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Diamine oxidase (DAO) supplements have gained increasing attention in recent years due to their potential to support DAO deficiency, histamine intolerance and related symptoms. However, choosing a reliable and trustworthy DAO supplement can be a challenging task for patients and Healthcare practitioners. One of the main concerns is the lack of regulatory oversight on dietary supplements, which may result in misleading or incomplete labelling, incorrect dosages, and inadequate quality control. Such situations may lead to patients consuming supplements with insufficient amounts of active enzyme or with questionable purity, potentially resulting in undesired health outcomes. Thus, we tested the DAO activity of a variety of already in-the-market supplements and compared them with one another and against the specified activity, if any, by the manufacturer. Our results show a great discrepancy in most of the products and significant differences in DAO activity between different manufacturers.

This study evaluated the anti-inflammatory effects, protection of gut barrier integrity, and stimulation of phagocytosis in peripheral cells of a nutritional supplement based on a synergistic combination of yeast-based ingredients with a unique 1,3/1,6-glucan complex and a consortium of postbiotic Saccharomyces cerevisiae rich in selenium and zinc. The anti-inflammatory effect in Caco-2 cells in the presence and absence of a pro-inflammatory challenge (tumour necrosis factor alpha [TNF-α]/interferon gamma [IFN-ɣ]) showed statistically significant reductions of IFN-ɣ induced protein-10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1) levels vs. controls (p < 0.001). Disruption of the gut integrity in the presence or absence of Escherichia coli (ETEC H10407) showed transepithelial electrical resistance (TEER) values higher in the ABB C1® group after 6 hours of testing. Spontaneous build-up of the gut epithelium monolayer over 22 days was also greater in the ABB C1® condition vs. a negative control. ABB C1® showed a significantly higher capacity to stimulate phagocytosis as compared with controls of algae β-1,3-glucan and yeast β-1,3/1,6 glucan (p < 0.001). This study supports the mechanism of action by which ABB C1® may improve the immune response and be useful to prevent infection and allergy in clinical practice.

Background: Non-suicidal self-harming behavior is increasingly prevalent in Danish society. In somatic Emergency Departments (ED), they constitute 12,100 contacts a year. This behavior creates conflicts and (sometimes) the use of coercive measures. Experiences and research-based knowledge show treatment in the ED is challenging. Patients experience a misunderstood treatment, and nurses articulate negative attitudes such as antipathy and a stigmatizing behavior. Existing studies focus on the therapeutical treatment, such as dialectical behavior therapy where the patient is able to participate in the treatment. However, the nurses lack the knowledge of how to support these patients during a psychological crisis.Mental Health Services Region Zealand, developed a digital solution in the form of a mobile application ‘SAFE app’. The app was co-created with a multidisciplinary psychiatric team and users with lived experiences (patients and relatives). The aim of the app was to provide better and more efficient care and support. SAFE app consists of 36 calming methods. Feedback from staff members and users (relatives and people with lived experiences) was promising. However it was difficult to use the app in critical situations, where patients enter the ED.Hypothesis: When people who self-harm can use SAFE app and they can take care of their immediate needs, they will experience the treatment in ED helpful.Aims: To explore how SAFE app, a digital solution can support Treatment As Usual (TAU) in ED when people are seeking help after an episode of non-suicidal self-harm. Method: A qualitative interview study with a hermeneutical approach (Hans Georg Gadamer)was undertaken from March - April 2021. It involved two emergency departments and included all participants (n=26) who were seeking help after an episode of non-suicidal self-harm. Firstly, all participants were informed and guided in the use of SAFE app. Hereafter in-depth telephone interviews were conducted and analyzed.Results: When people enter the ED after an episode of self-harm, they described how the relationship with the professional was problematic, such as a lack of communication with the nurses, a lack of trust in the system and misunderstandings. They experienced conflict full encounters, such as when nurses possessed authoritarian behavior and they acted as guards. The SAFE app could mitigate these experiences as they found the calming methods helpful and distracting. SAFE app was perceived as a positive and caregiving supplement in TAU, which could establish a relationship with the nurses. However, they found the app to be too feminine. Discussion: The area of research is relatively young. People who engage in self-harm, experience different reasons for hurting themselves. The SAFE app can provide learning for friends, family, health-care professionals and others. The interventions must be tested in a broader population.Conclusion: Findings from this study suggest that digital solutions can supplement TAU for people with non-suicidal self-harming behavior in ED. Digital solutions can potentially improve the experiences of hospitalization, particularly in the creation of relations to the nurses. Implications for practice: Future implementation of the SAFE app will potentially reduce conflicts with nurses and provide patient-experienced quality of care.

O6-alkylguanine-DNA-alkyltransferase (hAGT) activity provides resistance to cancer chemotherapeutic agents and its inhibition enhances chemotherapy. We herein present the development of a novel fluorescence assay for the detection of hAGT activity. We designed a dsDNA sequence containing a fluorophore-quencher pair, where the fluorophore was attached to an O6-benzylguanine. This precursor was synthesized using the Mitsunobu reaction to introduce the benzyl group. The alkyl-fluorophore group is transferred to the active site during the dealkylation, producing an increase in fluorescence which is correlated to hAGT activity. This assay can be used for the evaluation of potential inhibitors of hAGT in a straightforward manner., The Communities MULTIFUN (contract NMP4-LA-2011-262943), Spanish Healthcare Research Fund (grant PI06/1250) and Spanish Ministry of Economy and Competitiveness (grants CTQ-2010-20541-C03-03 and CTQ2014-52588-R) are acknowledged for financialsupport. M.T. was supported by a pre-doctoral fellowship (FPI) from MINECO. C.F is grateful to TV3 Marato 2012 for a research contract.

DNA's remarkable molecular recognition properties, flexibility, and structural features make it one of the most promising scaffolds to design a variety of nanostructures. During recent decades, two major methods have been developed for the construction of DNA nanomaterials in a programmable way; both generate nanostructures in one, two, and three dimensions. The tile-based assembly process is a useful tool to construct large and simple structures; the DNA origami method is suitable for the production of smaller, more sophisticated and well-defined structures. Proteins, nanoparticles and other functional elements have been specifically positioned into designed patterns on these structures. They can also act as templates to study chemical reactions, help in the structural determination of proteins, and be used as platform for genomic and drug delivery applications. In this review we examine recent progresses towards the potential use of DNA nanostructures in molecular and cellular biology.

The endonucleolytic activity of human apurinic/apyrimidinic endonuclease (AP endo, Ape1) is a major factor in maintaining the integrity of the genome. Conversely, as an undesired effect, Ape1 overexpression has been linked to resistance to radio- and chemotherapeutic treatments in several human tumors. Inhibition of Ape1 using siRNA or the expression of a dominant negative form of the protein has been shown to sensitize cells to DNA-damaging agents, including various chemotherapeutic agents. Therefore, inhibition of the enzymatic activity of Ape1 might result in a potent antitumor therapy. A number of small molecules have been described as Ape1 inhibitors; however, those compounds are in the early stages of development. Herein we report the identification of new compounds as potential Ape1 inhibitors through a docking-based virtual screening technique. Some of the compounds identified have invitro activities in the low-to-medium micromolar range. Interaction of these compounds with the Ape1 protein was observed by mass spectrometry. These molecules also potentiate the cytotoxicity of the chemotherapeutic agent methyl methanesulfonate in fibrosarcoma cells. This study demonstrates the power of docking and virtual screening techniques as initial steps in the design of new drugs, and opens the door to the development of a new generation of Ape1 inhibitors., Fondo de Investigaciones Sanitarias (grant PI06/1250); Ministerio Ciencia e Innovación (grant CTQ-2010-20541-C03-03); Comunidad de Madrid (SBIO-0214-2006 BIPEDD and S2010 BMD-2457 BIPEDD2); Generalitat de Catalunya; Instituto de Salud Carlos III; AMAROUTO

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the central nervous system, and diseases that associate a deficiency in GABA might benefit from GABAergic drugs. Cerebellar Purkinje cells employ GABA as a neurotransmitter. Cortical cerebellar atrophy (CCA) shows Purkinje cell loss, and ataxia caused by it was alleviated by gabapentin and pregabalin. Thus, CCA is proposed as a model of selective deficiency in GABA in the cerebellum, which benefits clinically from administration of GABAergic drugs, in a manner similar in which levodopa improves motor manifestations in Parkinson’s disease. Other ataxias also benefited clinically from GABAergic drugs, as adult-onset GM2 gangliosidosis, olivopontocerebellar atrophy, cerebellar ataxia with hypogonadism, spinocerebellar ataxias 1, 2 and 6, and adult-onset ataxia-telangiectasia. Complex neurochemical diseases, as multiple-system atrophy, had ataxia worsened by GABAergic drugs. Various disorders with a deficiency in GABA content had their manifestations relieved by admistration of GABAergic drugs, as one patient with progressive encephalomyelitis with rigidity, whose muscular spasms were suppressed by a combination of gabapentin and tiagabine, and another with diaphragmatic myoclonus, who required gabapentin and tiagabine for symptomatic control. On the contrary, GABAergic drugs were not effective in cervical dystonia, amyotrophic lateral sclerosis, Parkinson’s disease and progressive supranuclear palsy, presumably because a deficiency in GABA is not an essential neurochemical abnormality in these diseases. Research aimed at identifying effective therapies to treat cerebellar ataxias and other motor disorders of the central nervous system is warranted. Meanwhile, therapeutic tests with GABAergic drugs might yield clinical improvement in these diseases.

Au- and iron-based magnetic nanoparticles (NPs) are promising NPs for biomedical applications due to their unique properties. The combination of a gold coating over a magnetic core puts together the benefits from adding the magnetic properties to the robust chemistry provided by the thiol functionalization of gold. Here, the use of Au-coated magnetic NPs for molecular detection of a single methylation in DNA aptamer is described. Binding of α-thrombin to two aptamers conjugated to these NPs causes aggregation, a phenomenon that can be observed by UV, DLS and MRI. These techniques discriminate a single methylation in one of the aptamers, preventing aggregation due to the inability of α-thrombin to recognize it. A parallel study with gold and ferromagnetic NPs is detailed, concluding that the Au coating of FexOy NP does not affect their performance and that they are suitable as complex biosensors. These results prove the high detection potency of Au-coated SPIONs for biomedical applications especially for DNA repair detection., The Communities MULTIFUN (contract NMP4-LA-2011-262943) and by “Ministerio Ciencia e Innovación” (grants CTQ-2010-20541-C03-03 and CTQ2014-52588-R) are acknowledged for financial support. Maria Tintoré was supported by a pre-doctoral fellowship (FPI) and a short stay grant (EEBB) from MINECO. Carme Fàbrega is grateful to Fundació La Marató de TV3 (20132032) for a research contract. We thank Dr. Susana Vilchez from the Surface Chemistry group at IQAC-CSIC for her help with the DLS experiments. Laura Polito thanks RSPPTECH—Convenzione Operativa inserita nella Raccolta Convenzioni e Contratti della Regione Lombardia (grant number 18095/RU) and the Italian Ministero dell’Università e della Ricerca (MIUR) (PRIN 2010–2011, contract number 2010JMAZML_003). We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI)

Review: [recent progresses in the use of DNA nanoconstructs for molecular and cellular biology; 150 refs.

The folding of DNA molecules by DNA origami is used in a nanosensor to analyze enzymatic DNA repair activity of hAGT. The method uses conformational changes that condition α-thrombin interaction with DNA aptamers, and illustrates the use of DNA origami as a proteinrecognition biosensor.

The predominant (though not exclusive) reference to degenerative ataxias is due to the fact that the specificity of the affected cell populations should allow anticipation of more or less specific neurochemical alterations. This information could be used to look for therapeutic strategies, given the absence of curative treatments for the majority of ataxic disorders. This review covers only the pharmacologic attempts performed to treat ataxic symptoms, and is not exhaustive in terms of nosology, genetics or congenital errors of metabolism. The neurochemical basis of some non-degenerative ataxias that demonstrate favourable responses to pharmacological treatment are also reviewed. An outline of the physiological neurotransmission in the cerebellum opens this chapter (Table 1).

The thrombin binding aptamer (TBA) is a well characterized chair-like, antiparallel quadruplex structure that binds specifically to thrombin at nanomolar concentrations and therefore it has interesting anticoagulant properties. In this article we review the research involved in the development of new TBA derivatives with improved anticoagulant properties as well as the use of the TBA as a model compound for the study of quadruplex structures. Specifically, we describe the impact of modified nucleosides and non-natural backbones in the guanine tetrads or in the loops and the introduction of pendant groups at the 3' or 5'-ends. The modified oligonucleotides are shown to be excellent tools for the understanding of the molecular structure of the TBA and its folding properties. Finally, we review the use of the TBA-Thrombin recognition system for the development of analytical tools based on the TBA folding., This study was supported by the European Communities (FUNMOL, FP7-NMP- 213382-2), Spanish Ministry of Education (MOL2MED, CTQ2010-20541), the Generalitat de Catalunya (2009/SGR/208), IRB Barcelona, COST (G4net, MP0802) and CIBER-BBN (VI National R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions, Instituto de Salud Carlos III with assistance from the European Regional Development Fund.