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The purine nucleobases adenine and guanine are complex organic molecules that are essential for life. Despite their ubiquitous presence on Earth, purines have yet to be detected in observations of astronomical environments. This work therefore proposes to study the infrared spectra of purines linked to terrestrial biochemical processes under conditions analogous to those found in the interstellar medium. The infrared spectra of adenine and guanine, both in neat form and embedded within an ice made of H2O:NH3:CH4:CO:CH3OH (10:1:1:1:1), were analysed with the aim of determining which bands attributable to adenine and/or guanine can be observed in the infrared spectrum of an astrophysical ice analogue rich in other volatile species known to be abundant in dense molecular clouds. The spectrum of adenine and guanine mixed together was also analysed. This study has identified three purine nucleobase infrared absorption bands that do not overlap with bands attributable to the volatiles that are ubiquitous in the dense interstellar medium. Therefore, these three bands, which are located at 1255, 940, and 878 cm-1, are proposed as an infrared spectral signature for adenine, guanine, or a mixture of these molecules in astrophysical ices. All three bands have integrated molar absorptivity values (ψ) greater than 4 km mol-1, meaning that they should be readily observable in astronomical targets. Therefore, if these three bands were to be observed together in the same target, then it is possible to propose the presence of a purine molecule (i.e., adenine or guanine) there.

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Guanosine is a purinergic nucleoside that has been shown to have neuroprotective effects, mainly through its ability to modulate the glutamatergic system. An increase in pro-inflammatory cytokine levels triggers the activation of the enzyme indoleamine 2,3-dioxygenase 1 (IDO-1), leading to glutamatergic excitotoxicity, which has important roles in the pathophysiology of depression. The aim of this study was to investigate the possible antidepressant-like effects and underlying mechanisms of action of guanosine against lipopolysaccharide (LPS)-induced depression in a mouse model. Mice were orally pre-treated with saline (0.9% NaCl), guanosine (8 or 16 mg/kg), or fluoxetine (30 mg/kg) for 7 days before LPS (0.5 mg/kg, intraperitoneal) injection. One day after LPS injection, mice were subjected to the forced swim test (FST), tail suspension test (TST), and open field test (OFT). After the behavioral tests, mice were euthanized and the levels of tumor necrosis factor-α (TNF-α), IDO-1, glutathione, and malondialdehyde in the hippocampus were measured. Pretreatment with guanosine was able to prevent LPS- induced depressive-like behaviors in the TST and FST. In the OFT, no locomotor changes were observed with any treatment. Both guanosine (8 and 16 mg/kg/day) and fluoxetine treatment prevented the LPS-induced increase in TNF-α and IDO expression and lipid peroxidation as well as decrease of reduced glutathione levels in the hippocampus. Taken together, our findings suggest that guanosine may have neuroprotective effects against LPS-induced depressive-like behavior through preventing oxidative stress and the expression of IDO-1 and TNF-α in the hippocampus.

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Background: Pregnancy is characterized as a physiological period with greater sensitivity to insulin resistance and changes in oxidative stress. Purinergic signaling is directly related to diabetes, as this condition modifies the concentration of extracellular ATP and the level of degradation of ATP to adenosine. Objective: Analyze oxidative stress and the purinergic system in pregnant women with Gestational Diabetes Mellitus (GDM) and compare them with low-risk pregnant women (LR). Materials and Methods: The research was of a quantitative approach of an experimental nature. The study was carried out at the Clínica da Mulher, which serves high-risk pregnant women, and at the Family Health Centers, which serves low-risk pregnant women, both located in Chapecó, Santa Catarina, Brazil. Results: From the analysis, it was observed that oxidative stress was increased in pregnant women in LR compared to pregnant women with GDM by increasing the concentration of TBARS and reducing the concentration of Carbonyl Protein in pregnant women with LR. Regarding the purinergic system, there was a significant decrease in the hydrolysis of the nucleotides ATP, ADP, and AMP in pregnant women with GDM, and a significant increase in the hydrolysis of ADA, also in pregnant women with GDM. Conclusion: Therefore, pregnant women with GDM have less oxidative stress compared to pregnant women in LR concerning TBARS and Carbonyl Protein markers, thus allowing a greater antioxidant defense mechanism. Furthermore, concerning the purinergic system, there is an increase in the activity of ADA, which is directly related to the immunosuppression process, a necessary condition for the protection of the fetus during the gestational period (AU).

Introdução: A gravidez é caracterizada como um período fisiológico em que há uma maior sensibilidade a resistência à insulina e alterações no estresse oxidativo. A sinalização purinérgica está diretamente relacionada ao diabetes, pois esta condição modifica a concentração de ATP extracelular e o nível de degradação de ATP em adenosina. Objetivo:Analisar o estresse oxidativo e o sistema purinérgico em gestantes com Diabetes Mellitus Gestacional (DMG) e compará-los com gestantes de baixo risco (BR). Materiais e Métodos: A pesquisa foi de abordagem quantitativa, de caráter experimental. O estudo foi realizado na Clínica da Mulher, que atende gestantes de alto risco, e nas Unidades de Saúde da Família, que atendem gestantes de baixo risco, ambas localizadas no município de Chapecó, Santa Catarina, Brasil. Resultados: A partir das análises, observou-se que o estresse oxidativo apresentou-se aumentado em gestantes de BR quando comparado a gestantes com DMG. No que tange ao sistema purinérgico, houve uma diminuição significativa na hidrólise dos nucleotídeos ATP, ADP e AMP em gestantes com DMG, bem como um aumento significativo na hidrólise de ADA, também em gestantes com DMG. Conclusão: Portanto, gestantes com DMG possuem menor estresse oxidativo quando comparado a gestantes de BR, permitindo assim, um maior mecanismo de defesa antioxidante. Para mais, no que se refere ao sistema purinérgico, verifica-se o aumento da concentração de ADA está diretamente relacionada ao processo de imunossupressão, condição necessária à proteção do feto durante o período gestacional (AU).

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The aims of this study were to evaluate the relationship between attached microbial markers and degradability of forage samples incubated in vitro and to compare these microbial markers. In Trial 1, the content of 15N, purines, and phosphorus (P) as well as xylanase activity in residue of different forage species were measured after 24 h of incubation in a conventional in vitro system at pH 6.8. Trial 2 used the same procedures as those of Trial 1 except that forage samples were incubated in media with different initial pH (5.5, 6.0, 6.5, or 7.0). There was no correlation (P > 0.10) between forage degradability and either microbial marker in Trial 1. Degradability of both, bermuda and ryegrass, and the content of all markers in the incubation residues was positively affected by increased pH (P < 0.05). The content of 15N in residues was linearly related to xylanase activity (P < 0.05) but not with P or purines content. In conclusion, the nutritional potential of different forage species may not to be compared, based on the content of microbial markers in the incubation residues. In other way, within a forage species, the in vitro degradation was directly associated to either marker. However, P presents analytical advantage over other markers.

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La hipoxantina y la xantina son biomarcadores metabólicos que resultan de la degradación de las proteínas purinas. Los análisis cienciométricos constituyen una herramienta para estudiar las publicaciones científicas en torno a un determinado tema con la finalidad de determinar tendencias en la literatura. Se realizó un análisis cienciométrico de la producción científica reciente sobre la hipoxantina y xantina en el ejercicio, publicada en la base de datos Scopus durante el período 2016 - 2021. Para la búsqueda en Scopus se utilizaron las palabras clave en idioma inglés: exercise, hypoxanthine y xanthine. Se realizó un análisis cuantitativo, tomando en cuenta los artículos encontrados, así como la información proporcionada por el software VOSviewer. Se identificaron 64 artículos, de estos, 56 fueron de investigación aplicada y ocho de revisión. La categoría de efecto del ejercicio tuvo una mayor cantidad de estudios con 23; dentro de esta se encuentra la subcategoría de metabolismo que presentó 21 artículos. Tanto Estados Unidos como Polonia son los países con mayor número de publicaciones. Existen distintos enfoques y protocolos de ejercicio utilizados para cuantificar la respuesta de la hipoxantina y xantina, así como los perfiles de los sujetos de estudio utilizados como muestra para las investigaciones. La cuantificación de hipoxantina y xantina en el cuerpo es importante para la investigación en el campo de las ciencias del ejercicio(AU)

Hypoxanthine and xanthine are metabolic biomarkers that result from the degradation of purine proteins. Scientometric analyzes constitute a tool to study scientific publications around a certain topic in order to determine trends in the literature. A scientometric analysis was carried out of the recent scientific production on hypoxanthine and xanthine in exercise, published in Scopus database during the period 2016-2021. For the search in Scopus, we used the English keywords exercise, hypoxanthine and xanthine. A quantitative analysis was carried out, taking into account the articles found, as well as the information provided by VOSviewer software. Sixty-four articles were identified, 56 of them were applied research and eight were review. The exercise effect category had a larger number of studies (23). Here there is a subcategory of metabolism that had 21 articles. The United States and Poland are both the countries with the highest number of publications. There are different approaches and exercise protocols used to quantify the response of hypoxanthine and xanthine, as well as the profiles of the study subjects used as a sample for the investigations. The quantification of hypoxanthine and xanthine in the body is important for research in the field of exercise science(AU)

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Guanine (Gua), among purines, is a preferred oxidation/nitration target because of its low one-electron redox potential. The reactive oxygen/nitrogen species peroxynitrite (ONOO-), produced in vivo by the reaction between nitric oxide (•NO) and superoxide radical (O2•‒), is responsible for several oxidative modifications in biomolecules, including nitration, nitrosation, oxidation, and peroxidation. In particular, the nitration of Gua, although detected, as well as its reaction kinetics have been seldom investigated. Thus, we studied the concentration- and temperature-dependent formation of 8-nitroguanine (8-NitroGua) in phosphate buffer (pH 7.40) using stopped-flow spectrophotometry. Traces showed a biexponential behavior, with best-fit rate constants: kfast = 4.4 s-1 and kslow = 0.41 s-1 (30 °C, 400 µM both Gua and ONOO-). kfast increased linearly with the concentration of both reactants whereas kslow was concentration-independent. Linear regression analysis of kfast as a function of Gua and ONOO- concentration yielded values of 2.5-6.3 × 103 M-1s-1 and 1.5-3.5 s-1 for the second-order (slope) and first-order (ordinate) rate constants, respectively (30 °C). Since ONOO- is a short-lived species, its decay kinetics was also taken into account for this analysis. The 8-NitroGua product was stable for at least 4 h, so no spontaneous denitration was observed. Stopped-flow assays using antioxidants and free-radical scavengers suggested a mixed direct/indirect reaction mechanism for 8-NitroGua formation. Gua nitration by ONOO- was also observed in the presence of physiologically relevant CO2 concentrations. The reaction product identity, its yield (∼4.2%, with 400 µM ONOO- and 200 µM Gua), and the reaction mechanism were unequivocally determined by HPLC-MS/MS experiments. In conclusion, 8-NitroGua production at physiologic pH reached significant levels in a few hundred milliseconds, suggesting that the process might be kinetically relevant in vivo and can likely cause permanent nitrative damage to DNA bases.

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Emerging and re-emerging viruses have been a challenge in public health in recent decades. Host-targeted antivirals (HTA) directed at cellular molecules or pathways involved in virus multiplication represent an interesting strategy to combat viruses presently lacking effective chemotherapy. HTA could provide a wide range of agents with inhibitory activity against current and future viruses that share similar host requirements and reduce the possible selection of antiviral-resistant variants. Nucleotide metabolism is one of the more exploited host metabolic pathways as a potential antiviral target for several human viruses. This review focuses on the antiviral properties of the inhibitors of pyrimidine and purine nucleotide biosynthesis, with an emphasis on the rate-limiting enzymes dihydroorotate dehydrogenase (DHODH) and inosine monophosphate dehydrogenase (IMPDH) for which there are old and new drugs active against a broad spectrum of pathogenic viruses.

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We have proposed that the abiogenesis of life around the beginning of the Archean may have been an example of "spontaneous" microscopic dissipative structuring of UV-C pigments under the prevailing surface ultraviolet solar spectrum. The thermodynamic function of these Archean pigments (the "fundamental molecules of life"), as for the visible pigments of today, was to dissipate the incident solar light into heat. We have previously described the non-equilibrium thermodynamics and the photochemical mechanisms which may have been involved in the dissipative structuring of the purines adenine and hypoxanthine from the common precursor molecules of hydrogen cyanide and water under this UV light. In this article, we extend our analysis to include the production of the other two important purines, guanine and xanthine. The photochemical reactions are presumed to occur within a fatty acid vesicle floating on a hot (∼80 ∘C) neutral pH ocean surface exposed to the prevailing UV-C light. Reaction-diffusion equations are resolved under different environmental conditions. Significant amounts of adenine (∼10-5 M) and guanine (∼10-6 M) are obtained within 60 Archean days, starting from realistic concentrations of the precursors hydrogen cyanide and cyanogen (∼10-5 M).

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Purinergic signaling modulates immune function and is involved in the immunopathogenesis of several viral infections. This study aimed to investigate alterations in purinergic pathways in coronavirus disease 2019 (COVID-19) patients. Mild and severe COVID-19 patients had lower extracellular adenosine triphosphate and adenosine levels, and higher cytokines than healthy controls. Mild COVID-19 patients presented lower frequencies of CD4+ CD25+ CD39+ (activated/memory regulatory T cell [mTreg]) and increased frequencies of high-differentiated (CD27- CD28- ) CD8+ T cells compared with healthy controls. Severe COVID-19 patients also showed higher frequencies of CD4+ CD39+ , CD4+ CD25- CD39+ (memory T effector cell), and high-differentiated CD8+ T cells (CD27- CD28- ), and diminished frequencies of CD4+ CD73+ , CD4+ CD25+ CD39+ mTreg cell, CD8+ CD73+ , and low-differentiated CD8+ T cells (CD27+ CD28+ ) in the blood in relation to mild COVID-19 patients and controls. Moreover, severe COVID-19 patients presented higher expression of PD-1 on low-differentiated CD8+ T cells. Both severe and mild COVID-19 patients presented higher frequencies of CD4+ Annexin-V+ and CD8+ Annexin-V+ T cells, indicating increased T-cell apoptosis. Plasma samples collected from severe COVID-19 patients were able to decrease the expression of CD73 on CD4+ and CD8+ T cells of a healthy donor. Interestingly, the in vitro incubation of peripheral blood mononuclear cell from severe COVID-19 patients with adenosine reduced the nuclear factor-κB activation in T cells and monocytes. Together, these data add new knowledge to the COVID-19 immunopathology through purinergic regulation.

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Continuing with our program to obtain new histamine H3 receptor (H3R) ligands, in this work we present the synthesis, H3R affinity and in silico studies of a series of eight new synthetically accessible purine derivatives. These compounds are designed from the isosteric replacement of the scaffold presented in our previous ligand, pyrrolo[2,3-d]pyrimidine ring, by a purine core. This design also considers maintaining the fragment of bipiperidine at C-4 and aromatic rings with electron-withdrawing groups at N-9, as these fragments are part of the proposed pharmacophore. The in vitro screening results show that two purine derivatives, 3d and 3h, elicit high affinities to the H3R (Ki values of 2.91 and 5.51 nM, respectively). Both compounds are more potent than the reference drug pitolisant (Ki 6.09 nM) and show low toxicity with in vitro models (IC50 > 30 µM on HEK-293, SH-SY5Y and HepG2 cell lines). Subsequently, binding modes of these ligands are obtained using a model of H3R by docking and molecular dynamics studies, thus determining the importance of the purine ring in enhancing affinity due to the hydrogen bonding of Tyr374 to the N-7 of this heterocycle. Finally, in silico ADME properties are predicted, which indicate a promising future for these molecules in terms of their physical−chemical properties, absorption, oral bioavailability and penetration in the CNS.