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Abstract Vitamin B6 is a water-soluble vitamin which possesses antioxidant properties. Its catalytically active form, pyridoxal 5’-phosphate (PLP), is a crucial cofactor for DNA and amino acid metabolism. The inverse correlation between vitamin B6 and cancer risk has been observed in several studies, although dietary vitamin B6 intake sometimes failed to confirm this association. However, the molecular link between vitamin B6 and cancer remains elusive. Previous work has shown that vitamin B6 deficiency causes chromosome aberrations (CABs) in Drosophila and human cells, suggesting that genome instability may correlate the lack of this vitamin to cancer. Here we provide evidence in support of this hypothesis. Firstly, we show that PLP deficiency, induced by the PLP antagonists 4-deoxypyridoxine (4DP) or ginkgotoxin (GT), promoted tumorigenesis in eye larval discs transforming benign Ras V12 tumors into aggressive forms. In contrast, PLP supplementation reduced the development of tumors. We also show that low PLP levels, induced by 4DP or by silencing the sgll PNPO gene involved in PLP biosynthesis, worsened the tumor phenotype in another Drosophila cancer model generated by concomitantly activating RasV12 and downregulating Discs-large (Dlg) gene. Moreover, we found that Ras V12 eye discs from larvae reared on 4DP displayed CABs, reactive oxygen species (ROS) and low catalytic activity of serine hydroxymethyltransferase (SHMT), a PLP-dependent enzyme involved in thymidylate (dTMP) biosynthesis, in turn required for DNA replication and repair. Feeding Ras V12 4DP-fed larvae with PLP or ascorbic acid (AA) plus dTMP, rescued both CABs and tumors. The same effect was produced by overexpressing catalase in Ras V12 Dlg RNAi 4DP-fed larvae, thus allowing to establish a relationship between PLP deficiency, CABs, and cancer. Overall, our data provide the first in vivo demonstration that PLP deficiency can impact on cancer by increasing genome instability, which is in turn mediated by ROS and reduced dTMP levels.

In recent years, the invasive Atlantic blue crab (Callinectes sapidus) has increased its spread throughout the Mediterranean Sea, threatening native biodiversity and local economies. This study aimed to valorize C. sapidus sampled in Sicily by utilizing its exoskeleton as a source of chitosan, astaxanthin, and bio-phenolic compounds. These biomolecules were evaluated for their reducing, radical scavenging, and antitumor activity. The ferric ion reducing antioxidant power (FRAP) and the free radical scavenging activity against radical 2,2-Diphenyl-1-picrylhydrazyl (DPPH) were significantly higher for chitosan (3.16 ± 0.10 mg AAE/g and 8.1 ± 0.10 µmol TE/g). No significant differences were observed among the tested biomolecules in their activity in scavenging the radical 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). Both bio-phenolic compounds and astaxanthin exhibited dose-dependent cytotoxicity on CaCo-2 (IC50 = 12.47 and 18 µg/mL) and HepG2 (IC50 = 10.25 and 1.26 µg/mL) cell lines, while only bio-phenols showed no cytotoxic effect on differentiated CaCo-2 cells up to 20 µg/mL. These findings highlight the value of blue crab by-products in supporting a circular economy, offering a sustainable approach to managing this invasive species while providing bioactive compounds with promising medical and nutraceutical applications.

This study evaluates, for the first time, the reducing capacity, radical scavenger activity, and in vitro antitumor and anti-inflammatory effects of chitosan, astaxanthin, and bio-phenols extracted from the exoskeleton of Sicilian Procambarus clarkii, the most widespread species of invasive crayfish in the Mediterranean region. Among the extracted compounds, astaxanthin exhibited the highest antioxidant activity in all assays. Chitosan and polyphenols demonstrated reducing and radical scavenging activity; chitosan showed significant ferric ion reducing capacity in the FRAP test, while bio-phenolic compounds displayed notable radical scavenging activity in the DPPH and ABTS assays. Both astaxanthin and polyphenols showed dose-dependent cytotoxicity on two different cancer cell lines, with IC50 values of 1.45 µg/mL (phenolic extract) and 4.28 µg/mL (astaxanthin extract) for HepG2 cells and 2.45 µg/mL (phenolic extract) and 4.57 µg/mL (astaxanthin extract) for CaCo-2 cells. The bio-phenolic extract also showed potential anti-inflammatory effects in vitro by inhibiting nitric oxide production in inflamed RAW 264.7 macrophages, reducing the treated/control NO ratio to 77% and 74% at concentrations of 1.25 and 1.5 μg/mL, respectively. These results suggest that P. clarkii exoskeletons could be a valuable source of bioactive molecules for biomedical, pharmaceutical, and nutraceutical application while contributing to the sustainable management of this invasive species.

From the perspective of circular economy, it is extremely useful to recycle waste products for human health applications. Among the health-beneficial properties of bioactive phyto-compounds, grape pomace represents a precious source of bioactive molecules with potential antitumor properties. Here, we describe the effects of a Sicilian grape pomace hydroalcoholic extract (HE) in colon and breast cancer cells. The characterization of HE composition revealed the predominance of anthoxanthins and phenolic acids. HE treatment was more effective in reducing the viability of colon cancer cells, while breast cancer cells appeared more resistant. Indeed, while colon cancer cells underwent apoptosis, as shown by DNA fragmentation, caspase-3 activation, and PARP1 degradation, breast cancer cells seemed to not undergo apoptosis. To elucidate the underlying mechanisms, reactive oxygen species (ROS) were evaluated. Interestingly, ROS increased in both cell lines but, while in colon cancer, cells’ ROS rapidly increased and progressively diminished over time, in breast cancer, cells’ ROS increase was persistent up to 24 h. This effect was correlated with the induction of pro-survival autophagy, demonstrated by autophagosomes formation, autophagic markers increase, and protection by the antioxidant NAC. The autophagy inhibitor bafilomycin A1 significantly increased the HE effects in breast cancer cells but not in colon cancer cells. Overall, our data provide evidence that HE efficacy in tumor cells depends on a balance between ROS-mediated autophagy and apoptosis. Therefore, inhibiting pro-survival autophagy may be a tool to target those cells that appear more resistant to the effect of HE.

The article deals with the relationship between city, territory, and democracy, starting from the results of an international research, which investigated the peculiar forms of the crisis of the notion of Public in those territories that are marked by a long-date conflict between the state and mafia crime. The research questions areframed onto a perspective arguing that the territory is an elective place to read the traces built throughout the relationship between communities and illegal powers. Those questions have posed the need to investigate the set of confiscated assets by claiming the need for architectural design intervention, aiming at the spatial, linguistic, and symbolic transformations without which their transition to commons cannot be said to be fully accomplished. Referring to the municipal area of Palermo, the architectural design studios faced the background scenario constituted by the almost two thousand cases (a very underestimated number) registered by the National Agency for Seized and Confiscated Assets, and relating to the forms of the Public in a context in which democracy is en panne, where the presence of anti-democratic forces that are not only antagonistic to the state but aim to replace it, is not the exception but the rule. Until its conclusions, the paper deals with the reciprocal feeding relationship between research and design studios and concludes by opening new paths, at the crossroads between the updating of the themes of the droit à la ville and spatial justice, which look at the project as a device for emancipation.

COVID-19 pandemic has caused changes in logistics and mobility. Concerning Italian road mobility, between March and April 2020, there has been a reduction in traffic for both light vehicles and heavy goods vehicles. Italy was the first European country to implement a total lockdown, starting on March 9th, causing a deep contraction in road traffic. This paper explores the main differences in mobility choices before and after the COVID-19 pandemic in 2020. A multi-criteria decision-making method was selected for the analysis of questionnaire survey data. The fuzzy Analytic Hierarchy Process was applied, considering eight mobility types: bus, tram, taxi, train, shared vehicles, multiple modes, walking and car. An evaluation process was adopted for the modal mobility choices of the residents of Sicily, Italy. The results show a significant decline in mobility demand during the first phase of the pandemic, especially in public transport mode. The findings provide a deeper understanding of the need to implement strategies to respect the constraints generated by the pandemic and revive the penalised transport and mobility-related sectors. Furthermore, the study's findings provide valuable insights for the policymakers, both national and local, about the mobility results of the lockdown and can be used as a forecast benchmark for planning the restrictions in the future, in case of another unexpected phenomenon, e.g., pandemic.

An unstoppable shift in the paradigm underlying mankind’s conception of its species’ building modalities is at the root of the interest in embedding greenery in Architecture. The most capable heuristic statute of such a new course is the progressive substitution of Environment for Nature among Design drivers. Within this frame, this paper investigates the hybridisation of greenery and the built environment in the contemporary transformation of large urban highways through a diachronic and comparative approach, referencing international research and expanding its main hypothesis. With this purpose, it reconstructs the hermeneutic reference frame by progressively discussing the theoretical arguments, deepening approaches, and design cases, among which the applicative one elaborated for the transformation of Palermo’s ring road. Article info Received: 25/03/2023; Revised: 30/04/2023; Accepted: 14/05/2023

In recent years, the invasive Atlantic blue crab (Callinectes sapidus) has increased its spread throughout the Mediterranean Sea, threatening native biodiversity and local economies. This study aimed to valorize C. sapidus sampled in Sicily by utilizing its exoskeleton as a source of chitosan, astaxanthin, and bio-phenolic compounds. These biomolecules were evaluated for their reducing, radical scavenging, and antitumor activity. The ferric ion reducing antioxidant power (FRAP) and the free radical scavenging activity against radical 2,2-Diphenyl-1-picrylhydrazyl (DPPH) were significantly higher for chitosan (3.16 ± 0.10 mg AAE/g and 8.1 ± 0.10 µmol TE/g). No significant differences were observed among the tested biomolecules in their activity in scavenging the radical 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). Both bio-phenolic compounds and astaxanthin exhibited dose-dependent cytotoxicity on CaCo-2 (IC50 = 12.47 and 18 µg/mL) and HepG2 (IC50 = 10.25 and 1.26 µg/mL) cell lines, while only bio-phenols showed no cytotoxic effect on differentiated CaCo-2 cells up to 20 µg/mL. These findings highlight the value of blue crab by-products in supporting a circular economy, offering a sustainable approach to managing this invasive species while providing bioactive compounds with promising medical and nutraceutical applications. [ABSTRACT FROM AUTHOR]

This study evaluates, for the first time, the reducing capacity, radical scavenger activity, and in vitro antitumor and anti-inflammatory effects of chitosan, astaxanthin, and bio-phenols extracted from the exoskeleton of Sicilian Procambarus clarkii, the most widespread species of invasive crayfish in the Mediterranean region. Among the extracted compounds, astaxanthin exhibited the highest antioxidant activity in all assays. Chitosan and polyphenols demonstrated reducing and radical scavenging activity; chitosan showed significant ferric ion reducing capacity in the FRAP test, while bio-phenolic compounds displayed notable radical scavenging activity in the DPPH and ABTS assays. Both astaxanthin and polyphenols showed dose-dependent cytotoxicity on two different cancer cell lines, with IC50 values of 1.45 µg/mL (phenolic extract) and 4.28 µg/mL (astaxanthin extract) for HepG2 cells and 2.45 µg/mL (phenolic extract) and 4.57 µg/mL (astaxanthin extract) for CaCo-2 cells. The bio-phenolic extract also showed potential anti-inflammatory effects in vitro by inhibiting nitric oxide production in inflamed RAW 264.7 macrophages, reducing the treated/control NO ratio to 77% and 74% at concentrations of 1.25 and 1.5 μg/mL, respectively. These results suggest that P. clarkii exoskeletons could be a valuable source of bioactive molecules for biomedical, pharmaceutical, and nutraceutical application while contributing to the sustainable management of this invasive species. [ABSTRACT FROM AUTHOR]

This research focuses on how population density may influence the municipal expenditure using a global dataset from UN-Habitat. Specifically, we test its role on different budget categories, including sanitation, waste, water, affordable housing, and security. We find that in general density is likely to be correlated with expenditure. This evidence is not robust across the considered expenditure categories. Rather, population density is likely to influence specific budget items and its explanatory power varies as we consider different measures of it. Among control variables, we point out the significance and magnitude of the regressors related to economic development, which in some cases matters more than density in explaining some expenditure categories. Findings suggest that making cities denser can be a valuable option of urban policy, if the target is expenditure optimization. Nonetheless, this works only when it is combined with a mix of other factors, and location is also considered.

Public transport generally addresses the evident mobility needs and offers an often-irreplaceable service, especially for captive users and other disadvantaged population groups. Public transport design and services are closely related to the physical size of modern cities, the number of people living or working in them, and the distribution and organization of work and social activities. However, public transport has been restricted with the spread of the COVID-19 pandemic in Italy, since March 2020. Public transport demand collapsed, especially during the lockdown period (March-May 2020), and adverse effects were reported even in the subsequent periods. In fact, the social distancing restrictions have highlighted numerous problems with public transport systems worldwide, primarily due to two factors. The first is related to the spread of the virus via the respiratory route, which is more likely to infect in restricted areas, and the second is associated with a transport system that by definition has high occupancy rates and low spacing throughout the journey (e.g., the positioning of seats or standing places in a train or bus). Thus, the COVID-19 pandemic has substantially impacted the travel choices of users. The pandemic has also negatively affected the psychological state, generating specific problems of anxiety, fear, or stress among all population groups, even when choosing the means of transport to travel with. Given the emerging pandemic challenges, the present study examines the public transport demand characteristics during the various phases of the COVID-19 pandemic in Sicily, one of the most affected regions in Italy. The study investigates the mental state of a population sample that frequently used the local urban or regional public transport to travel to work before and during the pandemic phases in the Sicilian territory. Through the administration of an online survey, it was possible to collect sociodemographic and psychological data to understand the propensity to use public transport. A series of inferential statistical tests were applied to assess the correlation of psychological aspects (i.e., fear, anxiety, and stress) with socio-demographic variables and modal choice habits (trip frequency). Results highlight and evaluate each psychological issue among population groups and their relative role in shaping public transport-related preferences. The study highlights some proposals and their implementation strategies to prevent negative emotions and encourage public transport use in Sicily and generally.

Travel restrictions due to COVID-19 initiated a radical rethink of the urban planning process, focussing on a concept initially proposed by Carlos Moreno in 2016; the "15-Minute City" model, aiming at the improvement of quality of life by creating or rearranging cities so that residents' needs can be reached within 15-minutes on foot or by bicycle or by public transit. In continuation to a research in 2020, this paper quantifies the attractiveness of the model to residents in nine regions of Sicily in 2022. Based on statistical analysis concerning the respondents' opinion, the model examined promotes walking as an anti-stress method and improves the overall health conditions at a community level. Therefore, policy makers can revalue the existing planning process and create a blueprint for a healthier and car-free lifestyle.

Traffic congestion is one of the most significant problems in urban transportation. It has been increasing, especially in regions close to intersections. Several methods have been developed to reduce the traffic congestion. One of the analysis methods is social network analysis (SNA). This method, which has increased use in transportation, can quickly identify the most central intersections in transportation networks. Improvements to central intersections, identified in a road network structure, speed up the traffic flow across the entire network structure. In this study, the Istanbul highway transportation network has been examined and values for a series of network centrality measures have been calculated using the SNA. The accuracy and error scales of the centrality values were compared using a machine learning algorithm. The Bonacich power centrality has been the best performance. Based on the study results the most central intersections in Istanbul have been determined.

We here investigated the anti-inflammatory activity of a polymethoxylated flavone-containing fraction (PMFF) from Citrus sinensis and of a prenylflavonoid-containing one (PFF) from Humulus lupulus, either alone or in combination (MIX). To this end, an in vitro model of inflammatory bowel disease (IBD), consisting of differentiated, interleukin (IL)-1β-stimulated Caco-2 cells, was employed. We demonstrated that non-cytotoxic concentrations of either PMFF or PFF or MIX reduced nitric oxide (NO) production while PFF and MIX, but not PMFF, also inhibited prostaglandin E2 release. Coherently, MIX suppressed both inducible NO synthase and cyclooxygenase-2 over-expression besides NF-κB activation. Moreover, MIX increased nuclear factor erythroid 2–related factor 2 (Nrf2) activation, heme oxygenase-1 expression, restoring GSH and reactive oxygen and nitrogen species (RONs) levels. Remarkably, these effects with MIX were stronger than those produced by PMFF or PFF alone. Noteworthy, nobiletin (NOB) and xanthohumol (XTM), two of the most represented phytochemicals in PMFF and PFF, respectively, synergistically inhibited RONs production. Overall, our results demonstrate that MIX enhances the anti-inflammatory and anti-oxidative effects of the individual fractions in a model of IBD, via a mechanism involving modulation of NF-κB and Nrf2 signalling. Synergistic interactions between NOB and XTM emerge as a relevant aspect underlying this evidence.

Methyl gallate (MG), which is a gallotannin widely found in plants, is a polyphenol used in traditional Chinese phytotherapy to alleviate several cancer symptoms. Our studies provided evidence that MG is capable of reducing the viability of HCT116 colon cancer cells, while it was found to be ineffective on differentiated Caco-2 cells, which is a model of polarized colon cells. In the first phase of treatment, MG promoted both early ROS generation and endoplasmic reticulum (ER) stress, sustained by elevated PERK, Grp78 and CHOP expression levels, as well as an upregulation in intracellular calcium content. Such events were accompanied by an autophagic process (16–24 h), where prolonging the time (48 h) of MG exposure led to cellular homeostasis collapse and apoptotic cell death with DNA fragmentation and p53 and γH2Ax activation. Our data demonstrated that a crucial role in the MG-induced mechanism is played by p53. Its level, which increased precociously (4 h) in MG-treated cells, was tightly intertwined with oxidative injury. Indeed, the addition of N-acetylcysteine (NAC), which is a ROS scavenger, counteracted the p53 increase, as well as the MG effect on cell viability. Moreover, MG promoted p53 accumulation into the nucleus and its inhibition by pifithrin-α (PFT-α), which is a negative modulator of p53 transcriptional activity, enhanced autophagy, increased the LC3-II level and inhibited apoptotic cell death. These findings provide new clues to the potential action of MG as a possible anti-tumor phytomolecule for colon cancer treatment.

The spread of e-commerce has transformed consumer habits and distribution. There is a need to improve the location of pickup points, starting from small inland areas to areas with particular travel problems, such as the one chosen, i.e. Enna, in the centre of Sicily. The following research focuses on a two-level analysis of the accessibility perceived by users and commercial vehicles. A series of indicators were defined to evaluate the supply in terms of accessibility, the construction of isochrones, and the selection of the walking mode of travel (by demand-user). Comparing the results obtained with the values of the resident population in the different areas adjacent to the sampling points, it emerged that, at present, the 12 presented sampling points do not have an optimised spatial distribution. The overall coverage is about 60% of the population, while all sampling points are generally easily accessible. The results form the basis for more in-depth analyses to improve urban logistics and last-mile services. [ABSTRACT FROM AUTHOR]

A physiological mechanism of programmed cell death called eryptosis occurs in aged or damaged red blood cells (RBCs). Dysregulated eryptosis contributes to abnormal microcirculation and prothrombotic risk. Cigarette smoke extract (CSE) induces a p38 MAPK‐initiated, Fas‐mediated eryptosis, activating the death‐inducing signaling complex (DISC). Indicaxanthin (Ind) from cactus pear fruits, is a bioavailable dietary phytochemical in humans and it is able to incorporate into RBCs enhancing their defense against numerous stimuli. This in vitro work shows that Ind, at concentrations that mimic plasma concentrations after a fruit meal, protects erythrocytes from CSE‐induced eryptosis. CSE from commercial cigarettes was prepared in aqueous solution using an impinger air sampler and nicotine content was determined. RBCs were treated with CSE for 3 h in the absence or presence of increasing concentrations of Ind (from 1 to 5 μM). Cytofluorimetric measurements indicated that Ind reduced CSE‐induced phosphatidylserine externalization and ceramide formation in a concentration‐dependent manner. Confocal microscopy visualization and coimmunoprecipitation experiments revealed that Ind prevented both CSE‐triggered Fas aggregation and FasL/FADD/caspase 8 recruitment in the membrane, indicating inhibition of DISC assembly. Ind inhibited the phosphorylation of p38 MAPK, caspase‐8/caspase‐3 cleavage, and caspase‐3 activity induced by CSE. Finally, Ind reduced CSE‐induced ATP depletion and restored aminophospholipid translocase activity impaired by CSE treatment. In conclusion, Ind concentrations comparable to nutritionally relevant plasma concentrations, can prevent Fas‐mediated RBC death signaling induced by CSE, which suggests that dietary intake of cactus pear fruits may limit the deleterious effects of cigarette smoking. [ABSTRACT FROM AUTHOR]

From the perspective of circular economy, it is extremely useful to recycle waste products for human health applications. Among the health-beneficial properties of bioactive phyto-compounds, grape pomace represents a precious source of bioactive molecules with potential antitumor properties. Here, we describe the effects of a Sicilian grape pomace hydroalcoholic extract (HE) in colon and breast cancer cells. The characterization of HE composition revealed the predominance of anthoxanthins and phenolic acids. HE treatment was more effective in reducing the viability of colon cancer cells, while breast cancer cells appeared more resistant. Indeed, while colon cancer cells underwent apoptosis, as shown by DNA fragmentation, caspase-3 activation, and PARP1 degradation, breast cancer cells seemed to not undergo apoptosis. To elucidate the underlying mechanisms, reactive oxygen species (ROS) were evaluated. Interestingly, ROS increased in both cell lines but, while in colon cancer, cells' ROS rapidly increased and progressively diminished over time, in breast cancer, cells' ROS increase was persistent up to 24 h. This effect was correlated with the induction of pro-survival autophagy, demonstrated by autophagosomes formation, autophagic markers increase, and protection by the antioxidant NAC. The autophagy inhibitor bafilomycin A1 significantly increased the HE effects in breast cancer cells but not in colon cancer cells. Overall, our data provide evidence that HE efficacy in tumor cells depends on a balance between ROS-mediated autophagy and apoptosis. Therefore, inhibiting pro-survival autophagy may be a tool to target those cells that appear more resistant to the effect of HE. [ABSTRACT FROM AUTHOR]

Cities are often characterised by the presence of universities and by a greater number of students, often commuters, with an average age of less than 30 years. The study focused on the city of Enna (Italy), where the university students represent a significant percentage of residents and also a good rate of local travel demand. The survey campaign was conducted over a period of more than one year. A bivariate statistical method was applied highlighting significant variables regarding several features of a car sharing system. Additionally, non-parametric statistics and a before and after analysis were performed to evaluate the influence of implementation of the shared transport service. The results can also offer insights into the improvement of transport supply in urban context and the possible implementation of the co-creation actions between the companies managing the service with the end-users.

Sex hormones and genes on the sex chromosomes are not only key factors in the regulation of sexual differentiation and reproduction but they are also deeply involved in brain homeostasis. Their action is crucial for the development of the brain, which presents different characteristics depending on the sex of individuals. The role of these players in the brain is fundamental in the maintenance of brain function during adulthood as well, thus being important also with respect to age-related neurodegenerative diseases. In this review, we explore the role of biological sex in the development of the brain and analyze its impact on the predisposition toward and the progression of neurodegenerative diseases. In particular, we focus on Parkinson’s disease, a neurodegenerative disorder that has a higher incidence in the male population. We report how sex hormones and genes encoded by the sex chromosomes could protect from the disease or alternatively predispose toward its development. We finally underline the importance of considering sex when studying brain physiology and pathology in cellular and animal models in order to better understand disease etiology and develop novel tailored therapeutic strategies.