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Purine nucleotides and nucleosides play critical roles in various pathological conditions, including tumor cell growth. Adenosine triphosphate (ATP) activates pro-tumor receptors, while adenosine (ADO) is a potent immunosuppressant and modulator of cell growth. This study aims to analyze the purinergic actions of ATP and its metabolites, associated enzymes, and P1 or P2 class receptors in primary central nervous system tumors. Additionally, we sought to correlate the levels of nucleosides and the density of P1, P2X, and P2Y receptors in cells with tumor progression. The results indicate that purinergic signaling depends on the receptor concentration and signaling molecules specific to each cell type, tissue, and tumor histology. The purinergic system may function as either a tumor-promoting agent or an antitumor factor, depending on the microenvironmental conditions and the concentrations of receptors and their respective activators. Notably, ATP emerges as the most significant extracellular signal, capable of being converted into other cellular stimulators pertinent to neoplasms, such as adenosine diphosphate, adenosine monophosphate, adenosine, and inosine. Consequently, a cascade of responses to these stimuli promotes tumor development, cell division, and metastasis. Purine nucleotides in central nervous system tumors are pivotal in cellular responses in glioblastoma multiforme, vestibular schwannoma, medulloblastoma, adenomas, gliomas, meningiomas, and pineal tumors. These findings hold the potential for developing novel therapeutic strategies and aiding in therapeutic management.

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Chronic kidney disease (CKD) is a condition characterized by abnormalities in kidney structure and function that persist for more than 3 months. It is estimated that more than 800 million people in the world have a diagnosis of CKD. To remove the harmful metabolic substances from the body, people with CKD need to perform hemodialysis. Due to their beneficial effects against a wide range of clinical conditions, physical exercise is considered a non-pharmacological therapy. This study aimed to evaluate the beneficial effects of resistance exercise during hemodialysis on metabolic adipokines, myokines, body weight, and glomerular filtration rate in patients living with CKD. Briefly, the blood samples were collected in two moments: immediately before the start of the resistance exercise protocol and 1 week after the end of the protocol. Resistance exercise protocol was performed thrice a week for 12 weeks and applied during hemodialysis sessions. Here, resistance exercise increases the circulating irisin (14.56%; p = 0.0112), handgrip strength (5.70%; p = 0.0036), glomerular filtration rate (25.9%; p = 0.022) and significantly decreases adiponectin (- 55.7%; p = 0.0044), body weight (- 3.7%; p = 0.0001), glucose (- 22%; p = 0.009), and albumin levels (- 9.55%; p = 0.0001). Conversely, leptin levels (- 10.9%; p = 0.38), iron (3.05%; p = 0.705), ferritin (3.24%; p = 0.880), hemoglobin (- 0.52%; p = 0.75), total cholesterol (7.9%; p = 0.19), LDL (- 9.99%; p = 0.15) and HDL (- 4.8%; p = 0.45), did not change after resistance exercise. Interestingly, 1,25 hydroxyvitamin D levels were significantly increased (14.5%; p = 0.01) following resistance exercise. Considering the effect of sex (males vs. females), we found that irisin levels increased in females but not in males after the resistance exercise protocol. Furthermore, handgrip strength and body weight were different, indicating that males had the highest strength and weight. We demonstrated that both males and females had lower albumin levels after the resistance exercise protocol. In conclusion, we suggest that resistance exercise has beneficial effects in the CKD population by modulating adipokines and metabolic myokines and therefore can be used as a non-pharmacological adjunctive therapy in CKD patients undergoing HD.

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The word sarcopenia derives from the Greek terms "sarx" for meat and "penia" for loss, thus being used to define reductions in muscle mass, muscle strength, and lower physical performance that compromise, mainly, the elderly population. Its high negative impact on patients' quality of life encourages the production and publication of new studies that seek to find methods to prevent and reverse cases of loss of muscle mass and strength. Furthermore, the high prevalence of sarcopenia in patients with chronic kidney disease (CKD) is closely related to its pathophysiology, which consists of a state of increased protein catabolism and decreased muscle tissue synthesis. Also considering the inflammatory nature of CKD and sarcopenia, the purinergic system has been an important target of studies, which seek to relate it to the two previous conditions. This system achieves anti-inflammatory action by inhibiting, through adenosine, pro-inflammatory factors such as interleukin-12 (IL-12), tumor necrosis factor alpha (TNF-α), and nitric oxide (NO), as well as by releasing anti-inflammatory substances such as interleukin-10 (IL-10). Simultaneously, the purinergic system presents pro-inflammatory activity, signaled by adenosine triphosphate (ATP), which occurs through the activation of T cells and the release of pro-inflammatory factors such as those mentioned above. Therefore, the ability of this system to act on inflammatory processes can promote positive and negative changes in the clinical aspect of patients with CKD and/or sarcopenia. Furthermore, it appears that there is a correlation between the practice of repeated physical exercise with the clinical improvement and in the quality of life of these patients, presenting a decrease in the levels of C-reactive protein (CRP), NTPDase, and the pro-inflammatory cytokine IL-6, such as increases in IL-10 resulting from modulation of the purinergic system. In this way, the present article seeks to evaluate the effect of physical exercise as a modulator of the purinergic system in the control of sarcopenia in patients with CKD on hemodialysis, in order to trace a relationship that can bring benefits both for biological markers and for quality of life of these patients.

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Cystic fibrosis is a monogenic and autosomal recessive disease. It is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator gene responsible for encoding the CFTR protein. Involvement of the gastrointestinal and respiratory systems is the main clinical manifestation. In this case, we report a heterozygous CFTR patient harboring class I (p.Gly542*) and class V (c.2657+5G>A) mutations. The importance of this case report lies in the clinical features because the patient, aged 3 years, presented with early exocrine pancreatic insufficiency, which can be considered atypical, as most individuals with this genotype are pancreatic sufficient or develop pancreatic insufficiency later in life. This report aims at presenting the tests requested that contributed to the patient's diagnosis, as well as at understanding the association between these mutations and their phenotypic presentation. Interpretation of the genotype-phenotype relationship represents a challenge, as genetic analysis alone is not sufficient to clearly predict severity of the disease. This is because the significant phenotypic heterogeneity existing among patients with the same genotype may exert socioeconomic and sociocultural influences, or by the action of CFTR modifiers, such as environmental and modifying genes, which can alter the protein's function and exert an impact on the individual's phenotype.

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Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, responsible for the synthesis of the CFTR protein, a chloride channel. The gene has approximately 2000 known mutations and all of them affect in some degree the protein function, which makes the pathophysiological manifestations to be multisystemic, mainly affecting the respiratory, gastrointestinal, endocrine, and reproductive tracts. Currently, the treatment of the disease is restricted to controlling symptoms and, more recently, a group of drugs that act directly on the defective protein, known as CFTR modulators, was developed. However, their high cost and difficult access mean that their use is still very restricted. It is important to search for safe and low-cost alternative therapies for CF and, in this context, natural compounds and, mainly, caffeic acid phenethyl ester (CAPE) appear as promising strategies to assist in the treatment of the disease. CAPE is a compound derived from propolis extracts that has antioxidant and anti-inflammatory activities, covering important aspects of the pathophysiology of CF, which points to the possible benefit of its use in the disease treatment. To date, no studies have effectively tested CAPE for CF and, therefore, we intend with this review to elucidate the role of inflammation and oxidative stress for tissue damage seen in CF, associating them with CAPE actions and its pharmacologically active derivatives. In this way, we offer a theoretical basis for conducting preclinical and clinical studies relating the use of this molecule to CF.

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The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is widely used in agriculture to control various weeds. The objective of this study was to use the digital image processing method to identify alveolar lesions in the lungs of rats submitted to chronic 2,4-dichlorophenoxyacetic acid (2,4-D) inhalation exposure. We used forty adult male Wistar rats. The rats were divided into four groups: control group (CG), low concentration group (LCG), medium concentration group (MCG), and high concentration group (HCG). In a 6-month exposure period, we used two boxes connected to ultrasonic nebulizers for herbicide spraying. After this period, the rats were euthanized for the collection and study of lung tissue. For each image, counts of injuries and blisters were performed automatically using a methodology based on digital image processing techniques. For analysis of the results, an electronic database (Excel®) was created. We used the Pearson method for correlation analysis; values of p <0.05 were considered significant. In the evaluation of healthy alveoli, we recorded positive and significant correlations between analysis from a pathologist and computational analysis. In the evaluation of injured alveoli, we recorded a positive but non-significant correlation between analysis from a pathologist and computational analysis. These results show the effectiveness of digital image processing when evaluating alveolar integrity.

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OBJECTIVE AND DESIGN: The exacerbate inflammatory response contributes to the progressive loss of lung function in cystic fibrosis (CF), a genetic disease that affects the osmotic balance of mucus and mucociliary clearance, resulting in a microenvironment that favors infection and inflammation. The purinergic system, an extracellular signaling pathway characterized by nucleotides, enzymes and receptors, may have a protective role in the disease, through its action in airway surface liquid (ASL) and anti-inflammatory response. MATERIALS AND METHODS: To make up this review, studies covering topics of CF, inflammation, ASL and purinergic system were selected from the main medical databases, such as Pubmed and ScienceDirect. CONCLUSION: We propose several ways to modulate the purinergic system as a potential therapy for CF, like inhibition of P2X7, activation of P2Y2, A2A and A2B receptors and blocking of adenosine deaminase. Among them, we postulate that the most suitable strategy is to block the action of adenosine deaminase, which culminates in the increase of Ado levels that presents anti-inflammatory actions and improves mucociliary clearance. Furthermore, it is possible to maintain the physiological levels of ATP to control the hydration of ASL. These therapies could correct the main mechanisms that contribute to the progression of CF.

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Breast cancer (BC) is the most frequent cause of death among women, representing a global public health problem. Here, we aimed to discuss the correlation between the purinergic system and BC, recognizing therapeutic targets. For this, we analyzed the interaction of extracellular nucleotides and nucleosides with the purinergic receptors P1 and P2, as well as the influence of ectonucleotidase enzymes (CD39 and CD73) on tumor progression. A comprehensive bibliographic search was carried out. The relevant articles for this review were found in the PubMed, Scielo, Lilacs, and ScienceDirect databases. It was observed that among the P1 receptors, the A1, A2A, and A2B receptors are involved in the proliferation and invasion of BC, while the A3 receptor is related to the inhibition of tumor growth. Among the P2 receptors, the P2X7 has a dual function. When activated for a short time, it promotes metastasis, but when activated for long periods, it is related to BC cell death. P2Y2 and P2Y6 receptors are related to BC proliferation and invasiveness. Also, the high expression of CD39 and CD73 in BC is strongly related to a worse prognosis. The receptors and ectonucleotidases involved with BC become possible therapeutic targets. Several purinergic pathways have been found to be involved in BC cell survival and progression. In this review, in addition to analyzing the pathways involved, we reviewed the therapeutic interventions already studied for BC related to the purinergic system, as well as to other possible therapeutic targets.

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Acute viral respiratory infections are the main infectious disease in the world. In 2020, a new disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronavirus disease 2019 (COVID-19), became a global pandemic. The immune response to the virus depends on factors such as genetics, age and physical state, and its main input receptor is the angiotensin-converting enzyme 2. The practice of physical exercises acts as a modulator of the immune system. During and after physical exercise, pro- and anti-inflammatory cytokines are released, lymphocyte circulation increases, as well as cell recruitment. Such practice has an effect on the lower incidence, intensity of symptoms and mortality in viral infections observed in people who practice physical activity regularly, and its correct execution must be considered to avoid damage. The initial response is given mainly by type I interferons (IFN-I), which drive the action macrophages and lymphocytes, followed by lymphocyte action. A suppression of the IFN-I response has been noted in COVID-19. Severe conditions have been associated with storms of pro-inflammatory cytokines and lymphopenia, as well as circulatory changes and virus dispersion to other organs. The practice of physical activities strengthens the immune system, suggesting a benefit in the response to viral communicable diseases. Thus, regular practice of adequate intensity is suggested as an auxiliary tool in strengthening and preparing the immune system for COVID-19. Further studies are needed to associate physical exercise with SARS-CoV-2 infection.

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Objetivo: identificar os fatores associados às internações por sífilis congênita em neonatos, a partir das características da assistência pré-natal. Materiais e método: estudo quantitativo tipo caso controle, realizado por meio da aplicação de questionário a 65 puérperas com seus bebês internados de julho a novembro de 2017. Os dados foram analisados mediante regressão logística, segundo o plano proposto na abordagem hierárquica. Resultados: 20 % das internações foram por sífilis (casos) e 80 % por outras causas (controle). As variáveis risco de vulnerabilidade (p = 0,036), história prévia de infecção sexualmente transmissível (p = 0,006), uso do contraceptivo oral (p = 0,011) e paridade (p = 0,043) foram estatisticamente significativas. Também foram associadas à ocorrência do desfecho a ausência do parceiro durante a consulta (p = 0,028), a não realização de teste rápido para a sífilis (p = 0,035) e a atividade educativa para o parceiro (p = 0,033), além das variáveis do neonato: baixo peso ao nascer (p = 0,025), não estar em aleitamento materno exclusivo (p = 0,036) e não ter tido contato pele a pele (p = 0,043). Conclusões: a sífilis congênita apresenta diversos fatores de risco para a sua ocorrência. Foi possível observar que as iniquidades assistenciais existentes no atendimento durante as consultas de pré-natal refletem diretamente na ocorrência desse agravo.

Objective: To identify the factors associated with hospitalizations due to congenital syphilis in neonates, based on the characteristics of prenatal care. Materials and method: A quantitative case-control study, conducted by applying a questionnaire to 65 puerperal women with their babies hospitalized from July to November 2017. The data were analyzed using logistic regression, according to the plan proposed in the hierarchical approach. Results: 20% of the hospitalizations were due to syphilis (cases) and 80% to other causes (control). The vulnerability risk (p = 0.036), previous history of sexually transmitted infection (p = 0,006), use of oral contraceptives (p = 0.011) and parity (p = 0.043) variables were statistically significant. The absence of the partner during the consultation (p = 0.028), failure to perform a rapid test for syphilis (p = 0.035) and educational activity for the partner (p = 0.033) were also associated with the occurrence of the outcome, in addition to the variables of the newborn: low birth weight (p = 0.025), not being on exclusive breastfeeding (p = 0.036) and not having had skin-to-skin contact (p = 0.043). Conclusions: Congenital syphilis has several risk factors for its occurrence. It was possible to observe that the assistance inequalities existing in care during the prenatal consultations directly reflect on the occurrence of this condition.

Objetivo: identificar los factores asociados a las hospitalizaciones por sífilis congénita en recién nacidos desde las características de la asistencia prenatal. Materiales y método: estudio cuantitativo tipo caso control, realizado por medio de la aplicación de encuesta a 65 puérperas con sus bebés hospitalizados de julio a noviembre del 2017. Se analizaron los datos mediante regresión logística, de acuerdo con el plan propuesto en el enfoque jerárquico. Resultados: el 20 % de las hospitalizaciones se dio por sífilis (casos) y el 80 % por otras causas (control). Las variables riesgo de vulnerabilidad (p = 0,036), historia previa de infección sexualmente transmisible (p = 0,006), uso del contraceptivo oral (p = 0,011) y paridad (p = 0,043) fueron estadísticamente significativas. Adicionalmente, se asociaron a la ocurrencia del desfecho la ausencia del compañero en la cita (p = 0,028), la no realización de la prueba rápida para detección de sífilis (p = 0,035) y la actividad educativa para el compañero (p = 0,033), además de las variables del neonato: bajo peso al nacer (p = 0,025), no encontrarse en lactancia exclusiva (p = 0,036) y no haber tenido contacto piel con piel (p = 0,043). Conclusiones: la sífilis congénita presenta diversos factores de riesgo para su ocurrencia. Fue posible observar que las iniquidades asistenciales en la atención durante las citas de prenatal refleten directamente en la ocurrencia de este agravo.

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