H mice, which were decreased and increased, respectively, in HFD mouse brain, index of central insulin resistance, were similar to STD animals supporting the ability of regular honey intake to protect brain neurons from insulin resistance. In conclusion, the present results provide evidence for the beneficial preventative impact of regular honey ingestion on neuronal damage caused by HFD.

Aims Nowadays continuous flow left ventricular assist devices (LVAD) have become a reality for patients with end-stage heart failure (HF) who are failing maximal medical treatment, both eligible or not for heart transplantation. LVADs have demonstrated to improve functional capacity and clinical outcomes, including breathing and activity tolerance, but the impact on patients quality of life (QoL) is still a vexed and open question. Moreover, the device implantation actually requires significant life style changes, high motivation and adherence to treatment, both for patients and their caregivers. Patients must learn to live with the device and to interface with the controller and batteries system, adjusting everyday life’s activities to the device presence. The purpose of our study is to evaluate how the implantation of HeartMate 3™ impact on patients-related QoL and clinical outcomes, compared with general population and other chronic diseases. Methods and results Eight patients (pts) with a diagnosis of end-stage HF were implanted with the HeartMate 3™ LVAD from May 2017 to October 2019 in the Cardiac Surgery Unit of Brotzu Hospital. During a follow-up visit (28.7 ± 11.9 months after surgery), the 7 pts presenting were assessed with two questionnaires, the SF-12 and EuroQoL-5D, in order to evaluate improvement of quality of life compared with clinical presentation. Afterwards we compared the average SF-12 total result with 28 controls from general population and with other important chronic diseases. The analysis of SF-12 questionnaires showed an average of 28.00 ± 8.98 (VN: 12–47) as total score, 11.7 ± 3.4 (VN: 6–20) as physical health component score and 16.2 ± 6.5 (VN: 6–27) as mental health component score. These findings, though within the range of ‘normality’, are closer to the lower scores and show the negative impact of LVAD in everyday patients-related quality of life. Comparing the NYHA functional class with these results, we found a statistically significant negative linear correlation for both total (−0.80, P = 0.03) and mental health component scores (−0.75, P = 0.049). Average total score of our pts significatively differs compared with 28 controls of general population (28.00 ± 8.98 vs. 38.64 ± 6.80, P = 0.014), as well as compared with other chronic diseases like Wilson’s disease (P Conclusions LVAD can improve clinical outcomes and functional capacity of carefully select pts with end-stage HF, but the complications encountered during mechanical support and the lifestyle changes required can affect negatively patients well-being. Many studies have shown that most patients experience significant improvement even in QoL’s perception but for others the device have a negative impact on many aspects of normal daily living as well as emotional, mental and social functioning. Our study confirms this conflicting results: physical related-quality of life improves after LVAD implantation but emotional and psychological distress may persist, especially during long-term support, as a result of complications, co-morbidities and personal’s attitudes, values and way of life.

Aims During the last decades left ventricular assist devices (LVAD) have assumed a central role in the management of patients with symptomatic end-stage heart failure (HF). The mortality rate and prognosis of these patients is poor, but the substantial progress in LVAD technologies has led to significant improvements in clinical outcomes. The third generation LVADs are small, centrifugal flow pumps, contained within the pericardium and based on full magnetic levitation, which allow to reduce the risks of pump thrombosis. The aim of our study is to evaluate the clinical outcomes and functional capacity of patients with end-stage HF before and after the implantation of a third generation LVAD, the HeartMate 3™. Methods and results We evaluated eight patients with end-stage HF, followed to Cardiology Unit of Brotzu Hospital in Cagliari and consecutively implanted with the HeartMate 3™ LVAD in the Cardiac Surgery Unit from 12 May 2017 to 24 October 2019. For each patient we collected socio-demographic and clinical features, as well as laboratory tests, therapy, echocardiographic and haemodynamics parameters and any complication. Most of our patients were male (87.5%), with mean age 65.6 ± 5.7 years and higher prevalence of cardiovascular risk factors, like smoke (87.5%), hypertension (62.5%) and hypercholesterolaemia (62.5%). The etiology of HF was mainly due to idiopatic dilated cardiomyopathy (62.5%) and ischaemic heart disease (25%); the only female patient had a history of iatrogenic dilated cardiomyopathy, post-chemo and radiotherapy. Before the implantation most of our patients experienced severe symptoms, recurrent decompensations resulting in NYHA class IV (50%) and III (37.5%); the 100% was inotrope dependant and needed short-term support devices like IABP (75%) and ECMO (25%); the 62.5% underwent mechanical ventilation. The patients had severe left ventricular (LV) dysfunction, with low LV ejection fraction (18.6 ± 1.8%), cardiac output (3.08 ± 1.2 l/min) and cardiac index (1.81 ± 0.83 l/min/m2) and increasing filling pressure (26.5 ± 9.7 mmHg), central venous pression (12.7 ± 5 mmHg) and pulmonary arteries resistance (3.81 ± 1 μW). We also found important LV structural changes, with a severe dilatation and increased volumes (EDV 140.62 ± 67.1 ml/m2; ESV 113.7 ± 55.3 ml/m2). Mild right ventricle dysfunction was present only in 50% of patients with normal diameters. We observed few complications, mainly driveline infections (42.8%) and only one case of in-hospital mortality due to multiple organ failure. The seven patients presenting at FU shown a significant improvement in everyday symptoms and functional capacity compared to pre-operative features (P = 0.029). We also found a mild improvement of systolic LV function compared to pre-operatory values, with increase of CO (3.58 ± 0.65 l/min vs. 3.08 ± 1.2) and EF (21.2 ± 9.4% vs. 18.71 ± 97) even though not statistically significant. Conclusions Our study confirms that patients with end-stage HF are mostly male, older, experience severe symptoms and require frequent hospitalizations. The survival rate reached the 87.5% and remained stable even three years after implantation. On the whole our study showed that LVADs can significally improve clinical outcomes and survival rates, confirming the role as treatment of choice for many patients with end-stage HF who cannot undergo heart transplantation, which still remains the gold standard. The complications related to LVAD were few, thanks to careful patients selection, showing a favourable risk benefit ratio.

Multifunctional bioplastics have been prepared by amorphous reassembly of cellulose, hemicelluloses (xylan), and hydrolyzed lignin. For this, the biopolymers were dissolved in a trifluoroacetic acid-trifluoroacetic anhydride mixture and blended in different percentages, simulating those found in natural woods. Free-standing and flexible films were obtained after the complete evaporation of the solvents. By varying xylan and hydrolyzed lignin contents, the physical properties were easily tuned. In particular, higher proportions of hydrolyzed lignin improved hydrodynamics, oxygen barrier, grease resistance, antioxidant, and antibacterial properties, whereas a higher xylan content was related to more ductile mechanical behavior, comparable to synthetic and bio-based polymers commonly used for packaging applications. In addition, these bioplastics showed high biodegradation rates in seawater. Such new polymeric materials are presented as alternatives to common man-made petroleum-based plastics used for food packaging.

Altered insulin signaling and insulin resistance are considered the link between Alzheimer's disease (AD) and metabolic syndrome. Here, by using an in vitro and an in vivo model, we investigated the relationship between these disorders focusing on neuronal mitochondrial dysfunction and mitophagy. In vitro Aβ insult induced the opening of mitochondrial permeability transition pore (mPTP), mitochondrial membrane potential (ΔΨm) loss, and apoptosis while insulin addition ameliorated these dysfunctions. The same alterations were detected in a 16 weeks of age mouse model of diet-induced obesity and insulin resistance. In addition, we detected an increase of fission related proteins and activation of mitophagy, proved by the rise of PINK1 and Parkin proteins. Nevertheless, in vitro, the increase of p62 and LC3 indicated an alteration in autophagy, while, in vivo decreased expression of p62 and increase of LC3 suggested removing of damaged mitochondria. Finally, in aged mice (28 and 48 weeks), the data indicated impairment of mitophagy and suggested the accumulation of damaged mitochondria. Taken together these outcomes indicate that alteration of the insulin pathway affects mitochondrial integrity, and effective mitophagy is age-dependent.

This abstract book contains the abstracts presented at the 93rd National Congress of the Italian Society of Experimental Biology; Palermo, Italy, 22-25 April 2021.

Ocean-warming and acidification jeopardize Antarctic marine species, adapted to cold and constant conditions and naturally exposed to high pro-oxidant pressures and cadmium (Cd) bioavailability. The aim of this study was to investigate if projected temperature increase and pH reduction may affect the accumulation and the effects of Cd in the rockcod Trematomus bernacchii. Organisms were exposed for 14 days to six scenarios, combining environmental or increased temperature (−1 °C, +1 °C) and control or reduced pH (8.05, 7.60), either with or without Cd (40 µg/L). Responses in liver and gills were analyzed at different levels, including mRNA and functional measurements of metallothioneins and of a wide battery of antioxidants, integrated with the evaluation of the total antioxidant capacity and onset of oxidative damages. In the gills, metallothioneins and mRNA of antioxidant genes (nrf2, keap1, cat, gpx1) increased after Cd exposure, but such effects were softened by warming and acidification. Antioxidants showed slighter variations at the enzymatic level, while Cd caused glutathione increase under warming and acidified scenarios. In the liver, due to higher basal antioxidant protection, limited effects were observed. Genotoxic damage increased under the combined stressors scenario. Overall results highlighted the modulation of the oxidative stress response to Cd by multiple stressors, suggesting the vulnerability of T. bernacchii under predicted ocean change scenarios.

Polyvinylpyrrolidone (commonly known as povidone or PVP) rapidly dissolves in water. This significantly hinders its use in sustained release formulations developed for the biomedical field. Electrospun fibers of PVP dissolve even faster due to larger surface to volume ratio. In this work, we propose a way to circumvent this problem by developing and using functional fibrous materials in hydrogel form. In particular, we demonstrate that ethanolic solutions of PVP containing two hydroxycinnamic acid derivatives, namely p-coumaric and ferulic acids could be electrospun into functional hydrogel fiber mats. After electrospinning, the formed composite mats were first thermally treated at 130 °C for 20 h and subsequently were immersed in aqueous media, where they turned into hydrogels. Thermal annealing did not degrade hydroxycinnamic acid derivatives, preserving their functionality. We propose these hydrogel fiber mats as potential wound dressings and to that end, in vitro tests showed up to 8 days of antioxidants’ release, and consequent protection of A549 epithelial cells against oxidative stresses. Biocompatibility tests using human red blood cells, A549 and HaCaT cell lines indicated no adverse effects. Model studies of mice skin burns induced by UV-B radiation showed that the hydrogel fiber dressings significantly reduced the levels of matrix metallopeptidase, (MMP-9), and glutathione peroxidase 1 (GPX-1), which are usually upregulated by reactive oxidative species on burnt skin. Finally, ex-vivo human skin investigations demonstrated skin regeneration and control of the inflammatory phase as indicated by low levels of pro-inflammatory cytokines (IL-6 and IL-8). Therefore, our outcomes indicate that the developed PVP-based fiber hydrogels, produced using a simple protocol, are promising candidates for active wound dressings.

Background: Aphanizomenon flos-aquae (AFA) is a unicellular cyanobacterium considered to be a &ldquo, superfood&rdquo, for its complete nutritional profile and beneficial properties. We investigated possible beneficial effects of an AFA extract, commercialized as AphaMax&reg, containing concentrated amount of phycocyanins and phytochrome, in 2,4 dinitrobenzensulfonic acid(DNBS)-induced colitis in rats. Methods: Effects of preventive oral treatment of AphaMax&reg, (20, 50 or 100 mg/kg/day) in colitic rats were assessed and then macroscopic and microscopic analyses were performed to evaluate the inflammation degree. Myeloperoxidase (MPO) activity and NF-&kappa, B, pro-inflammatory citockines, cycloxygenase-2 (COX-2), and inducible NOS (iNOS) levels of expression were determined, as Reactive Oxygen Species (ROS) and nitrite levels. Results: AphaMax&reg, treatment attenuated the severity of colitis ameliorating clinical signs. AphaMax&reg, reduced the histological colonic damage and decreased MPO activity, NF-&kappa, B activation, as well as iNOS and COX-2 expression. AphaMax&reg, treatment improved the altered immune response associated with colonic inflammation reducing IL-1&beta, IL-6 expression. Lastly, AphaMax&reg, reduced oxidative stress, decreasing ROS and nitrite levels. Conclusions: Preventive treatment with AphaMax&reg, attenuates the severity of the inflammation in DNBS colitis rats involving decrease of the NF-kB activation, reduction of iNOS and COX-2 expression, and inhibition of oxidative stress. Due its anti-inflammatory and antioxidant proprieties AphaMax&reg, could be a good candidate as a complementary drug in inflammatory bowel disease (IBD) treatment.

Background: Aphanizomenon flos-aquae (AFA) is a unicellular cyanobacterium considered to be a “superfood” for its complete nutritional profile and beneficial properties. We investigated possible beneficial effects of an AFA extract, commercialized as AphaMax®, containing concentrated amount of phycocyanins and phytochrome, in 2,4 dinitrobenzensulfonic acid(DNBS)-induced colitis in rats. Methods: Effects of preventive oral treatment of AphaMax® (20, 50 or 100 mg/kg/day) in colitic rats were assessed and then macroscopic and microscopic analyses were performed to evaluate the inflammation degree. Myeloperoxidase (MPO) activity and NF-κB, pro-inflammatory citockines, cycloxygenase-2 (COX-2), and inducible NOS (iNOS) levels of expression were determined, as Reactive Oxygen Species (ROS) and nitrite levels. Results: AphaMax® treatment attenuated the severity of colitis ameliorating clinical signs. AphaMax® reduced the histological colonic damage and decreased MPO activity, NF-κB activation, as well as iNOS and COX-2 expression. AphaMax® treatment improved the altered immune response associated with colonic inflammation reducing IL-1β, IL-6 expression. Lastly, AphaMax® reduced oxidative stress, decreasing ROS and nitrite levels. Conclusions: Preventive treatment with AphaMax® attenuates the severity of the inflammation in DNBS colitis rats involving decrease of the NF-kB activation, reduction of iNOS and COX-2 expression, and inhibition of oxidative stress. Due its anti-inflammatory and antioxidant proprieties AphaMax® could be a good candidate as a complementary drug in inflammatory bowel disease (IBD) treatment.

Background: Guanosine, a guanine-based purine, is an extracellular signaling molecule exerting anti-inflammatory and antioxidative effects in several in vivo and in vitro injury models. We aimed to investigate its protective effects on 2, 4-dinitrobenzene sulfonic acid (DNBS)-induced colitis in rat. Methods: Rats were divided into five groups and colitis was induced by intracolonic instillation of DNBS (15 mg/rat). Guanosine (4 or 8 mg/kg) was administered for 6 days i.p. starting the day of the colitis induction. Body weight loss, stool consistency, colon weight/length, histological analysis, myeloperoxidase activity (MPO) and pro-inflammatory cytokine levels were assessed. Immunoblotting of nuclear factor-κB (NF-κB) p65 protein levels and detection of oxidative and nitrosative stress markers were also performed. Results: Guanosine, in a dose-dependent manner, significantly ameliorated the severity of DNBS-induced colitis, reducing body weight loss and diarrhea incidence, preventing the DNBS-induced macroscopic and microscopic damage to the colonic mucosa, and the MPO increase. Guanosine treatment also lowered interleukin-1β, interleukin-6, and tumor necrosis factor-α mRNA levels. Importantly, guanosine in DNBS rats down-regulated the expression of NF-κB p65 and the levels of reactive oxygen species and nitrite. Conclusions: In conclusion, guanosine exerts beneficial effects in DNBS-induced colitis in rats, through modulation of colonic inflammation, downregulating of NFκB-mediated signaling.

Hypothesis Certain biobased polymers or natural compounds can be effectively used in superhydrophobic coating formulations to reduce environmental impact of fluorinated compounds and related bioaccumulation and toxicity problems. Many environmental concerns have thus far been raised in relation to toxicity of solvents and C8 fluorine chemicals. Elimination of these important elements from non-wettable coating formulations can jeopardize non-wetting performance significantly. However, intelligent and innovative approaches that introduce ecofriendly resins and compounds in superhydrophobic coating formulations without significantly altering self-cleaning superhydrophobicity are possible and being reported. Experiments Superhydrophobic coatings based on a biomass-derived bioresin polyfurfuryl alcohol (PFA) were prepared. The coatings were made by blending PFA resin with a C6 perfluorinated acrylic copolymer PFAC in solution and subsequent spray coating. Silica nanoparticles were also added in order to repel some common oils. Coating morphology, chemical and thermal properties, biocompatibility and bacterial adhesion properties were studied in detail. Findings Coatings having 50 wt% bioresin revealed equal water-repellency performance comapred to 100% PFAC-based coatings. Healthy cell growth was maintained on the coatings with no cell toxicity using human cell line, HeLa cells. Superhydrophobic coatings demonstrated very low bacterial adhesion to E. coli, S. aureus and Ps. aeruginosa indicating promising biofouling resistance. The coatings did not require any post thermal annealing. This would cause significant energy savings for large-scale adaptation.

Lemon pectin extracted along with water-soluble flavonoids and other phytochemicals from citrus industry’s waste lemon peel via hydrodynamic cavitation in water, directly at pre-industrial scale and further isolated via freeze drying, shows exceptionally high antioxidant and non-cytotoxic activity. Preliminary investigation indicates also significant antimicrobial activity. These findings open the route to the development of new nutraceutical and healthcare application of a versatile biopolymer endowed with new functionality, rapidly and conveniently obtained from an abundant by-product of the agrofood industry.

Obesity is a complex, chronic, and multifactorial condition characterized by abnormal fat accumulation in tissues and organs and inducing negative effects on human health. Alzheimer's disease is a progressive and irreversible neurodegenerative disease, associated with amyloid plaques and neurofibrillary tangles in the brain. The correlation between obesity and Alzheimer's disease has been discovered, but the molecules and molecular mechanisms linking these conditions are not yet fully elucidated. In this review, we focused on the most important processes linking the fat accumulation and the alterations of the brain structure and functions.

The aim of the present work is to demonstrate the practical importance of a multidisciplinary approach and weighted criteria to synthesize and integrate different typologies of data (or lines of evidence, LOEs), including chemical levels in marine sediments, their bioavailability to specific indicator species, ecotoxicological effects measured through subcellular biomarkers and batteries of bioassays, and potential impacts of pollution on local benthic communities. The area of Bagnoli (Gulf of Naples, Southern Italy) was selected as a model case-study, as it is a coastal area chronically impacted by massive industrial contamination (trace metals and hydrocarbons), and dismissed decades ago without any subsequent remediation or habitat restoration. The results of each LOE were elaborated to provide specific hazard indices before their overall integration in a weight of evidence (WOE) evaluation. Levels of some trace metals and PAHs revealed a severe contamination in the entire study area. Bioavailability of hydrocarbons was evident particularly for high molecular weight PAHs, which also caused significant variations of cellular biomarkers, such as cytochrome P450 metabolization in fish, lysosomal membrane destabilization in mussels, genotoxic effects both in fish and molluscs. The results of a battery of bioassays indicated less marked responses compared to those obtained from chemical and biomarkers analyses, with acute toxicity still present in sediments close to the source of contamination. The analysis of benthic assemblages showed limited evidence of impact in the whole area, indicating a good functioning of local ecosystems at chronic contamination. Overall, the results of this study confirm the need of combining chemical and biological data, the quantitative characterization of various typologies of hazard and the importance of assessing an integrated environmental WOE risk, to orientate specific and scientifically-supported management options in industrialized areas.

In 2017, fluid and gas samples were collected across the Costa Rican Arc. He and Ne isotopes, C isotopes as well as total organic and inorganic carbon concentrations were measured. The samples (n = 24) from 2017 are accompanied by (n = 17) samples collected in 2008, 2010 and 2012. He-isotopes ranged from arc-like (6.8 RA) to crustal (0.5 RA). Measured dissolved inorganic carbon (DIC) δ13CVPDB values varied from 3.55 to −21.57‰, with dissolved organic carbon (DOC) following the trends of DIC. Gas phase CO2 only occurs within ~20 km of the arc; δ13CVPDB values varied from −0.84 to −5.23‰. Onsite, pH, conductivity, temperature and dissolved oxygen (DO) were measured; pH ranged from 0.9–10.0, conductivity from 200–91,900 μS/cm, temperatures from 23–89 °C and DO from 2–84%. Data were used to develop a model which suggests that ~91 ± 4.0% of carbon released from the slab/mantle beneath the Costa Rican forearc is sequestered within the crust by calcite deposition with an additional 3.3 ± 1.3% incorporated into autotrophic biomass., Measurement(s)temperature of air • pH • Total Organic Carbon • carbon-13 atom • dissolved inorganic carbon content • dissolved organic carbon content • carbon dioxide • helium-3 atom • helium-4 atom • methaneTechnology Type(s)Temperature Probe Device • pH sensor • mass spectrometerFactor Type(s)time • location where data was collectedSample Characteristic - Environmentvolcanic arc • fumarole • hot spring • seepSample Characteristic - LocationCosta Rica Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.10293350

Recently we found that acute treatment with Oxotremorine (Oxo), a non-selective mAChRs agonist, up-regulates heat shock proteins and activates their transcription factor heat shock factor 1 in the rat hippocampus. Here we aimed to investigate: a) if acute treatment with Oxo may regulate pro-inflammatory or anti-inflammatory cytokines and oxidative stress in the rat hippocampus; b) if chronic restraint stress (CRS) induces inflammatory or oxidative alterations in the hippocampus and whether such alterations may be affected by chronic treatment with Oxo. In the acute experiment, rats were injected with single dose of Oxo (0.4 mg/kg) and sacrificed at 24 h, 48 h and 72 h. In the CRS experiment, the rats were exposed for 21 days to the CRS and then were treated with Oxo (0.2 mg/kg) for further 10 days. The acute Oxo treatment showed an ability to significantly reduce reactive oxygen species (ROS), singlet oxygen (1O2), pro-inflammatory cytokines levels (IL-1β and IL-6) and phosphorylated NF-κB-p65. Acute Oxo treatment also increased superoxide dismutase (SOD)-2 protein levels and stimulated SOD activity. No differences were detected in the anti-inflammatory cytokine levels, including IL-10 and TGF-β1. In the group of rats exposed to the CRS were found increased hippocampal IL-1β and IL-6 levels, together with a reduction of SOD activity level. These changes produced by CRS were counteracted by chronic Oxo treatment. In contrast, the upregulation of ROS and 1O2 levels in the CRS group was not counteracted by chronic Oxo treatment. The results revealed a hippocampal anti-inflammatory and antioxidant effect of Oxo treatment in both basal conditions and anti-inflammatory in the CRS rat model.

Background inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), are prevalent and debilitating health problems worldwide. Due to the adverse effects of classical treatment for IBD, therapeutic options and approaches for these diseases continue to evolve. Guanosine, a guanine-based purine, is an extracellular signalling molecule that seems to exert anti-inflammatory and antioxidative effects in several in vivo and in vitro injury models. The aim of the present study was to investigate whether exogenous guanosine may have protective effects on 2,4-dinitrobenzene sulfonic acid (DNBS)-induced Colitis in rat. Methods Experimental Colitis was induced by intrarectal administration of 0.25 ml of DNBS in 50% EtOH solution. After the induction of colitis animal received daily for 6 consecutive days i.p injection of guanosine (8 mg/kg). The effects of guanosine on DNBS-induced colitis were assessed by determination of body weight loss, stool consistency, colon weight/length, histological analysis, Furthermore the myeloperoxidase activity was biochemically evaluated and the mRNA expression of pro-inflammatory cytokines was detected by real-time quantitative reverse transcription PCR (qRT-PCR). In addition, nuclear factor-κB (NF-κB) p65 protein expression levels in colon tissues was investigated using Western blotting and markers of oxidative and nitrosative stress were detected. Results Inflammation in DNBS-rat is characterised by symptoms of losing body weight, loose feces/watery diarrhoea, leukocyte infiltration upregulation of proinflammatory cytokines, oxidative and nitrosative stress. Treatment with guanosine (8 mg/kg) significantly ameliorated the severity of DNBS-induced colitis as evidenced by the reduction in body weight loss and in diarrhoea. Guanosine also prevented the macroscopic and microscopic damage to the colonic mucosa, and the increase in myeloperoxidase activity induced by DNBS. Furthermore, the guanosine treated colitis rats also exhibited a lower mRNA level of pro-inflammatory cytokines, namely interleukin-1β , interleukin-6 and tumour necrosis factor-α. Importantly, the ameliorative effect of guanosine was related to an inhibition of the NF-κB signalling pathway by downregulating the expression levels of NF-κB p-65, and to a reduction of DNBS increased levels of reactive oxygen species and nitrite. Conclusion Overall these results indicate that guanosine is able to alleviate colonic inflammation in DNBS- rats mainly by down-regulation of the NF-κB signalling pathway and of the production of anti-inflammatory cytokines, reactive oxygen species and nitrite. Further studies are encouraging for disclosure guanosine as a novel drug candidate for the treatment of colonic inflammation.

Recent evidences suggest thet insulin delivery to the brain can be an important pharmacological therapy for some neurodegenerative pathologies, including Alzheimer disease (AD)

Crosslinked xyloglucan-poly(vinyl alcohol) based hydrogel films have been synthetized and characterized for wound healing applications. Polyvinyl alcohol (PVA) and glycerol (Gro) were added to have an optimal combination of softness, conformability and resilience. Physical hydrogel have been transformed into permanent covalent hydrogels by reaction with glutaraldehyde (GA). Chemical and physical properties of the films have been analyzed by different technique. Moreover, biocompatibility of a selected formulation was assessed in vitro by investigating different aspects, such as cell viability, oxidative stress, mitochondrial dysfunction and specific stress biomarkers. Partial adhesiveness was demonstrated by performing different attaching assays and phalloidin staining. After interaction with blood the hemocompatibility of the XG-PVA film was evaluated by using a multiparametric approach. Antimicrobial activity of the film against Escherichia coli (E.coli) was tested, and we found that XG-PVA film promotes bacterial retentivity and provides mechanical protection against bacterial infiltration. After loading the film with ampicillin, an inhibitory E. coli growth zone was observed. All together these results indicate that the manufactured film is a promising material to be tested in vivo for wound healing applications

In questo lavoro sono stati preparati film sottili di idrogelo (reticolati fisicamente o chimicamente) a base di xyloglucano (XG) e XG/polivinilalcol (PVA), a cui si è aggiunto glicerolo come plasticizzante. Lo xyloglucano è un polisaccaride di origine vegetale, caratterizzato da una catena principale di (1,4)--Dglucosio con ramificazioni laterali di (1-6)-α-xilosio, parzialmente sostituite con (1-2)–β galattosio. E’ stata indagata la possibilità di modulare la densità di reticolazione dell’idrogelo per ottenere il miglior compromesso tra resistenza meccanica e flessibilità, l’integrità strutturale nel tempo e la capacità di assorbire fluidi biologici o trattenere l’umidità. Inoltre, ne è stata verificata la biocompatibilità ed emocompatibilità, la permeabilità ai batteri e le proprietà bioadesive.

Background:Since antidopaminergic drugs are pharmacological agents employed in the management of gastrointestinal motor disorders at all ages, we investigated whether the enteric dopaminergic system may undergo developmental changes after birth.Methods:Intestinal mechanical activity was examined in vitro as changes in isometric tension.Results:In 2-d-old (P2) mice, dopamine induced a contractile effect, decreasing in intensity with age, replaced, at the weaning (day 20), by a relaxant response. Both responses were tetrodotoxin (TTX)-insensitive. In P2, dopaminergic contraction was inhibited by D1-like receptor antagonist and mimicked by D1-like receptor agonist. In 90-d-old (P90) mice, the relaxation was reduced by both D1- and D2-like receptor antagonists, and mimicked by D1- and D2-like receptor agonists. In P2, contraction was antagonized by phospholipase C inhibitor, while in P90 relaxation was antagonized by adenylyl cyclase inhibitor and potentiated by phospholipase C inhibitor. The presence of dopamine receptors was assessed by immunofluorescence. Quantitative real-time polymerase chain reaction (qRT-PCR) revealed a significant increase in D1, D2, and D3 receptor expression in proximal intestine with the age.Conclusion:In mouse small intestine, the response to dopamine undergoes developmental changes shifting from contraction to relaxation at weaning, as the consequence of D2-like receptor recruitment and increased expression of D1 receptors.

Angiotensin II, the main effector of renin angiotensin system, plays an important role in the inflammatory process and most of its effects are mediated through the AT1 receptor activation. However, the knowledge about the AT2 receptor involvement in this process is still evolving. We previously found that in an experimental model of colitis, AT2 receptor activation can contribute to the impairment of the muscle contractility in vitro in the course of inflammation. Here, we investigated the potential alleviating effects of the in vivo treatment of PD123319 (1-[[4-(Dimethylamino)-3-methylphenyl]methyl]-5-(diphenylacetyl)-4,5,6,7- tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid ditrifluoroacetate), AT2 receptor antagonist, in 2,4-dinitrobenzene sulfonic acid (DNBS)-induced rat model of colitis. The effects of i.p PD123319 (0.3, 3 and 10 mg/kg) administration to rats subjected to intra-rectal DNBS instillation were investigated. The study revealed that the colon injury and the inflammatory signs were ameliorated by PD123319 when visualized by the histopathological examination. The colon shortening, myeloperoxidase activity, and colonic expression of IL-1β, IL-6 and iNOS were downregulated in a dose-dependent manner in DNBS-induced colitis rats treated with PD123319 and the anti-oxidant defense machinery was also improved. The mechanism of these beneficial effects was found in the ability of PD123319 to inhibit NF-κB activation induced by DNBS. The colonic contractility in inflamed tissues was also improved by PD123319 treatment. In conclusion, our data have demonstrated previously that undescribed proinflammatory effects for the AT2 receptors in DNBS-induced colitis in rats in which they are mediated likely by NF-κB activation and reactive oxygen species generation. Moreover, when the inflammatory process is mitigated by the AT2 receptor antagonist treatment, the smooth muscle is able to recover its functionality.

Polyvinylpyrrolidone (PVP) has probably been one of the most utilized pharmaceutical polymers with applications ranging from a blood plasma substitute to nanoparticle drug delivery, since its synthesis in 1939. It is a highly biocompatible, non-toxic and transparent film forming polymer. Although high solubility of PVP in aqueous environment is advantageous, it still poses several problems for some applications in which sustained targeting and release are needed or hydrophobic drug inclusion and delivery systems are to be designed. In this study, we demonstrate that a common dietary phenolic antioxidant, p-coumaric acid (PCA), can be combined with PVP covering a wide range of molar ratios by solution blending in ethanol, forming new transparent biomaterial films with antiseptic and antioxidant properties. PCA not only acts as an effective natural plasticizer but also establishes H-bonds with PVP increasing its resistance to water dissolution. PCA could be released in a sustained manner up to a period of 3 days depending on the PVP/PCA molar ratio. Sustained drug delivery potential of the films was studied using methylene blue and carminic acid as model drugs, indicating that the release can be controlled. Antioxidant and remodeling properties of the films were evaluated in vitro by free radical cation scavenging assay and in vivo on a murine model, respectively. Furthermore, the material resorption of films was slower as PCA concentration increased, as observed from the in vivo full-thickness excision model. Finally, the antibacterial activity of the films against common pathogens such as Escherichia coli and Staphylococcus aureus and the effective reduction of inflammatory agents such as matrix metallopeptidases were demonstrated. All these properties suggest that these new transparent PVP/PCA films can find a plethora of applications in pharmaceutical sciences including skin and wound care.