Glycyrrhizin for topical use and prophylaxis of COVID-19: an interesting pharmacological perspective.

COVID-19, the disease caused by the SARS - CoV - 2 pathogen, is currently a pandemic. At the moment there is not an available vaccine, so, scientific community is looking for strategies and drugs to implement prevention and prophylaxis. Several compounds are examined for this purpose. Glycyrrhizin, an alkaloid extracted from licorice plant (glycyrriza glabra), is one of the most studied molecules, both for its peculiar biological functions and for its pharmacological effects. This brief review aims to highlight the characteristics of glycyrrhizin for topical use on the nasal and ocular surfaces. The anti-inflammatory activity, the ability to inhibit the accumulation of ROS, the antiviral property, but, above all, the ability to bind the ACE receptor and the SARS - CoV-2 protein S in the extracellular environment make Glycyrrhizzin for topical use a compound with a high prophylactic potential for SARS - CoV - 2 infection, also due to its low cost and the absence of significant side effects.

Non-human primates use combined rules when deciding under ambiguity.

Decision outcomes in unpredictable environments may not have exact known probabilities. Yet the predictability level of outcomes matters in decisions, and animals, including humans, generally avoid ambiguous options. Managing ambiguity may be more challenging and requires stronger cognitive skills than decision-making under risk, where decisions involve known probabilities. Here we compare decision-making in capuchins, macaques, orangutans, gorillas, chimpanzees and bonobos in risky and ambiguous contexts. Subjects were shown lotteries (a tray of potential rewards, some large, some small) and could gamble a medium-sized food item to obtain one of the displayed rewards. The odds of winning and losing varied and were accessible in the risky context (all rewards were visible) or partially available in the ambiguous context (some rewards were covered). In the latter case, the level of information varied from fully ambiguous (individuals could not guess what was under the covers) to predictable (individuals could guess). None of the species avoided gambling in ambiguous lotteries and gambling rates were high if at least two large rewards were visible. Capuchins and bonobos ignored the covered items and gorillas and macaques took the presence of potential rewards into account, but only chimpanzees and orangutans could consistently build correct expectations about the size of the covered rewards. Chimpanzees and orangutans combined decision rules according to the number of large visible rewards and the level of predictability, a process resembling conditional probabilities assessment in humans. Despite a low sample size, this is the first evidence in non-human primates that a combination of several rules can underlie choices made in an unpredictable environment. Our finding that non-human primates can deal with the uncertainty of an outcome when exchanging one food item for another is a key element to the understanding of the evolutionary origins of economic behaviour. This article is part of the theme issue 'Existence and prevalence of economic behaviours among non-human primates'.

Toward stomatal-flux based forest protection against ozone: The MOTTLES approach.

European standards for the protection of forests from ozone (O3) are based on atmospheric exposure (AOT40) that is not always representative of O3 effects since it is not a proxy of gas uptake through stomata (stomatal flux). MOTTLES "MOnitoring ozone injury for seTTing new critical LEvelS" is a LIFE project aimed at establishing a permanent network of forest sites based on active O3 monitoring at remote areas at high and medium risk of O3 injury, in order to define new standards based on stomatal flux, i.e. PODY (Phytotoxic Ozone Dose above a threshold Y of uptake). Based on the first year of data collected at MOTTLES sites, we describe the MOTTLES monitoring station, together with protocols and metric calculation methods. AOT40 and PODY, computed with different methods, are then compared and correlated with forest-health indicators (radial growth, crown defoliation, visible foliar O3 injury). For the year 2017, the average AOT40 calculated according to the European Directive was even 5 times (on average 1.7 times) the European legislative standard for the protection of forests. When the metrics were calculated according to the European protocols (EU Directive 2008/50/EC or Modelling and Mapping Manual LTRAP Convention), the values were well correlated to those obtained on the basis of the real duration of the growing season (i.e. MOTTLES method) and were thus representative of the actual exposure/flux. AOT40 showed opposite direction relative to PODY. Visible foliar O3 injury appeared as the best forest-health indicator for O3 under field conditions and was more frequently detected at forest edge than inside the forest. The present work may help the set-up of further long-term forest monitoring sites dedicated to O3 assessment in forests, especially because flux-based assessments are recommended as part of monitoring air pollution impacts on ecosystems in the revised EU National Emissions Ceilings Directive.

Engineered cross-reacting nanobodies simplify comparative oncology between humans and dogs.

Antibodies cross-reacting with homologue antigens in different species would be essential reagents for the development of comparative oncology studies. In comparison with conventional immunoglobulin Gs, recombinant nanobodies (single-domain variable regions of heavy-chain only antibodies of Camelidae origin) can be easily isolated in vitro and engineered into a variety of reagents with optimized characteristics for different research and clinical applications. We recovered an anti-human epidermal growth factor receptor 2 (anti-HER2) nanobody from a naïve llama library by direct panning on whole cells and expressed it fused to Fc and green fluorescent protein. These immunoreagents were assessed by flow cytometry and immunofluorescence with both human and canine cells overexpressing HER2 and its canine homologue dog epidermal growth factor receptor 2. The reported data illustrate the potential of using this class of antibodies in comparative oncology and suggest some development perspectives enabled by in vitro panning of pre-immune nanobody libraries.

Health risk assessment of exposure to the Middle-Eastern Dust storms in the Iranian megacity of Kermanshah.

OBJECTIVE: This study assessed the effects of particulate matter (PM), equal or less than 10 µm in aerodynamic diameter (PM10), from the Middle-Eastern Dust events on public health in the megacity of Kermanshah (Iran). STUDY DESIGN: This study used epidemiological modeling and monitored ambient air quality data to estimate the potential PM10 impacts on public health. METHODS: The AirQ2.2.3 model was used to calculate mortality and morbidity attributed to PM10 as representative of dust events. Using Visual Basic for Applications, the programming language of Excel software, hourly PM10 concentrations obtained from the local agency were processed to prepare input files for the AirQ2.2.3 model. RESULTS: Using baseline incidence, defined by the World Health Organization, the number of estimated excess cases for respiratory mortality, hospital admissions for chronic obstructive pulmonary disease, for respiratory diseases, and for cardiovascular diseases were 37, 39, 476, and 184 persons, respectively, from 21st March, 2014 to 20th March, 2015. Furthermore, 92% of mortality and morbidity cases occurred in days with PM10 concentrations lower than 150 µg/m3. The highest percentage of person-days occurred for daily concentrations range of 100-109 µg/m3, causing the maximum health end-points among the citizens of Kermanshah. CONCLUSIONS: Calculating the number of cumulative excess cases for mortality or morbidity attributed to PM10 provides a good tool for decision and policy-makers in the field of health care to compensate their shortcomings particularly at hospital and healthcare centers for combating dust storms. To diminish these effects, several immediate actions should be managed in the governmental scale to control dust such as spreading mulch and planting new species that are compatible to arid area.

A multi-sites analysis on the ozone effects on Gross Primary Production of European forests.

Ozone (O3) is both a greenhouse gas and a secondary air pollutant causing adverse impacts on forests ecosystems at different scales, from cellular to ecosystem level. Specifically, the phytotoxic nature of O3 can impair CO2 assimilation that, in turn affects forest productivity. This study aims to evaluate the effects of tropospheric O3 on Gross Primary Production (GPP) at 37 European forest sites during the time period 2000-2010. Due to the lack of carbon assimilation data at O3 monitoring stations (and vice-versa) this study makes a first attempt to combine high resolution MODIS Gross Primary Production (GPP) estimates and O3 measurement data. Partial Correlations, Anomalies Analysis and the Random Forests Analysis (RFA) were used to quantify the effects of tropospheric O3 concentration and its uptake on GPP and to evaluate the most important factors affecting inter-annual GPP changes. Our results showed, along a North-West/South-East European transect, a negative impact of O3 on GPP ranging from 0.4% to 30%, although a key role of meteorological parameters respect to pollutant variables in affecting GPP was found. In particular, meteorological parameters, namely air temperature (T), soil water content (SWC) and relative humidity (RH) are the most important predictors at 81% of test sites. Moreover, it is interesting to highlight a key role of SWC in the Mediterranean areas (Spanish, Italian and French test sites) confirming that, soil moisture and soil water availability affect vegetation growth and photosynthesis especially in arid or semi-arid ecosystems such as the Mediterranean climate regions. Considering the pivotal role of GPP in the global carbon balance and the O3 ability to reduce primary productivity of the forests, this study can help in assessing the O3 impacts on ecosystem services, including wood production and carbon sequestration.

Features of endothelial dysfunction in umbilical cord vessels of women with gestational diabetes.

BACKGROUND AND AIMS: Gestational diabetes (GDM) is associated with increased oxidative stress and overexpression of inflammatory cytokines, both of which might lead to endothelial dysfunction and vascular disease. As such, GDM could be viewed as a sort of 'short lived' metabolic syndrome. As umbilical cord vessels represent a suitable model for the study of vascular alterations brought about by GDM, the aim of the present work was to characterize the phenotype of human umbilical vein endothelial cells (HUVECs) chronically exposed to hyperglycaemia and to a pro-inflammatory environment during pregnancy so as to identify molecular modifications of cellular homoeostasis eventually impacting on endothelial dysfunction. METHODS AND RESULT: Tissue specimens and HUVECs were obtained from umbilical cords of GDMand control women. As compared to controls, GD-HUVEC exhibited enhanced monocyte adhesion and vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1(ICAM-1) expression and exposure on plasma membrane after tumour necrosis factor-alpha(TNF-α) stimulation (Western blot, flow cytometer). As compared to control cells, GD-HUVEC in basal conditions exhibited enhanced monocyte adhesion, nitric oxide synthase (NOS) expression and activity (eNOS Real-Time polymerase chain reaction, Western Blot for eNOS total protein and monomers/dimers ratio, conversion of [3H]-L-arginine in [3H]-L-citrulline), increased O(-)(2)egeneration together with increased NT levels (immunofluorescence) and reduced NO bioavailability(guanosine 3',5'-monophosphate (cGMP) production, EIA). Furthermore, immunohistochemistry revealed increased eNOS and NT immunoreactivity in GD umbilical cords. CONCLUSION: Endothelial cells exposed in vivo even transiently to hyperglycaemia, oxidative stress and inflammation exhibit durable pro-atherogenic modifications.

Transcriptome analysis of human primary endothelial cells (HUVEC) from umbilical cords of gestational diabetic mothers reveals candidate sites for an epigenetic modulation of specific gene expression.

Within the complex pathological picture associated to diabetes, high glucose (HG) has "per se" effects on cells and tissues that involve epigenetic reprogramming of gene expression. In fetal tissues, epigenetic changes occur genome-wide and are believed to induce specific long term effects. Human umbilical vein endothelial cells (HUVEC) obtained at delivery from gestational diabetic women were used to study the transcriptomic effects of chronic hyperglycemia in fetal vascular cells using Affymetrix microarrays. In spite of the small number of samples analyzed (n=6), genes related to insulin sensing and extracellular matrix reorganization were found significantly affected by HG. Quantitative PCR analysis of gene promoters identified a significant differential DNA methylation in TGFB2. Use of Ea.hy926 endothelial cells confirms data on HUVEC. Our study corroborates recent evidences suggesting that epigenetic reprogramming of gene expression occurs with persistent HG and provides a background for future investigations addressing genomic consequences of chronic HG.

Consistency of dominance rank order: a comparison of David's Scores with I&SI and Bayesian methods in macaques.

In nonhuman primate social groups, dominance ranks are usually assigned to individuals based on outcomes of dyadic agonistic encounters. Multiple approaches have been used, but currently there is no consensus. One approach, David's Scores (DS), offers dual advantages of yielding cardinal scores that may in turn be used to compute hierarchical steepness. Here we correlate rank orders yielded by DS with those yielded by both the traditionally used I&SI approach and the recently proposed parametric Bayesian approach. We use six datasets for female macaques (three despotic and three tolerant groups), and 90 artificially generated datasets modeling macaque groups. We also use the artificial datasets to determine the impact of three characteristics (group size, interaction frequency, and directional asymmetry of aggression) on the magnitude of correlation coefficients, and assess the relative utility of two indices used to compute DS: Dij versus Pij. DS-based rank orders were strongly positively correlated with those yielded by the other two approaches for five out of the six macaque datasets, and for the majority of artificial datasets. Magnitudes of correlation coefficients were unrelated to group size or interaction frequency, but increased with directional asymmetry, suggesting methodological inconsistencies were more likely when dyads had more frequent reversals in directions of aggression. Finally, rank orders calculated using the Dij and Pij indices were similarly consistent with orders from other methods. We conclude that DS offers consistent estimates of rank orders, except perhaps in groups with very low levels of aggression asymmetry. In such "tolerant" groups, we suggest that the relatively greater methodological variability in rank orders may reflect behavioral characteristics of tolerant groups rather than computational inconsistencies between methods. We hypothesize that this quality may be quantified using posterior probability scores of Bayesian rank orders and may also index macaque social styles.

Perspectives offered by single-domain antibodies in clinical diagnostic of pediatric tumors.

The results accrued in the last few years have clearly showed that recombinant antibodies, and specifically single- domain antibodies, represent valid alternatives to conventional IgGs for in vivo imaging. It does not simply mean that antibody fragments can substitute full-length antibodies, but that they are substantially more suitable for some applications and can perform other functions for which no real alternative is available. Brain imaging with multi-functional probes is an evident example, but the promising results obtained with micro-PET and -SPECT in murine models could lead in short time to a revolutionary change in clinical diagnostics. Brilliant applications of single-domain antibody-dependent imaging have enabled us to understand how the tracer mass and avidity can be engineered to modulate pharmacokinetic features such as clearance, tumor penetration, and binding affinity with the aim of optimizing specific responses. The potential of these reagents and the increasing interest for them is evidenced by the exponential growth of publications and the multiplication of the proposed applications in which they are used. This review wishes to provide an update of this fast moving subject and to indicate what may be the next foreseeable technical progress.

Suitability of two types of organic wastes for the growth of sclerophyllous shrubs on limestone debris: a mesocosm trial.

This study investigated whether overlaying organic wastes directly on limestone debris allowed the growth of sclerophyllous shrubs; the aim was to explore the feasibility of rehabilitation of sites destroyed by quarrying activity. In an open air mesocosm experiment two types of organic material were compared: compost from municipal wastes (C) and a mixture of compost and poultry manure added with wheat husk (C-PW). Mesocosms were pots (1m diameter, 60cm height) containing limestone debris covered by the organic material. Seven mesocosms with C and seven mesocosms with C-PW were planted with sclerophyllous shrubs (Laurus nobilis L., Phillyrea angustifolia L. and Quercus ilex L.). The substrates were characterised in terms of chemical and physical parameters, microbial activity and biomass, and total and active fungal biomass. Shrub photosynthetic performance and growth were evaluated. Over the whole experimental period, organic matter mineralization was higher in C-PW. Microbial biomass and respiration were higher in C-PW than in C but after one year no statistically significant difference between the two substrates occurred. Fungal mycelium was a minor fraction of the microbial community in both types of substrates and decreased dramatically after setting up the mesocosms. The metabolic quotient was higher in C suggesting more stressful conditions as compared to C-PW. Both substrates allowed shrub growth; however photosynthetic rates and the increase of plant size were higher on C-PW than on C. The results demonstrated that, as compared to only compost, the mixture of compost and poultry manure added with wheat husk is a substrate more suitable to both microbial processes and plant growth. Therefore a plan to revegetate quarries based on the use of organic wastes as a substrate for sclerophyllous shrubs could be feasible and, what is more, helpful to mitigate the environmental impact of organic wastes disposal.

Multiple cerebral aneurysms associated with atrial myxoma. A case report.

Cardiac myxoma is a tumor of mesenchymal origin accounting for half of all primary cardiac neoplasms. Intracranial involvement by atrial myxoma is a rare cause of neurologic deficit. When the myxoma arises in the left atrium, systemic emboli from a cardiac myxoma can lead to infarction, cerebral hemorrhage and aneurysm formation. In the light of the potentially preventable nature of these lesions, the diagnosis of myxomatous aneurysms should be considered in any patient with neurologic symptoms and a history of cardiac myxoma. Because aneurysms are often stable over several years, conservative management with careful clinical and radiological follow-up with MRI and angiography seems sensible. We describe a case in which MR imaging and angiography were used to diagnose multiple cerebral aneurysms caused by left atrial myxoma.

Effects of recombinant protein misfolding and aggregation on bacterial membranes.

The expression of recombinant proteins is known to induce a metabolic rearrangement in the host cell. We used aggregation-sensitive model systems to study the effects elicited in Escherichia coli cells by the aggregation of recombinant glutathione-S-transferase and its fusion with the green fluorescent protein that, according to the expression conditions, accumulate intracellularly as soluble protein, or soluble and insoluble aggregates. We show that the folding state of the recombinant protein and the complexity of the intracellular aggregates critically affect the cell response. Specifically, protein misfolding and aggregation induce changes in specific host proteins involved in lipid metabolism and oxidative stress, a reduction in the membrane permeability, as well as a rearrangement of its lipid composition. The temporal evolution of the host cell response and that of the aggregation process pointed out that the misfolded protein and soluble aggregates are responsible for the membrane modifications and the changes in the host protein levels. Interestingly, native recombinant protein and large insoluble aggregates do not seem to activate stress markers and membrane rearrangements.

Recurrent Intraventricular Hemorrhages Caused by an AVM Detected by Angiography with Initially Normal Angiogram.

Primary intraventricular haemorrhage (PIVH) is an uncommon type of non-traumatic cerebral haemorrhage limited to the ventricular system arising in adults and children, with diverse aetiology and variable course. Vascular malformations account for 34% of PIVH, whereas no cause is found in 21-47%. When a primary intraventricular haemorrhage is detected in a young patient an underlying lesion such as an arteriovenous malformation (AVM) must be ruled out. The diagnosis may be suspected when there is sudden onset of headache, nausea and vomiting with or without a reduced level of consciousness. Nevertheless, even if clinical features suggest the diagnosis of PIVH, cerebral computed tomography (CT) scan is required for confirmation, and magnetic resonance imaging (MRI) and catheter angiography are necessary to establish the aetiology. We describe a case of isolated recurrent intraventricular haemorrhages caused by AVM detected by diagnostic intracranial angiography with no abnormality demonstrated on angiography four years earlier.

Measuring, modelling and testing ozone exposure, flux and effects on vegetation in southern European conditions--what does not work? A review from Italy.

Ozone (O3) exposure at Italian background sites exceeds UN/ECE concentration-based critical levels (CLe(c)), if expressed in terms of AOT40. Yet the occurrence of adverse effects of O3 on forests and crops is controversial. Possible reasons include (i) ability of response indicators to provide an unbiased estimate of O3 effects, (ii) setting of current CLe(c) in terms of cut-off value and accumulation level, (iii) response functions adopted to infer a critical level, (iv) environmental limitation to O3 uptake and (v) inherent characteristics of Mediterranean vegetation. In particular, the two latter points suggest that critical levels based on accumulated stomatal flux (CLe(f)) can be a better predictor of O3 risk than CLe(c). While this concept is largely acknowledged, a number of factors may limit its applicability for routine monitoring. This paper reviews levels, uptake and vegetation response to O3 in Italy over recent years to discuss value, uncertainty and feasibility of different approaches to risk assessment.

A multi-biomarker analysis of DNA damage in automobile painters.

The genotoxic effects associated with automobile painting were analyzed using a panel of biomarkers. Chromosomal aberrations (CAs), sister chromatid exchange (SCE), and micronuclei were evaluated in 25 car painters (12 smokers, 13 nonsmokers) working in different automobile paint-shops in Italy and in 37 control subjects. The controls were healthy blood donors (14 smokers, 23 non-smokers) that were matched with the experimental population for gender and age. Air samples were analyzed regularly at the work places, and elevated concentrations of benzene and toluene were detected consistently. The exposed group had higher frequencies of CAs (both chromosome- and chromatid-type), micronuclei, and SCE (P < 0.5 - P < 0.001). Furthermore, exposed and control subjects were also genotyped for GSTM1 and GSTT1 polymorphism. No significant associations were detected between the biomarker responses and either the GSTM1 or GSTT1 genotype of the subjects, but the small sample size does not allow definite conclusions on the relationship between the genetic polymorphism and the biomarkers. The results indicate that automobile painters have increased levels of clastogenic and possible aneugenic damage and that smoking may be a confounding factor for the responses.

Lichens as polycyclic aromatic hydrocarbon bioaccumulators used in atmospheric pollution studies.

The aim of this work has been to determine the possibility of using lichens as polycyclic aromatic hydrocarbon (PAH) bioaccumulators for the evaluation of atmospheric pollution in the city of Rieti. A lichen sample collected in a remote unpolluted area was divided into 18 sub-samples. These were collocated in nine different stations in the city of Rieti and every 5 months the PAH concentrations were determined. Only phenanthrene, anthracene, fluoranthene, pyrene and chrysene were found at concentrations over the limit of quantification. In the meantime a continuous increase of their concentrations was observed.

Influence of a low background radiation environment on biochemical and biological responses in V79 cells.

We present the results of an experiment aimed at comparing the effects of different background radiation environments on metabolism and responses to gamma-rays and cycloheximide of cultured mammalian cells. Chinese hamster V79 cells were maintained in exponential growth in parallel for up to 9 months at the Istituto Superiore di Sanità (ISS) and at the INFN-Gran Sasso underground Laboratory (LNGS) where exposure due to gamma-rays and to radon was reduced by factors of about 70 and 25, respectively. After 9 months the cells grown at the LNGS (cumulative gamma dose about 30 microGy, average radon concentration around 5 Bq/m(3)), compared to the cells grown at the ISS (cumulative gamma-ray dose about 2 mGy, average radon concentration around 120 Bq/m(3)), exhibited i). a significant increase of the cell density at confluence, ii). a significantly higher capacity to scavenge organic and inorganic hydroperoxides but a reduced scavenging capacity towards superoxide anions and iii). an increase in both the basal hprt mutation frequency and sensitivity to the mutagenic effect of gamma-rays. The cells grown at the LNGS also showed a greater apoptotic sensitivity starting at the third month of culture, that was no longer detected after 9 months. Overall, these data suggest a role of background ionizing radiation in determining an adaptive response, although they cannot be considered conclusive.