Metabolic Derangement of Essential Transition Metals and Potential Antioxidant Therapies.

Essential transition metals have key roles in oxygen transport, neurotransmitter synthesis, nucleic acid repair, cellular structure maintenance and stability, oxidative phosphorylation, and metabolism. The balance between metal deficiency and excess is typically ensured by several extracellular and intracellular mechanisms involved in uptake, distribution, and excretion. However, provoked by either intrinsic or extrinsic factors, excess iron, zinc, copper, or manganese can lead to cellular damage upon chronic or acute exposure, frequently attributed to oxidative stress. Intracellularly, mitochondria are the organelles that require the tightest control concerning reactive oxygen species production, which inevitably leaves them to be one of the most vulnerable targets of metal toxicity. Current therapies to counteract metal overload are focused on chelators, which often cause secondary effects decreasing patients' quality of life. New therapeutic options based on synthetic or natural antioxidants have proven positive effects against metal intoxication. In this review, we briefly address the cellular metabolism of transition metals, consequences of their overload, and current therapies, followed by their potential role in inducing oxidative stress and remedies thereof.

Copper impairs the intestinal barrier integrity in Wilson disease.

In Wilson disease (WD), liver copper (Cu) excess, caused by mutations in the ATPase Cu transporting beta (ATP7B), has been extensively studied. In contrast, in the gastrointestinal tract, responsible for dietary Cu uptake, ATP7B malfunction is poorly explored. We therefore investigated gut biopsies from WD patients and compared intestines from two rodent WD models and from human ATP7B knock-out intestinal cells to their respective wild-type controls. We observed gastrointestinal (GI) inflammation in patients, rats and mice lacking ATP7B. Mitochondrial alterations and increased intestinal leakage were observed in WD rats, Atp7b-/- mice and human ATP7B KO Caco-2 cells. Proteome analyses of intestinal WD homogenates revealed profound alterations of energy and lipid metabolism. The intestinal damage in WD animals and human ATP7B KO cells did not correlate with absolute Cu elevations, but likely reflects intracellular Cu mislocalization. Importantly, Cu depletion by the high-affinity Cu chelator methanobactin (MB) restored enterocyte mitochondria, epithelial integrity, and resolved gut inflammation in WD rats and human WD enterocytes, plausibly via autophagy-related mechanisms. Thus, we report here before largely unrecognized intestinal damage in WD, occurring early on and comprising metabolic and structural tissue damage, mitochondrial dysfunction, and compromised intestinal barrier integrity and inflammation, that can be resolved by high-affinity Cu chelation treatment.

A Healthy Liver Will Always Deliver: Impact Study of a Non-Alcoholic Fatty Liver Disease (NAFLD) Awareness Comic.

Based on previous work, we developed the comic "A healthy liver will always deliver!" to raise awareness about Non-Alcoholic Fatty Liver Disease (NAFLD) and promote healthy lifestyles. An online pre-post questionnaire design demonstrated an increase in health-threat beliefs regarding NAFLD among the general public, as well as response efficacy and self-efficacy beliefs, normative and control beliefs regarding the maintenance of preventive strategies involving healthy diets and active lifestyles, after interaction with the comic's narrative. This effect was more evident in women. Furthermore, although we could not perform all the ideal controls during the COVID-19 pandemic, and the online strategy attracted mostly university education-level subjects, the comic seemed relatable and engaging. However, more work will have to be performed to ensure its usefulness in terms of acquired knowledge and behavior changes, especially in at-risk segments of the population.

Deploying digitalisation and artificial intelligence in sustainable development research.

Many industrialised countries have benefited from the advent of twenty-first century technologies, especially automation, that have fundamentally changed manufacturing and industrial production processes. The next step in the evolution of automation is the development of artificial intelligence (AI), i.e. intelligence which is demonstrated by machines and systems, which cannot only perform tasks but also work synergistically with humans and nature. Intelligent systems that can see, analyse situations and respond sensitively to real-time cues, from human gestures and facial expressions to pedestrians crossing a busy street, will reshape transportation, precision agriculture, biodiversity conservation, environmental modelling, public health, construction and manufacturing, as well as initiatives designed to promote prosperity on Earth. This paper explores the connections between AI systems and sustainable development (SD) research. By means of a literature review, world survey, and case studies, ways in which AI can support research on SD and, inter alia, contribute to a more sustainable and equitable world, are identified.

Towards symbiotic approaches between universities, sustainable development, and cities.

Universities are key actors and play a central role in the cities which host them, either as employers, consumers or simply as a magnet to young people and cultural activities. They can be also influencers and supporters of cities in the field of sustainable development. Through an exploratory method and aiming to explore the efforts deployed to foster closer links between universities, sustainable development, and cities and address a literature gap in this regard, this study considers the contribution of universities to sustainable development at the city level. Based on some of the ongoing initiatives worldwide and an international online survey documenting measures undertaken, this study translates the commitment to pursuing sustainable development within cities, with responses from a sample of 45 countries. This study lists some items which may help foster more symbiotic relations between cities and universities. The findings of this study may be used as baselines for strengthening the connections between universities and cities in addressing the sustainable development challenges, as demonstrated through the responses obtained. Accordingly, some suggested actions involving cooperation may include increased communication with city stakeholders and the undertaking of joint initiatives and projects, taking advantage of the ongoing sustainable development challenges worldwide.

The use of comics to promote health awareness: A template using nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) constitutes a major threat to public health systems worldwide on account of its widespread prevalence and increasing incidence. More effective tools to raise awareness and increase health communication are therefore needed. Comics may constitute an effective language for this purpose, given the permanence, adaptability and ability of this form of communication to convey complex information, using both visual components and the creation of narrative involvement, thus promoting both awareness and health-conscious behaviours. Importantly, this process requires careful preparation in terms of selecting both the key biomedical concepts to be conveyed, as well as a graphical style and appropriate characters and a narrative arc with which a target audience can identify with. Here we provide a brief introduction to the use of comics in health communication and propose a possible roadmap for the development of comic-based tools for diverse conditions, using the context of NAFLD.

Mushrooms on the plate: Trends towards NAFLD treatment, health improvement and sustainable diets.

Non-alcoholic fatty liver disease (NAFLD) is a most important cause of liver disease. Similar to other non-communicable diseases (NCD), such as obesity and type II diabetes mellitus, NAFLD can strongly affected by diet. Diet-related NCD and malnutrition are rising in all regions being a major cause of the global health, economic and environmental burdens. Mushrooms, important dietary components since the hunter-gathering communities, have increasingly gained momentum in biomedical research and therapeutics due to their interplay in metabolism traits. We emphasize here the beneficial effects of mushroom-enriched diets on the homeostasis of lipid and sugar metabolism, including their modulation, but also interfering with insulin metabolism, gut microbiota, inflammation, oxidative stress and autophagy. In this review, we describe the cellular and molecular mechanisms at the gut-liver axis and the liver-white adipose tissue (WAT) axis, that plausibly cause such positive modulation, and discuss the potential of mushroom-enriched diets to prevent or ameliorate NAFLD and related NCD, also within the shift needed towards healthy sustainable diets.

Unhealthy lifestyles, environment, well-being and health capability in rural neighbourhoods: a community-based cross-sectional study.

BACKGROUND: Non-communicable diseases are a leading cause of health loss worldwide, in part due to unhealthy lifestyles. Metabolic-based diseases are rising with an unhealthy body-mass index (BMI) in rural areas as the main risk factor in adults, which may be amplified by wider determinants of health. Changes in rural environments reflect the need of better understanding the factors affecting the self-ability for making balanced decisions. We assessed whether unhealthy lifestyles and environment in rural neighbourhoods are reflected into metabolic risks and health capability. METHODS: We conducted a community-based cross-sectional study in 15 Portuguese rural neighbourhoods to describe individuals' health functioning condition and to characterize the community environment. We followed a qualitatively driven mixed-method design to gather information about evidence-based data, lifestyles and neighbourhood satisfaction (incorporated in eVida technology), within a random sample of 270 individuals, and in-depth interviews to 107 individuals, to uncover whether environment influence the ability for improving or pursuing heath and well-being. RESULTS: Men showed to have a 75% higher probability of being overweight than women (p-value = 0.0954); and the reporting of health loss risks was higher in women (RR: 1.48; p-value = 0.122), individuals with larger waist circumference (RR: 2.21; IC: 1.19; 4.27), overweight and obesity (RR: 1.38; p-value = 0.293) and aged over 75 years (RR: 1.78; p-value = 0.235; when compared with participants under 40 years old). Metabolic risks were more associated to BMI and physical activity than diet (or sleeping habits). Overall, metabolic risk linked to BMI was higher in small villages than in municipalities. Seven dimensions, economic development, built (and natural) environment, social network, health care, demography, active lifestyles, and mobility, reflected the self-perceptions in place affecting the individual ability to make healthy choices. Qualitative data exposed asymmetries in surrounding environments among neighbourhoods and uncovered the natural environment and natural resources specifies as the main value of rural well-being. CONCLUSIONS: Metabolic risk factors reflect unhealthy lifestyles and can be associated with environment contextual-dependent circumstances. People-centred approaches highlight wider socioeconomic and (natural) environmental determinants reflecting health needs, health expectations and health capability. Our community-based program and cross-disciplinary research provides insights that may improve health-promoting changes in rural neighbourhoods.

COVID-19: the impact of a global crisis on sustainable development research.

The crisis caused by COVID-19 has affected research in a variety of ways. As far as research on sustainable development is concerned, the lockdown has significantly disrupted the usual communication channels and, among other things, has led to the cancellation of meetings and long-planned events. It has also led to delay in the delivery of research projects. There is a gap in the literature in regards to how a global crisis influences sustainability research. Therefore, this ground-breaking paper undertakes an analysis of the extent to which COVID-19 as a whole, and the lockdown in particular, has influenced sustainability research, and it outlines the solutions pursued by researchers around the world to overcome the many challenges they have experienced. This paper also outlines some measures that may be implemented in the future to take more advantage of existing technologies that support research on sustainable development.

Insights from qualitative research on NAFLD awareness with a cohort of T2DM patients: time to go public with insulin resistance?

BACKGROUND: It is estimated that around 70% of Type 2 Diabetes Mellitus patients (T2DM) have Non-Alcoholic Fatty Liver Disease (NAFLD). Awareness and education are amongst the major shortcomings of the public health response to the increasing threat of NAFLD. Characterizing the specific NAFLD-related information needs of particular high-risk metabolic communities, for instance, T2DM patients, might aid in the development of evidence-based health promotion strategies, ultimately promoting NAFLD-awareness, treatment adherence and therapeutic success rates. METHODS: Semi-structured interviews with T2DM patients were conducted to gain insight into their awareness of NAFLD, including its relationship with insulin resistance and T2DM. RESULTS: Awareness of NAFLD as a disease entity, as well as its progression to end-stage liver disease or its relationship with other metabolic conditions, including insulin resistance and T2DM was low. Surveillance behaviours were also suboptimal and perceptions on the self-management knowledge and praxis regarding lifestyle intervention components of T2DM treatment seemed detached from those of NAFLD. CONCLUSIONS: Our findings could inform the integration of NAFLD-related content in T2DM health promotion strategies. Rising awareness on NAFLD progression and its relationship with T2DM using culturally and community-relevant constructs might facilitate the development of primary and secondary prevention programmes to promote the adherence to lifestyle interventions by influencing NAFLD threat perceptions.

Antioxidant Versus Pro-Apoptotic Effects of Mushroom-Enriched Diets on Mitochondria in Liver Disease.

Mitochondria play a central role in non-alcoholic fatty liver disease (NAFLD) progression and in the control of cell death signalling during the progression to hepatocellular carcinoma (HCC). Associated with the metabolic syndrome, NAFLD is mostly driven by insulin-resistant white adipose tissue lipolysis that results in an increased hepatic fatty acid influx and the ectopic accumulation of fat in the liver. Upregulation of beta-oxidation as one compensatory mechanism leads to an increase in mitochondrial tricarboxylic acid cycle flux and ATP generation. The progression of NAFLD is associated with alterations in the mitochondrial molecular composition and respiratory capacity, which increases their vulnerability to different stressors, including calcium and pro-inflammatory molecules, which result in an increased generation of reactive oxygen species (ROS) that, altogether, may ultimately lead to mitochondrial dysfunction. This may activate further pro-inflammatory pathways involved in the progression from steatosis to steatohepatitis (NASH). Mushroom-enriched diets, or the administration of their isolated bioactive compounds, have been shown to display beneficial effects on insulin resistance, hepatic steatosis, oxidative stress, and inflammation by regulating nutrient uptake and lipid metabolism as well as modulating the antioxidant activity of the cell. In addition, the gut microbiota has also been described to be modulated by mushroom bioactive molecules, with implications in reducing liver inflammation during NAFLD progression. Dietary mushroom extracts have been reported to have anti-tumorigenic properties and to induce cell-death via the mitochondrial apoptosis pathway. This calls for particular attention to the potential therapeutic properties of these natural compounds which may push the development of novel pharmacological options to treat NASH and HCC. We here review the diverse effects of mushroom-enriched diets in liver disease, emphasizing those effects that are dependent on mitochondria.

Use of lignocellulosic wastes of pecan (Carya illinoinensis) in the cultivation of Ganoderma lucidum / Utilización de residuos lignocelulósicos de la pacana (Carya illinoinensis) para el cultivo del hongo Ganoderma lucidum

Background: The wastes of pecan nut (Carya illinoinensis (Wangenh.) K. Koch) production are increasing worldwide and have high concentrations of tannins and phenols. Aims: To study the biodegradation of lignocellulosic wastes of pecan used as solid substrate for the cultivation of the white-rot fungus Ganoderma lucidum (Curtis) P. Karst. Methods: Six formulations of pecan wastes were used as solid substrate: pecan shells (PS100), pecan pericarp (PP100), pecan wood-chips (PB100), and the combinations PS50+PP50, PB50+PS50 and PB50+PP50. The substrates were inoculated with a wild strain of G. lucidum collected in the Iberian Peninsula. The biodegradation capability of G. lucidum was estimated by using the mycelial growth rate, the biological efficiency, the production and the dry biological efficiency. Results: Notably, all solid substrates were suitable for G. lucidum growth and mushroom yield. The best performance in mushroom yield was obtained with PB100 (55.4% BE), followed by PB50+PP50 (31.7% BE) and PB50+PS50 (25.4% BE). The mushroom yield in the substrates containing pecan wood-chips (PB) was significantly higher. Conclusions: Our study is leading the way in attempting the cultivation of G. lucidum on lignocellulosic pecan waste. These results show an environmentally friendly alternative that increases the benefits for the global pecan industry, especially in rural areas, and transforms biomass into mushrooms with nutraceutical properties and biotechnological applications

Antecedentes: Los residuos de la producción de pacana (Carya illinoinensis [Wangenh.] K. Koch) se distribuyen por todo el mundo y poseen elevadas concentraciones de taninos y fenoles. Objetivos: Estudiar la biodegradación de los residuos lignocelulósicos de la pacana usados como sustrato sólido para el cultivo de Ganoderma lucidum (Curtis) P. Karst. Métodos: Se utilizaron seis formulaciones de sustratos sólidos a partir de los residuos: cáscara de la nuez (PS100), pericarpio de la nuez (PP100), astillas de ramas de poda (PB100) y las combinaciones PS50+PP50, PB50+PS50 y PB50+PP50. Los sustratos se inocularon con las hifas de una cepa silvestre de G. lucidum procedente de la península ibérica. La capacidad de biodegradación de G. lucidum se estimó mediante el ratio de crecimiento micelial, la eficiencia biológica, la producción de carpóforos y la eficiencia biológica en seco. Resultados: Notablemente, todos los sustratos sólidos utilizados resultaron adecuados para ser colonizados por G. lucidum y producir carpóforos. Los mejores rendimientos en cultivo se obtuvieron con la formulación PB100 (55,4% BE), seguida por PB50+PP50 (31,7% BE) y PB50+PS50 (25,4% BE). La producción de carpóforos en sustratos con astillas de ramas del árbol (PB) fue considerablemente más elevada que en aquellos que no contenían este residuo. Conclusiones: Este estudio muestra la posibilidad de cultivar G. lucidum sobre residuos lignocelulósicos de pacana. Los resultados obtenidos sugieren una alternativa respetuosa con el medio ambiente para el incremento de los beneficios en la industria de la pacana a nivel internacional, especialmente en zonas rurales, al convertir biomasa en la producción de un hongo de interés nutracéutico y con aplicaciones biotecnológicas

Use of lignocellulosic wastes of pecan (Carya illinoinensis) in the cultivation of Ganoderma lucidum.

BACKGROUND: The wastes of pecan nut (Carya illinoinensis (Wangenh.) K. Koch) production are increasing worldwide and have high concentrations of tannins and phenols. AIMS: To study the biodegradation of lignocellulosic wastes of pecan used as solid substrate for the cultivation of the white-rot fungus Ganoderma lucidum (Curtis) P. Karst. METHODS: Six formulations of pecan wastes were used as solid substrate: pecan shells (PS100), pecan pericarp (PP100), pecan wood-chips (PB100), and the combinations PS50+PP50, PB50+PS50 and PB50+PP50. The substrates were inoculated with a wild strain of G. lucidum collected in the Iberian Peninsula. The biodegradation capability of G. lucidum was estimated by using the mycelial growth rate, the biological efficiency, the production and the dry biological efficiency. RESULTS: Notably, all solid substrates were suitable for G. lucidum growth and mushroom yield. The best performance in mushroom yield was obtained with PB100 (55.4% BE), followed by PB50+PP50 (31.7% BE) and PB50+PS50 (25.4% BE). The mushroom yield in the substrates containing pecan wood-chips (PB) was significantly higher. CONCLUSIONS: Our study is leading the way in attempting the cultivation of G. lucidum on lignocellulosic pecan waste. These results show an environmentally friendly alternative that increases the benefits for the global pecan industry, especially in rural areas, and transforms biomass into mushrooms with nutraceutical properties and biotechnological applications.

Development, optimization and application of an analytical methodology by ultra performance liquid chromatography-tandem mass spectrometry for determination of amanitins in urine and liver samples.

Amanitins, highly toxic cyclopeptides isolated from various Amanita species, are the most potent poisons accounting for the hazardous effects on intestinal epithelium cells and hepatocytes, and probably the sole cause of fatal human poisoning. The present study was focused on the development, optimization and application of an analytical methodology by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), following urine and liver sample preparation by protein precipitation with organic solvents, and solid phase extraction (SPE) procedure, for the determination of the amatoxins, α- and ß-amanitin. Linearity, detection and quantification limits, selectivity, sensitivity, intra and inter-assay precision and recovery were studied, in order to guarantee reliability in the analytical results. The developed method proved to be specific and selective, with LOD (Limit of Detection) values for α- and ß-amanitin of 0.22 and 0.20 ng mL(-1) in urine and 10.9 and 9.7 ng g(-1) in liver, respectively. LOQ (Limit of Quantification) values ranged from 0.46 to 0.57 ng mL(-1) in urine and 12.3-14.7 ng g(-1) in tissue, for both amanitins. Linearity, in the range of 10.0-200.0 ng mL(-1) or ng g(-1), shows that coefficients of correlation were greater than 0.997 for α-amanitin and 0.993 for ß-amanitin. Precision was checked at three levels during three consecutive days with intra-day and inter-day coefficients of variation not greater than 15.2%. The extraction recovery presents good results for the concentrations analyzed, with values ranging from 90.2 to 112.9% for both matrices. Thus, the proposed analytical method is innovative, presents a high potential in the identification, detection and determination of α- and ß-amanitins in urine and tissue samples, as well as in other biological samples, such as kidney and mushrooms.

Land use practices and ectomycorrhizal fungal communities from oak woodlands dominated by Quercus suber L. considering drought scenarios.

Oak woodlands in the Mediterranean basin have been traditionally converted into agro-silvo-pastoral systems and exemplified sustainable land use in Europe. In Portugal, in line with the trend of other European countries, profound changes in management options during the twentieth century have led to landscape simplification. Landscapes are dynamic and the knowledge of future management planning combining biological conservation and soil productivity is needed, especially under the actual scenarios of drought and increasing evidence of heavy oak mortality. We examined the ectomycorrhizal (ECM) fungal community associated with cork oak in managed oak woodlands (called montado) under different land use practices, during summer. ECM fungal richness and abundance were assessed in 15 stands established in nine montados located in the Alentejo region (southern Portugal), using morphotyping and ITS rDNA analysis. Parameters related to the montados landscape characteristics, land use history over the last 25 years, climatic and edaphic conditions were taken into account. Fifty-five ECM fungal taxa corresponding to the most abundant fungal symbionts were distinguished on cork oak roots. Cenococcum geophilum and the families Russulaceae and Thelephoraceae explained 56% of the whole ECM fungal community; other groups were represented among the community: Cortinariaceae, Boletaceae, Amanita, Genea, Pisolithus, Scleroderma, and Tuber. There were pronounced differences in ECM fungal community structure among the 15 montados stands: C. geophilum was the only species common to all stands, tomentelloid and russuloid species were detected in 87-93% of the stands, Cortinariaceae was detected in 60% of the stands, and the other groups were more unequally distributed. Ordination analysis revealed that ECM fungal richness was positively correlated with the silvo-pastoral exploitation regime and low mortality of cork oak, while ECM fungal abundance was positively correlated with extensive agro-silvo-pastoral exploitation under a traditional 9-year rotation cultivation system and recent soil tillage. The effects of land use on the ECM fungal community and its implications in different scenarios of landscape management options, oak mortality, and global warming are discussed.