Investigating the Role of Guanosine on Human Neuroblastoma Cell Differentiation and the Underlying Molecular Mechanisms

Neuroblastoma arises from neural crest cell precursors failing to complete the process of differentiation. Thus, agents helping tumor cells to differentiate into normal cells can represent a valid therapeutic strategy. Here, we evaluated whether guanosine (GUO), a natural purine nucleoside, which is able to induce differentiation of many cell types, may cause the differentiation of human neuroblastoma SH-SY5Y cells and the molecular mechanisms involved. We found that GUO, added to the cell culture medium, promoted neuron-like cell differentiation in a time- and concentration-dependent manner. This effect was mainly due to an extracellular GUO action since nucleoside transporter inhibitors reduced but not abolished it. Importantly, GUO-mediated neuron-like cell differentiation was independent of adenosine receptor activation as it was not altered by the blockade of these receptors. Noteworthy, the neuritogenic activity of GUO was not affected by blocking the phosphoinositide 3-kinase pathway, while it was reduced by inhibitors of protein kinase C or soluble guanylate cyclase. Furthermore, the inhibitor of the enzyme heme oxygenase-1 but not that of nitric oxide synthase reduced GUO-induced neurite outgrowth. Interestingly, we found that GUO was largely metabolized into guanine by the purine nucleoside phosphorylase (PNP) enzyme released from cells. Taken together, our results suggest that GUO, promoting neuroblastoma cell differentiation, may represent a potential therapeutic agent; however, due to its spontaneous extracellular metabolism, the role played by the GUO-PNP-guanine system needs to be further investigated

Guanine inhibits the growth of human glioma and melanoma cell lines by interacting with GPR23

Guanine-based purines (GBPs) exert numerous biological effects at the central nervous system through putative membrane receptors, the existence of which is still elusive. To shed light on this question, we screened orphan and poorly characterized G protein-coupled receptors (GPRs), selecting those that showed a high purinoreceptor similarity and were expressed in glioma cells, where GBPs exerted a powerful antiproliferative effect. Of the GPRs chosen, only the silencing of GPR23, also known as lysophosphatidic acid (LPA) 4 receptor, counteracted GBP-induced growth inhibition in U87 cells. Guanine (GUA) was the most potent compound behind the GPR23-mediated effect, acting as the endpoint effector of GBP antiproliferative effects. Accordingly, cells stably expressing GPR23 showed increased sensitivity to GUA. Furthermore, while GPR23 expression was low in a hypoxanthine-guanine phosphoribosyl-transferase (HGPRT)-mutated melanoma cell line showing poor sensitivity to GBPs, and in HGPRT-silenced glioma cells, GPR23-induced expression in both cell types rescued GUA-mediated cell growth inhibition. Finally, binding experiments using [H-3]-GUA and U87 cell membranes revealed the existence of a selective GUA binding (K-D = 29.44 & PLUSMN; 4.07 nM; Bmax 1.007 & PLUSMN; 0.035 pmol/mg prot) likely to GPR23. Overall, these data suggest GPR23 involvement in modulating responses to GUA in tumor cell lines, although further research needs to verify whether this receptor mediates other GUA effects

Natural vitamin B12 and fucose supplementation of green smoothies with edible algae and related quality changes during their shelf life

Background. Some algae are an excellent sources of vitamin B12, of special interest for vegetarian/vegan consumers, and of fucose to supplement fruit and vegetable beverages such as smoothies. Nevertheless, supplementation of smoothies with algae may lead to possible quality changes during smoothie shelf life that need to be studied. Therefore, the quality changes in fresh green smoothies supplemented (2.2%) with nine edible algae (sea lettuce, kombu, wakame, thongweed, dulse, Irish moss, nori, Spirulina and Chlorella) were studied throughout 24 days at 5 °C. Results. The initial vitamin C content – 238.7–326.0 mg kg−1 fresh weight (FW) – of a 200 g portion of any of the smoothies ensured full coverage of its recommended daily intake, and still supplying 50–60% of the recommended intake after 7 days. Chlorella and Spirulina smoothies showed the highest vitamin B12 content (33.3 and 15.3 µg kg−1 FW, respectively), while brown algae showed fucose content of 141.1–571.3 mg kg−1 FW. These vitamin B12 and fucose contents were highly maintained during shelf life. Conclusion. The Spirulina supplementation of a 200 g smoothie portion ensured full coverage of the recommended vitamin B12 intake, with lower vitamin C degradation, during a shelf life of 17 days. Furthermore, thongweed and kombu are also considered as excellent fucose sources with similar shelf life.The authors are grateful to Spanish Ministry of Economy and Competitiveness, Project AGL2013−48830−C2−1−R and FEDER for financial support. We would also like to thank SAKATA SEED IBERICA S.L. for providing Bimi® samples

Evaluación de cultivares de trigo candeal Campaña agrícola 2016/17

La pasada campaña se caracterizó por un marcado estrés hídrico-térmico desde octubre a cosecha. Se obtuvieron bajos rendimientos, pesos hectolítricos y pesos de mil granos. El contenido de proteína superó el 17%. No ocurrieron condiciones predisponentes para el desarrollo de enfermedadesEEA BarrowFil: Larsen, Adelina Olga. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Barrow; ArgentinaFil: Di Pane, Francisco. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Barrow; ArgentinaFil: Molfese, Elena Rosa. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Integrada Barrow; ArgentinaFil: Astiz, Valentina. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Integrada Barrow; ArgentinaFil: Wehrhahne, Nilda Liliana. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Barrow; Argentin

The Guanine-Based Purinergic System: The Tale of An Orphan Neuromodulation

Guanine-based purines (GBPs) have been recently proposed to be not only metabolic agents but also extracellular signaling molecules that regulate important functions in the central nervous system. In such way, GBPs-mediated neuroprotection, behavioral responses and neuronal plasticity have been broadly described in the literature. However, while a number of these functions (i.e., GBPs neurothophic effects) have been well-established, the molecular mechanisms behind these GBPs-dependent effects are still unknown. Furthermore, no plasma membrane receptors for GBPs have been described so far, thus GBPs are still considered orphan neuromodulators. Interestingly, an intricate and controversial functional interplay between GBPs effects and adenosine receptors activity has been recently described, thus triggering the hypothesis that GBPs mechanism of action might somehow involve adenosine receptors. Here, we review recent data describing the GBPs role in the brain. We focus on the involvement of GBPs regulating neuronal plasticity, and on the new hypothesis based on putative GBPs receptors. Overall, we expect to shed some light on the GBPs world since although these molecules might represent excellent candidates for certain neurological diseases management, the lack of putative GBPs receptors precludes any high throughput screening intent for the search of effective GBPs-based drugs

The guanine-based purinergic system: the tale of an orphan neuromodulation

Guanine-based purines (GBPs) have been recently proposed to be not only metabolic agents but also extracellular signaling molecules that regulate important functions in the central nervous system. In such way, GBPs-mediated neuroprotection, behavioral responses and neuronal plasticity have been broadly described in the literature. However, while a number of these functions (i.e., GBPs neurothophic effects) have been well-established, the molecular mechanisms behind these GBPs-dependent effects are still unknown. Furthermore, no plasma membrane receptors for GBPs have been described so far, thus GBPs are still considered orphan neuromodulators. Interestingly, an intricate and controversial functional interplay between GBPs effects and adenosine receptors activity has been recently described, thus triggering the hypothesis that GBPs mechanism of action might somehow involve adenosine receptors. Here, we review recent data describing the GBPs role in the brain. We focus on the involvement of GBPs regulating neuronal plasticity, and on the new hypothesis based on putative GBPs receptors. Overall, we expect to shed some light on the GBPs world since although these molecules might represent excellent candidates for certain neurological diseases management, the lack of putative GBPs receptors precludes any high throughput screening intent for the search of effective GBPs-based drugs

An efficient and high-throughput approach for experimental validation of novel human gene predictions

AbstractA highly automated RT-PCR-based approach has been established to validate novel human gene predictions with no prior experimental evidence of mRNA splicing (ab initio predictions). Ab initio gene predictions were selected for high-throughput validation using predicted protein classification, sequence similarity to other genomes, colocalization with an MPSS tag, or microarray expression. Initial microarray prioritization followed by RT-PCR validation was the most efficient combination, resulting in approximately 35% of the ab initio predictions being validated by RT-PCR. Of the 7252 novel genes that were prioritized and processed, 796 constituted real transcripts. In addition, high-throughput RACE successfully extended the 5′ and/or 3′ ends of >60% of RT-PCR-validated genes. Reevaluation of these transcripts produced 574 novel transcripts using RefSeq as a reference. RT-PCR sequencing in combination with RACE on ab initio gene predictions could be used to define the transcriptome across all species

Correction. "The 5th edition of The World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms" Leukemia. 2022 Jul;36(7):1720-1748

We herein present an overview of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms

Evolving trends in the management of acute appendicitis during COVID-19 waves. The ACIE appy II study

Background: In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak. Methods: From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study. Results: A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM. Conclusion: Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide

Downstream Services for Rice Crop Monitoring in Europe: From Regional to Local Scale

The ERMES agromonitoring system for rice cultivations integrates EO data at different resolutions, crop models, and user-provided in situ data in a unified system, which drives two operational downstream services for rice monitoring. The first is aimed at providing information concerning the behavior of the current season at regional/rice district scale, while the second is dedicated to provide farmers with field-scale data useful to support more efficient and environmentally friendly crop practices. In this contribution, we describe the main characteristics of the system, in terms of overall architecture, technological solutions adopted, characteristics of the developed products, and functionalities provided to end users. Peculiarities of the system reside in its ability to cope with the needs of different stakeholders within a common platform, and in a tight integration between EO data processing and information retrieval, crop modeling, in situ data collection, and information dissemination. The ERMES system has been operationally tested in three European rice-producing countries (Italy, Spain, and Greece) during growing seasons 2015 and 2016, providing a great amount of near-real-time information concerning rice crops. Highlights of significant results are provided, with particular focus on real-world applications of ERMES products and services. Although developed with focus on European rice cultivations, solutions implemented in the ERMES system can be, and are already being, adapted to other crops and/or areas of the world, thus making it a valuable testing bed for the development of advanced, integrated agricultural monitoring systems