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A number of studies have shown that oxidative stress is related to the pathogenesis of several immunological diseases, such as Hashimoto's thyroiditis (HT), although there is no plausible mechanism to explain it. Thus, we aimed at hypothesizing and providing some possible mechanisms linking oxidative stress to autoimmunity aspects and its implications for HT, as well as adjuvant therapeutic proposals to mitigate the deleterious effects. Our hypothesis is that deficient eating habits, autoimmune regulator gene predisposing gene, dysbiosis and molecular mimicry, unfolded proteins and stress in the endoplasmic reticulum, and thymus involution appear to be the main potential factors leading to HT oxidative stress. Likewise, we show that the use of minerals selenium and zinc, vitamins D and C, as well as probiotics, can be interesting adjuvant therapies for the control of oxidative damage and poor prognosis of HT. Further clinical trials are needed to understand the real beneficial and side effects of these supplements.

Defined by the World Health Organization as a global public health pandemic, coronavirus 2019 (COVID-19) has a global impact and has caused the death of thousands of people. The "severe acute respiratory syndrome coronavirus 2" virus (SARS-CoV-2) is the etiologic agent of this disease, which uses the angiotensinconverting enzyme receptor 2 (ACE2) to infect the body, so any organ that expresses the gene ACE2 is a possible target for the new coronavirus. In addition, in severe cases of COVID-19, a cytokine storm occurs, which triggers widespread systemic inflammation due to the uncontrolled release of proinflammatory cytokines. In this perspective, the modulation of purinergic receptors is highlighted in the literature as a possible therapy, considering its application in other viral infections and systemic inflammation. Therefore, this review aims to gather information on the modulation of the P2X7 receptor in the main organs directly affected by the virus and by the cytokine storm: the heart, brain, lung, liver and kidneys. Thus, demonstrating possible therapies for reducing inflammation and the level of morbidity and mortality of COVID-19. In severe cases of COVID-19, SARS-CoV-2 infection is capable of triggering an exacerbated release of cytokines, called a cytokine storm. With this inflammation, or less the direct infection of the virus, the whole organism can be affected. In this way, major and important organs such as the heart, lung, brain, and liver are affected, triggering different pathologies. In this perspective, purinergic signaling is highlighted in the literature for its anti-inflammatory role and has been listed in the pandemic scenario as a potential therapy. Therefore, knowing the expression of the purinergic receptor P2X7 in these tissues, the modulation of its inflammatory activity may be favorable in this severe and systemic condition.

Neuroinflammation is closely related to the development of depression, since the latter is caused, among other factors, by inflammatory processes, mainly related to the activation of microglia and expression of specific genes, which occurs during the neuroinflammatory process. Thus, COVID-19 is an important risk factor for the development of depression, since in addition to generating the feeling of stress, which also increases the activity of the immune system, it is also the cause of pathological processes and physiological ones that lead to the development of neuroinflammation, microglial activation, gene expression dysfunction and decreased concentration of available serotonin. That said, drugs are being used to combat COVID-19 to reduce the oxidative stress presented in the disease. Thus, tramadol and fluoxetine are highlighted as drugs used, however, although they present some positive results, such as the reduction of pro-inflammatory cytokines, they are also associated with negative effects such as dependence, pulmonary, cardiac and brain impairment. From this, the purinergic system is highlighted in the literature as a possible therapeutic target. This is because its mechanisms are related to the regulation of microglia, astrocytes and the physiology of important neurotransmitters and hormones. Added to this, there is a modulation of inflammatory activity, especially with regard to the P2X7 receptors of this system. The latter is an important target for the treatment of depression and COVID-19, since positive results were obtained through the genetic exclusion of this receptor and the use of selective antagonists.

COVID-19 is associated with oxidative stress, peripheral hyper inflammation, and neuroinflammation, especially in individuals with a more severe form of the disease. Some studies provide evidence on the onset or exacerbation of major depressive disorder (MDD), among other psychiatric disorders due to COVID-19. Oxidative stress and neuroinflammation are associated conditions, especially in the more severe form of MDD and in refractoriness to available therapeutic strategies. Inflammatory cytokines in the COVID-19 hyper inflammation process can activate the hypothalamic-pituitary-adrenal (HPA) axis and the indoleamine-2,3-dioxygenase (IDO) enzyme. IDO activation can reduce tryptophan and increase toxic metabolites of the kynurenine pathway, which increases glial activation, neuroinflammation, toxicity, and neuronal death. This review surveyed a number of studies and analyzed the mechanisms of oxidative stress, inflammation, and neuroinflammation involved in COVID-19 and depression. Finally, the importance of more protocols that can help elucidate the interaction between these mechanisms underlying COVID-19 and MDD and the possible therapeutic strategies involved in the interaction of these mechanisms are highlighted.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has significantly impacted the world and has driven many researchers into the pathophysiology of COVID-19. In the findings, there is a close association between purinergic signaling and the immune response. Then, this study aimed to evaluate alterations in the purinergic signaling in COVID-19 patients according to range severity. We divided the COVID-19 patients into moderate and severe cases following the guideless of NIH and WHO, together with clinical characteristics. The blood samples were collected to obtain PBMCs and platelets. We analyzed the ectonucleotidase activities through ATP, ADP, AMP, Ado hydrolysis, E-NTPDase1 (CD39), and 5'-NT (CD73) expression by flow cytometry in total leukocytes. The extracellular ATP was measured by bioluminescence, and cytokines were analyzed by flow cytometry. We observed a decrease in ATP hydrolysis and increased AMP hydrolysis in PBMCs for both groups. In severe cases, ATP hydrolysis was raised for the platelets, while ADP and AMP hydrolysis have risen significantly in both groups. Additionally, there was a significant increase in ADP hydrolysis in severe cases compared to moderate cases. In addition, we observed an increase in the ADA activity in platelets of moderate patients. Moderate and severe cases showed increased expression of CD39 and CD73 in total leukocytes. To finalize the purinergic signaling, extracellular ATP was increased in both groups. Furthermore, there was an increase in IL-2, IL-6, IL-10, and IL-17 in moderate and severe groups. Thus, for the first time, our findings confirm the changes in purinergic signaling and immune response in COVID-19, in addition to making it more evident that the severity range directly impacts these changes. Therefore, the therapeutic potential of the purinergic system must be highlighted and studied as a possible target for the treatment of SARS-CoV-2 disease. KEY MESSAGES: COVID-19 patients exhibit alterations in purinergic system and immune response. High levels of extracellular ATP lead to different inflammatory responses. CD39 and CD73 expression were increased in COVID-19 patients. Cytokines IL-2, IL-6, IL-10, and IL-17 also were altered in these patients. The purinergic system may be a possibility target to SARS-CoV-2 treatments.

Diabetes mellitus (DM) and arterial hypertension are considered serious public health problems. Several studies have shown that oxidative stress is usually related to the onset of DM and hypertension and their complications. Moreover, levels of some minerals are closely related to the pathophysiology of these diseases. Thus, the present study aimed to evaluate the biochemical markers, minerals and redox profile levels in the serum of patients with type 2 DM and hypertension, as well as to test the effect of metformin on the viability and redox profile of cells. Patients with type 2 DM and hypertension + type 2 DM had higher levels of fasting glucose and triglycerides. There were no statistically significant differences for mineral levels. The MPO activity was reduced in the DM type 2 and Hypertension + DM type 2 groups and in cells. On the other hand, PSH and vitamin C levels were increased. The metformin has a protective effect in patients with DM type 2 against oxidative stress by reducing MPO activity and improving PSH and vitamin C antioxidant defenders. Further studies are needed to assess the biochemical mechanisms of metformin and how it can be used in a pharmacological therapeutic perspective against oxidative damage.

Cancer cases have increased significantly in Brazil and worldwide, with cutaneous melanoma (CM) being responsible for nearly 57,000 deaths in the world. Thus, this review article aims at exploring and proposed hypotheses with respect to the possibility that RA can be a promising and alternative compound to be used as an adjuvant in melanoma treatment, acting on purinergic signaling. The scarcity of articles evidencing the action of this compound in this signaling pathway requires further studies. Considering diverse evidence found in the literature, we hypothesize that RA can be an effective candidate for the treatment of CM acting as a modulating molecule of purinergic cellular pathway through P2X7 blocking, mitigating the Warburg effect, and as antagonic molecule of the P2Y12 receptor, reducing the formation of adhesive molecules that prevent adherence in tumor cells. In this way, our proposals for CM treatment based on targeting purinergic signaling permeate the integral practice, going from intracell to extracell. Undoubtedly, much is still to be discovered and elucidated about this promising compound, this paper being an interesting work baseline to support more research studies.

Major depressive disorder (MDD) etiology is still not completely understood, and many individuals resist the traditional treatments. Chronic exposure to stressful events can contribute to development and progression and be involved in biological changes underlying MDD. Among the biological mechanisms involved, inflammatory changes and oxidative balance are associated with MDD pathophysiology. Quetiapine, a second-generation antipsychotic, induces a better therapeutic response in individuals refractory to traditional treatments. The main objectives of this research were: To evaluate the effect of chronic mild stress (CMS) on depressive-like behaviors, oxidative stress, and inflammation in adult rats; to evaluate the possible antidepressant, antioxidant and anti-inflammatory effects of quetiapine. The animals were submitted to CMS protocols. At the end of the CMS, the animals were submitted to a chronic treatment for 14 days with the following drugs: quetiapine, imipramine, and escitalopram. At the end of the treatments, the animals were evaluated in the open field tests, anhedonia (splash test), and forced swimming. The animals were euthanized after the behavioral tests, and serum samples were collected. Myeloperoxidase (MPO) activity and interleukin-6 levels were analyzed. CMS induced an increase in depressive-like behaviors, and quetiapine significantly reduced these behaviors. MPO activity and IL-6 levels increased in the serum of animals submitted to CMS. Quetiapine significantly reduced MPO activity and IL-6 levels. These results corroborate other evidence, indicating that chronic stress is a relevant phenomenon in the etiology of depression and suggesting that quetiapine induces an antidepressant effect because it reduces oxidative and inflammatory mechanisms.

Background: despite limited long-term survival, kidney transplantation is the best form of renal replacement therapy for terminal disease patients. Components of extracellular purinergic signaling plays a fundamental role on inflammation and immune response related to organ transplantation. They could be alternative targets to avoid graft rejection. Materials and Methods: The hydrolysis of ATP, ADP and AMP nucleotides was analyzed in both lymphocytes and platelets, as well as the quantification of ATP and ADA activity. A sample of 30 patients who underwent kidney transplants was obtained, of which 15 had a transplant time of less than one year (acute response) and 15 had a transplant time between one and three years (chronic response). Results: In the group with transplantation time between one and three years, it was possible to identify a significant decrease in the amount of ATP, increase in ATP hydrolysis in platelets, decrease in AMP hydrolysis and increase in ADA activity, also in platelets. In the lymphocyte sample, there was a significant reduction in ADA activity as well as a decrease in the amount of ATP. Conclusions: From the data obtained in the study, it can be inferred that adenosine can reduce pro-inflammatory cytokines, providing greater graft survival and reducing the intensity of graft-versus-host disease. ATP signaling exerts inflammatory effects and modulates the purinergic signaling cascade, offering new avenues for drug therapies to combat chronic graft rejection.

Eye diseases have a negative impact on the eyesight quality of the world population. The age-related macular degeneration (AMD) draws special attention since it is a chronic disorder characterized ...

Graphical abstract The virus “acute respiratory syndrome coronavirus 2” (SARS-CoV-2) is the etiologic agent of coronavirus disease 2019 (COVID-19), initially responsible for an outbreak of pneumonia in Wuhan, China, which, due to the high level of contagion and dissemination, has become a pandemic. The clinical picture varies from mild to critical cases; however, all of these signs already show neurological problems, from sensory loss to neurological diseases. Thus, patients with multiple sclerosis (MS) infected with the new coronavirus are more likely to develop severe conditions; in addition to worsening the disease, this is due to the high level of pro-inflammatory cytokines, which is closely associated with increased mortality both in COVID-19 and MS. This increase is uncontrolled and exaggerated, characterizing the cytokine storm, so a possible therapy for this neuronal inflammation is the modulation of the cholinergic anti-inflammatory pathway, since acetylcholine (ACh) acts to reduce pro-inflammatory cytokines and acts directly on the brain for being released by cholinergic neurons, as well as acting on other cells such as immune and blood cells. In addition, due to tissue damage, there is an exacerbated release of adenosine triphosphate (ATP), potentiating the inflammatory process and activating purinergic receptors which act directly on neuroinflammation and positively modulate the inflammatory cycle. Associated with this, in neurological pathologies, there is greater expression of P2X7 in the cells of the microglia, which positively activates the immune inflammatory response. Thus, the administration of blockers of this receptor can act in conjunction with the action of ACh in the anticholinergic inflammatory pathway. Finally, there will be a reduction in the cytokine storm and triggered hyperinflammation, as well as the level of mortality in patients with multiple sclerosis infected with SARS-CoV-2 and the development of possible neurological damage.

Cutaneous melanoma is an aggressive and difficult-to-treat disease that has rapidly grown worldwide. The pharmacotherapy available in so many cases results in low response and undesirable side effects, which impair the life quality of those affected. Several studies have been shown that the purinergic system is involved in cancer context, such as in cutaneous melanoma. With technological advances, several bioactive compounds from nature are studied and presented as promising adjuvant therapies against cancer, as phenolic compounds and related action by purinergic system modulations. Thus, phenolic compounds such as rosmarinic acid, resveratrol, tannic acid, as well as vitamin D may be promising substances in a therapeutic perspective to treat cutaneous melanoma via purinergic system pathway. More research needs to be done to open up new horizons in the treatment of melanoma by the purinergic signaling.

BACKGROUND AND METHODS Essential arterial hypertension triggers a chronic inflammatory process that seems to be linked to purinergic signaling. Physical exercise exhibit anti-inflammatory properties and is able to modulates purinergic system. The aim of this study was to evaluate the effect of 6 months of resistance training on inflammatory markers, purinergic system components, hemodynamic and anthropometric parameters in hypertensive woman. METHODS A total of 31 hypertensive group and 28 normotensive (control group) middle-aged sedentary women were submitted to 6 months of resistance training. All measurements and blood collection were carried out before (pretest), after 3 months and after 6 months (posttest) of training. Purinergic enzymes [nucleoside triphosphate diphosphohydrolase (NTPDase) and adenosine deaminase] were assessed in lymphocytes; IL-6, IL-10, ATP and C-reactive protein levels were measured in serum. RESULTS Six months of resistance training was able to significantly reduce blood pressure (BP), IL-6, C-reactive protein, ATP levels as well as NTPDase and adenosine deaminase activities in hypertensive group. Physical training was also able to increase IL-10 levels in hypertensive group. A positive correlation was found between BP, enzyme activities and levels of ATP and IL-6. A negative correlation was found between BP and IL-10. Positive correlation was found between NTPDase and IL-6 levels (P

In this study, phytochemical profiling, and antidiabetic, antitumoral and cytotoxic potential of aqueous extracts of leaves of red variety of

Head and neck cancer (HNC) comprises a spectrum of neoplasms that affect the upper aerodigestive tract and are the sixth most common cancers worldwide. Individuals with HNC exhibit various symptoms and metabolic changes, including immune alterations and alterations of the purinergic pathway, which may signal worse outcomes. Therefore, the purpose of this research was to measure the activity of purinergic ectoenzymes and interleukins in patients with HNC, oral cavity cancer, and larynx cancer.We recruited 32 patients and 33 healthy control subjects and performed the laboratory analyses. We identified dysregulation in the purinergic signaling pathway characterized by an increase in adenosine triphosphate (ATP) and adenosine monophosphate (AMP) hydrolysis and a decrease in the deamination of adenosine to inosine in these cancers (p 0.05). These alterations were likely caused by increased activity of the ectoenzymes E-NTPDase and ecto-5'-nucleotidase and reduced adenosine deaminase activity. This dysregulation was associated with immune alterations, increased levels of IL-10, and decreased myeloperoxidase activity (p 0.05), suggesting immunosuppression in these patients and suggesting possible accumulation of adenosine in the extracellular environment.Adenosine is a potent immunosuppressive molecule associated with tumor progression and immune evasion. Our findings suggest a relationship between extracellular purines and the development and progression of the tumor microenvironment and poor outcomes. These findings increase the understanding of biological mechanisms related to HNC and demonstrate that these components are potential diagnostic markers and therapeutic targets for future management strategies and improvement in the quality of life.

In this study, phytochemical profiling, cytotoxic potential, antitumoral activity, and α-amylase and α-glucosidase inhibition capacity of extracts of seed and pulp of Eugenia uniflora L. fruits were investigated. The extracts were obtained using a cellulase complex and the phenolic compounds were quantified. The cytotoxic potential and antitumoral activity were evaluated using peripheral blood mononuclear cells and melanoma-type tumor cells, respectively. The α-amylase and α-glucosidase inhibition capacity was determined. For all extracts, the compounds identified and quantified were salicylic acid, protocatechuic acid, gallic acid and, myricitrin. For extract of pulp, ellagic and p-coumaric acids were also identified and quantified. The extracts do not show cytotoxicity in peripheral blood mononuclear cells. Extract of seed was able to decrease cell viability in melanoma-type tumor cells within 24 h of exposure. The concentration 5 µg mL−1 of extracts inhibited 7.73% of α-amylase and 15.34% of α-glucosidase. The Pitanga extracts presents substances with biological activities.

In this study, phytochemical profiling, and antidiabetic, antitumoral and cytotoxic potential of aqueous extracts of leaves of red variety of Psidium cattleianum Afzel. ex Sabine were investigated. The extracts were obtained using a cellulase complex. The total phenolic compounds (TPC) were determined, and the individual phenolic compounds were quantified by HPLC-ESI-MS/MS. For the TPC, the amounts varied from 85.91 to 106.33 mg EAG g−1. Eighteen compounds have been identified. The compounds with the highest concentrations were gallic acid, quercetin and protocatechuic acid. Antidiabetic activity was obtained through α-amylase and α-glucosidase inhibition tests. The extract inhibited 17.94% of α-amylase activity and 73.34% of α-glucosidase activity. The antitumoral activity in cells of cutaneous melanoma (SK-MEL-28) and the cytotoxic activity was determined in peripheral blood mononuclear cells (PBMC). The cellular migration was determined for cells SK-MEL-28. Antitumoral effects on cells SK-MEL-28 were observed and the absence of cytotoxicity on the PBMCs.

Made available in DSpace on 2022-04-29T08:37:32Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-12-01 Universidade Estadual Paulista (1) Background: Intermittent fasting is a nutrition practice in which individuals fast for several hours in a day, mainly with feeding time during the daylight hours. They seek to improve metabolic performance and cellular resistance to stress. In this study, we tested the fasting protocol to investigate the glycemic effect in a laparotomy perioperative period in diabetic rats and histopathologic findings. (2) Methods: The animals were diabetic-induced with alloxan. Two groups were set according to the feeding protocol: free food and intermittent fasting, whose rats could only eat 8 h in the daylight. Both groups were anesthetized, and a laparotomy was performed. We evaluated the glucose levels during the perioperative period, and we accessed organ histology seeking damage of kidney, bowel and liver after surgical trauma, and we evaluated the wound healing process. (3) Results: Glycemic levels were improved in the intermittent fasting group, especially in the post-operative period after laparotomy. Comparing both groups’ tubular damage showed interdependency with mice with worse glycemic level (Z = 2.3; p = 0.0215) and wound-healing parameters showed interdependency with rats with better glycemic status for neovascularization (Z = 2.2; p = 0.0273) and the presence of sebaceous and sweat gland in the healing process (Z = 2.30; p = 0.0215). (4) Conclusions: Intermittent fasting before surgery can be a tool to improve glycemic levels in diabetic rats, with improvement especially in the post-operative period. Anesthesia Department São Paulo State University (UNESP)-Botucatu Medical School Pharmacology and Histology Department Integrated Regional University (URI) Academic Coordination Biomedical Sciencies Department Federal University of Fronteira Sul Postgraduate Program in Biochemistry Department Federal University of Santa Catarina Anesthesia Department São Paulo State University (UNESP)-Botucatu

Um dos primeiros sistemas a sofrer o impacto do processo do envelhecimento fisiologico e o sistema sensorial e, particularmente, o visual, levando a deficiencia visual e ate mesmo a cegueira. As causas mais frequentes desse problema sao a catarata, a degeneracao macular relacionada a idade, o glaucoma, a retinopatia diabetica, entre outras doencas oculares. Desse modo, a qualidade de vida do idoso e afetada, comprometendo sua capacidade, independencia e autonomia. Assim, definiu-se como objetivo geral do trabalho avaliar o impacto das doencas oculares sobre a qualidade de vida dos idosos, alem das medidas preventivas relacionadas as deficiencias visuais. O metodo utilizado foi a revisao de literatura, por intermedio de pesquisa bibliografica. Os resultados demonstraram que doencas oculares afetam a qualidade de vida dos idosos, sendo responsaveis por limitar a mobilidade, levar a dependencia, falta de autonomia e capacidade, aumento a frequencia de acidentes, e diversos problemas causados pela falta de acuidade visual. Para prevenir esses problemas, varias campanhas foram criadas, apresentando resultado positivo na maioria destas campanhas.

EFEITO IN VITRO DO EXTRATO DE TUCUMA (ASTROCARYUM ACULEATUM) EM CELULAS MONONUCLEARES DE SANGUE PERIFERICO Felipe Ongaratto¹ Beatriz da Silva Rosa Bonadiman² Filomena Marafon³ Greicy Cristine Kosvoski4 Claudio do Carmo Chaves5 Claudia Maria Chaves6 Ivana Beatrice Mânica da Cruz7 Margarete Dulce Bagatini8 Eixo: educacao em saude. Introducao: O tucuma (Astrocaryum aculeatum) fruto nativo da Amazonia Brasileira, vem sendo estudado por apresentar uma serie de compostos bioativos, como, vitamina A, omega 3, 6 e 9, carotenoides, catequinas e quercetina que trariam beneficios para saude humana. Estudos previos demonstraram a capacidade antitumoral, anti-hiperglicemica e antimicrobiana desse fruto. Porem, ainda sao poucos os estudos com esse extrato. Objetivos: Dessa forma, o objetivo dessa pesquisa foi verificar o efeito do extrato hidroalcoolico de tucuma nas celulas mononucleares de sangue humano. Metodologia: Celulas mononucleares de sangue humano foram coletadas de voluntarios saudaveis (Comite de Etica no 822.782) e separadas por gradiente de densidade. O cultivo foi realizado com meio RPMI com 10% de soro fetal bovino e 1% de antifungico e antibiotico. As celulas foram mantidas em estufa com controle de temperatura e umidade. Apos duas horas de adaptacao a placa, as celulas foram tratadas com diferentes concentracoes do extrato de tucuma (5, 10, 50, 100 e 500 mg/mL) por 24 horas e realizados os testes de viabilidade celular (MTT). Para as analises de estresse oxidativo (mielopexosidase, oxido nitrico, substâncias reativas ao acido tiobarbiturico (TBARS), tiois nao proteicos (NPSH) e tiois proteicos (PSH) foram utilizadas as concentracoes de (10, 50, 100ug/mL). Os dados foram expressos como porcentagem do grupo controle e analisados estatisticamente com analise unidirecional de variância, seguida do teste post hoc de Tukey, utilizando o software Graphpad Prism versao 5.0 (Graphpad Prism Software Company, 2014). Resultados com p≤0,05 foram considerados estatisticamente significativos. Resultados e Discussao: Os resultados desse estudo demonstraram que todas as concentracoes do extrato de tucuma foram capazes de melhorar a viabilidade celular, estimulando a proliferacao das celulas (p

Melanoma is a type of skin cancer originated by the malignant transformation of melanocytes. Increasing incidence and mortality require efforts focused on studies and research about this cancer. Its microenvironment is rich in extracellular ATP, but there are no studies evaluating the ectonucleotidases and ATP effects on tumor-derived melanoma cells with known amounts of ATP. This way, the objective of this work was to evaluate the purinergic signaling in the pathophysiology of in vivo melanoma and the in vitro effects of ATP signaling. We found increased and effective extracellular ATP hydrolysis in platelets and a significant decrease of extracellular ATP levels and adenosine hydrolysis. In addition, we cultured PBMCs of melanoma patients and used ATP salt with specific concentrations to evaluate its signaling effects. The enzymatic activity analysis revealed that even with higher ATP doses cells metabolize adenine nucleotides less efficiently, and present low ATP, ADP and AMP hydrolytic activity in CM compared to CT cells. In summary, we showed for the first time important data about the purinergic signaling in the pathophysiology of melanoma and ATP signaling exercising immunosuppressive effects. Therefore, as already shown for other tumors, the purinergic signaling should be considered a potential target for melanoma management and treatment and could offer novel therapeutic prospects.

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.

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. 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. 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.