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Cutaneous melanoma (CM) is the most lethal form of skin cancer if it becomes metastatic, where treatment options and survival chances decrease dramatically. Immunotherapy treatments based on the immunologic checkpoint inhibitors programmed death cell protein 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) constituted a main breakthrough in the treatment of metastatic CM, particularly for the achievement of long-term benefits. Even though it is a very promising therapy, resistance to primary immune checkpoint blockade (ICB) arises in about 70% of CM patients treated with a CTLA-4 inhibitor, and 40–65% of CM patients administered with a PD-1-targeting treatment. Some long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) are implicated in triggering pro- and anti-tumorigenic responses to various cancer treatments. The relationship between lncRNAs, circRNAs and ICB immunotherapy has not been explored in cutaneous metastatic melanoma (CMM). The aim of this pilot study is to evaluate the potential role of circRNA and lncRNA expression variability as pre-treatment predictor of the clinical response to immunotherapy in CMM patients. RNA-seq from 12 formalin-fixed paraffin-embedded (FFPE) samples from the metastatic biopsies of CMM patients treated with nivolumab was used to identify response-associated transcripts. Our findings indicate that specific lncRNAs and circRNAs, probably acting as competitive endogenous RNAs (ceRNAs), are involved in the regulatory networks of the immune response against metastatic melanoma that these patients have under treatment with nivolumab. Moreover, we established a risk score that yields predictions of the overall survival (OS) and progression-free survival (PFS) of CMM patients with high accuracy. This proof-of-principle work provides a possible insight into the function of ceRNAs, contributing to efforts to decipher the complex molecular mechanisms of ICB cancer treatment response.

Alternaria alternata is a saprophytic mold whose spores are disseminated in warm dry air, the typical weather of the Mediterranean climate region (from 30° to 45°), with a peak during the late summer and early autumn. Alternaria spores are known to be biological contaminants and a potent source of aeroallergens. One consequence of human exposure to Alternaria is an increased risk of developing asthma, with Alt a 1 as its main elicitor and a marker of primary sensitization. Although the action mechanism needs further investigation, a key role of the epithelium in cytokine production, TLR-activated alveolar macrophages and innate lymphoid cells in the adaptive response was demonstrated. Furthermore, sensitization to A. alternata seems to be a trigger for the development of co-sensitization to other allergen sources and may act as an exacerbator of symptoms and an elicitor of food allergies. The prevalence of A. alternata allergy is increasing and has led to expanding research on the role of this fungal species in the induction of IgE-mediated respiratory diseases. Indeed, recent research has allowed new perspectives to be considered in the assessment of exposure and diagnosis of fungi-induced allergies, although more studies are needed for the standardization of immunotherapy formulations.

Cherry is a fruit which contains elevated amounts of antioxidant compounds, such as anthocyanins, pigments, and vitamins. Furthermore, it possesses high water, sugar, mineral, and indolamine contents. The general objective of this study was to characterise a cherry-based fermented beverage (the ‘sweetheart’ variety) and analyse the effects of its ingestion on (i) circulating serum levels of melatonin and serotonin, (ii) inflammatory response, and iii) serum total antioxidant capacity in rats (Rattus norvegicus). For cherry-based fermented beverage manufacturing, the cherries were washed, the stems and woody endocarps were removed, and ascorbic acid was added (to avoid enzymatic browning). After the homogenisation of the cherry fruit, lactic acid bacteria were inoculated, and the fermentation process was conducted for 36 h. The main bioactive compounds in the cherry beverage were characterised, as well as their total antioxidant capacity. Moreover, an in vivo assay was developed, in which rats ingested the fermented beverage ad libitum for seven days. The inflammatory mediators, the total antioxidant capacity, and the serum levels of melatonin and serotonin were measured. Based on these results, the intake of the cherry-based fermented beverage assayed in this study increased the total antioxidant status of rats, elevated the melatonin and serotonin levels in the serum, and improved the regulation of the inflammatory systemic processes.

The interaction between the plant lipid transfer protein Pru p 3 and phytosphingosine was assessed using an atomic force microscope. Phytosphingosine was covalently immobilized on DeepTipTM probes and Pru p 3 on MicroDeckTM functionalized substrates. Single-molecular interaction events between both molecules were retrieved and classified and the distribution for each one of the identified types was calculated. A success rate of over 70% was found by comparing the number of specific Pru p 3-phytosphingosine interaction events with the total number of recorded curves. The analysis of the distribution established among the various types of curves was further pursued to distinguish between those curves that can mainly be used for assessing the recognition between phytosphingosine (sensor molecule) and Pru p 3 (target molecule) in the context of affinity atomic force microscopy, and those that entail details of the interaction and might be employed in the context of force spectroscopy. The successful application of these functionalized probes and substrates to the characterization of the low-intensity hydrophobic interaction characteristic of this system is a clear indication of the potential of exploiting this approach with an extremely wide range of different biological molecules of interest. The possibility of characterizing molecular assembly events with single-molecule resolution offers an advantageous procedure to plough into the field of molecular biomimetics.

Emotional intelligence is a determinant factor in sports performance. The present study analysed differences in total emotional intelligence and its four dimensions in 2166 Spanish athletes (25.20 ± 10.17 years) from eight sports (volleyball, track and field, shooting, football, basketball, handball, gymnastics, and judo). A total of 1200 men and 966 women answered anonymously using a Google Forms questionnaire sent via WhatsApp about demographics and psychological variables. A Pearson correlation was conducted to assess the age–emotional intelligence relationship. An independent T-test and One-Way ANOVA were carried out to check for age differences between biological sex and sport and a One-Way ANCOVA to determine differences between sports controlled by age. Age differences were observed by sex and sport (p < 0.001). An association was found between age and emotional intelligence dimensions (p < 0.001), except for other’s emotional appraisal (p > 0.05). Judo was the sport with the highest levels of regulation of emotions, other’s emotional appraisal, use of emotion, and total emotional intelligence (p < 0.05). Generally, emotional intelligence was found to be more developed in individual sports than in team sports, except football. Consequently, psychological skills like emotional intelligence could be critical to achieving high performance, depending on the sport.

Fibromyalgia syndrome (FMS) is a chronic widespread pain syndrome that is accompanied by fatigue, sleep disturbances, anxiety, depression, lack of concentration, and neurocognitive impairment. As the currently available drugs are not completely successful against these symptoms and frequently have several side effects, many scientists have taken on the task of looking for nonpharmacological remedies. Many of the FMS-related symptoms have been suggested to be associated with an altered pattern of endogenous melatonin. Melatonin is involved in the regulation of several physiological processes, including circadian rhythms, pain, mood, and oxidative as well as immunomodulatory balance. Preliminary clinical studies have propounded that the administration of different doses of melatonin to patients with FMS can reduce pain levels and ameliorate mood and sleep disturbances. Moreover, the total antioxidant capacity, 6-sulfatoxymelatonin and urinary cortisol levels, and other biological parameters improve after the ingestion of melatonin. Recent investigations have proposed a pathophysiological relationship between mitochondrial dysfunction, oxidative stress, and FMS by looking at certain proteins involved in mitochondrial homeostasis according to the etiopathogenesis of this syndrome. These improvements exert positive effects on the quality of life of FMS patients, suggesting that the use of melatonin as a coadjuvant may be a successful strategy for the management of this syndrome.

Plant-based extracts possess biological potential due to their high content of phytochemicals. Nevertheless, photosynthetic pigments (e.g., chlorophylls) that are also present in plant extracts could produce undesirable pro-oxidant activity that might cause a negative impact on their eventual application. Herein, the phenolic content of olive leaf (OLE) and green tea (GTE) extracts was assayed, and their antioxidant and anticancer activities were evaluated before and after the removal of chlorophylls. Regarding phenolic content, OLE was rich in hydroxytyrosol, tyrosol as well as oleuropein, whereas the main compounds present in GTE were gallocatechin, epigallocatechin (EGC), epigallocatechin gallate (EGCG), gallocatechin gallate, and caffeine. Interestingly, fresh extracts’ antioxidant ability was dependent on phenolic compounds; however, the elimination of chlorophyll compounds did not modify the antioxidant activity of extracts. In addition, both OLE and GTE had high cytotoxicity against HL-60 leukemic cell line. Of note, the removal of chlorophyll pigments remarkably reduced the cytotoxic effect in both cases. Therefore, our findings emphasize the remarkable antioxidant and anticancer potential of OLE and GTE and suggest that chlorophylls are of paramount importance for the tumor-killing ability of such plant-derived extracts.

Infertility is an increasing global public health concern with socio-psychological implications for affected couples. Remarkable advances in reproductive medicine have led to successful treatments such as assisted reproductive techniques (ART). However, the search for new therapeutic tools to improve ART success rates has become a research hotspot. In the last few years, pineal indolamine melatonin has been investigated for its powerful antioxidant properties and its role in reproductive physiology. It is considered a promising therapeutical agent to counteract the detrimental effects associated with oxidative stress in fertility treatments. The aim of the present narrative review was to summarize the current state of the art on the importance of melatonin in reproductive physiology and to provide a critical evaluation of the data available encompassing basic, translational and clinical studies on its potential use in ART to improve fertility success rates.

In the present work, highly multiplexed diagnostic KITs based on an Interferometric Optical Detection Method (IODM) were developed to evaluate six Coronavirus Disease 2019 (COVID-19)-related biomarkers. These biomarkers of COVID-19 were evaluated in 74 serum samples from severe, moderate, and mild patients with positive polymerase chain reaction (PCR), collected at the end of March 2020 in the Hospital Clínico San Carlos, in Madrid (Spain). The developed multiplexed diagnostic KITs were biofunctionalized to simultaneously measure different types of specific biomarkers involved in COVID-19. Thus, the serum samples were investigated by measuring the total specific Immunoglobulins (sIgT), specific Immunoglobulins G (sIgG), specific Immunoglobulins M (sIgM), specific Immunoglobulins A (sIgA), all of them against SARS-CoV-2, together with two biomarkers involved in inflammatory disorders, Ferritin (FER) and C Reactive Protein (CRP). To assess the results, a Multiple Linear Regression Model (MLRM) was carried out to study the influence of IgGs, IgMs, IgAs, FER, and CRP against the total sIgTs in these serum samples with a goodness of fit of 73.01% (Adjusted R-Squared).

Phenolic compounds are secondary metabolites widely spread throughout the plant kingdom that can be categorized as flavonoids and non-flavonoids. Interest in phenolic compounds has dramatically increased during the last decade due to their biological effects and promising therapeutic applications. In this review, we discuss the importance of phenolic compounds’ bioavailability to accomplish their physiological functions, and highlight main factors affecting such parameter throughout metabolism of phenolics, from absorption to excretion. Besides, we give an updated overview of the health benefits of phenolic compounds, which are mainly linked to both their direct (e.g., free-radical scavenging ability) and indirect (e.g., by stimulating activity of antioxidant enzymes) antioxidant properties. Such antioxidant actions reportedly help them to prevent chronic and oxidative stress-related disorders such as cancer, cardiovascular and neurodegenerative diseases, among others. Last, we comment on development of cutting-edge delivery systems intended to improve bioavailability and enhance stability of phenolic compounds in the human body.

CD1 molecules present lipid antigens to T-cells in early stages of immune responses. Whereas CD1‒lipid‒T-cell receptors interactions are reasonably understood, molecular details on initial trafficking and loading of lipids onto CD1 proteins are less complete. We present a molecular dynamics (MD) study of human CD1d, the isotype that activates iNKT cells. MD simulations and calculations of properties and Poisson-Boltzmann electrostatic potentials were used to explore the dynamics of the antigen-binding domain of the apo-form, CD1d complexes with three lipid–antigens that activate iNKT cells and CD1d complex with GM2AP, a protein that assists lipid loading onto CD1 molecules in endosomes/lysosomes. The study was done at pH 7 and 4.5, values representative of strongly acidic environments in endosomal compartments. Our findings revealed dynamic features of the entrance to the hydrophobic channels of CD1d modulated by two α helices with sensitivity to the type of lipid. We also found lipid- and pH-dependent dynamic changes in three exposed tryptophans unique to CD1d among the five human CD1 isotypes. On the basis of modelled structures, our data also revealed external effects produced by the helper protein GM2AP only when it interacts in its open form, thus suggesting that the own assistant protein also adapts conformation to association with CD1d.

Simultaneous modulation of several targets or pathological events with a key pathogenic role isa promising strategy to tackle thus far difficult-to-cure or incurable multifactorial diseases [...]

Saposins are small proteins implicated in trafficking and loading of lipids onto Cluster of Differentiation 1 (CD1) receptor proteins that in turn present lipid antigens to T cells and a variety of T-cell receptors, thus playing a crucial role in innate and adaptive immune responses in humans. Despite their low sequence identity, the four types of human saposins share a similar folding pattern consisting of four helices linked by three conserved disulfide bridges. However, their lipid-binding abilities as well as their activities in extracting, transporting and loading onto CD1 molecules a variety of sphingo- and phospholipids in biological membranes display two striking characteristics: a strong pH-dependence and a structural change between a compact, closed conformation and an open conformation. In this work, we present a comparative computational study of structural, electrostatic, and dynamic features of human saposins based upon their available experimental structures. By means of structural alignments, surface analyses, calculation of pH-dependent protonation states, Poisson-Boltzmann electrostatic potentials, and molecular dynamics simulations at three pH values representative of biological media where saposins fulfill their function, our results shed light into their intrinsic features. The similarities and differences in this class of proteins depend on tiny variations of local structural details that allow saposins to be key players in triggering responses in the human immune system.