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Cutaneous melanoma (CM) is an aggressive and metastatic tumor, resulting in high mortality rates. Despite significant advances in therapeutics, the available treatments still require improvements. Thus, purinergic signaling emerged as a potential pathway to cancer therapy due to its involvement in cell communication, proliferation, differentiation, and apoptosis. In addition, due to safety and acceptable clinical tolerability, carotenoids from microalgae have been investigated as adjuvants in anti-melanoma therapy. Then, this work aimed to investigate the in vitro anti-melanogenic effect of carotenoid extract (CA) and total biomass (BM) of the Scenedesmus obliquus microalgae on two cutaneous melanoma cell lines (A375 and B16F10). Cells were cultivated under ideal conditions and treated with 10, 25, 50, and 100 μM of CA or BM for 24 h. The effects of the compounds on viability, oxidant status, and purinergic signaling were verified. The IC50 cell viability results showed that CA and BM decreased B16F10 viability at 24.29 μM and 74.85 μM, respectively and decreased A375 viability at 73.93 μM and 127.80 μM, respectively. Carotenoid treatment for 24 h in B16F10 and A375 cells increased the release of reactive oxygen species compared to the control. In addition, CA and BM isolated or combined with cisplatin chemotherapy (CIS) modulated the purinergic system in B16F10 and A375 cell lines through P2X7, A2AR, CD39, and 5'-nucleotidase. They led to cell apoptosis and immunoregulation by activating A2A receptors and CD73 inhibition. The results disclose that CA and BM from Scenedesmus obliquus exhibit an anti-melanogenic effect, inhibiting melanoma cell growth.

Tannic acid (TA) exhibits low bioavailability in the gastrointestinal tract, limiting its benefits due to small amounts reaching the CNS. Thus, the objective of this study was to develop zein capsules and fibers by electrospraying/electrospinning for encapsulation of TA. Polymeric solutions were evaluated by electrical conductivity, density, and viscosity. In zein capsules, up to 2 % TA was added, and in fibers, up to 1 % TA was added. Zein capsule and fiber with TA were evaluated by morphology, size distribution, encapsulation efficiency, thermal and thermogravimetric properties, and functional groups. Zein capsule with 1.5 % TA was evaluated in astrocyte culture for cytotoxicity and antioxidant activity. TA zein capsules and fibers exhibited high encapsulation efficiency and homogeneous morphology. TA encapsulated in zein presented higher thermal stability than free TA. TA zein capsule did not present toxicity and elicited antioxidant action in lipopolysaccharide-induced astrocyte culture. Capsules and fibers were successfully produced by electrospraying/electrospinning techniques., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the study reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: Our aim in this study was to identify predictors for diabetes among the characteristics of the glycemic curve and glycated hemoglobin (A1C) in healthy, young adults., Methods: We used a cross-sectional study to establish predictors for diabetes based on earlier studies and evaluated occurrence of the condition in 81 healthy, young adult subjects. These volunteers underwent analysis of fasting plasma glucose, oral glucose tolerance test plasma glucose, A1C, and inflammatory markers (leukocytes, monocytes, and C-reactive protein). The nonparametric Mann-Whitney U test, Fisher's exact test, chi-square test, Kruskal-Wallis test, and multiple-comparisons test were used to analyze the data., Results: We studied 2 age groups, homogeneous in terms of family history of diabetes: one group ranged in age from ≥18 to <28 years (median 20 years; body mass index [BMI] 24 kg/m 2 ) and the other group ranged in age from ≥28 to <45 years (median 35 years; BMI 24 kg/m 2 ). The older group had a higher incidence of predictors (p=0.0005) and was associated with the predictors 30-minute blood glucose ≥164 mg/dL (p=0.0190), 60-minute blood glucose ≥125 mg/dL (p=0.0346), and A1C ≥5.5% (p=0.0162), with a monophasic glycemic curve (p=0.007). The younger group was associated with the 2-hour plasma glucose predictor ≥140 mg/dL (p=0.014). All subjects had fasting glucose in the normal range., Conclusions: Healthy, young adults may already have predictors of diabetes, identified mainly by aspects of the glycemic curve and A1C, but at more modest levels than those with prediabetes., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Chagas Disease (CD) affects around eight million people worldwide. It is considered a neglected disease that presents few treatment options with efficacy only in the acute phase. Nanoparticles have many positive qualities for treating parasite infections and may be effectively and widely employed in clinical medicine. This research aimed to evaluate the nanoencapsulated benznidazole treatment in animals experimentally infected with Trypanosoma cruzi. To analyze the treatment efficacy, we evaluated survival during thirty days, parasitemia, genotoxicity, and heart and liver histopathology. Thirty-five female Swiss mice were organized into seven groups characterizing a dose curve: A - Negative control (uninfected animals), B - Positive control (infected animals), C - Benznidazole (BNZ) 100 mg/kg (infected animals), D - 5 mg/kg Benznidazole nanocapsules (NBNZ) (infected animals), E - 10 mg/kg Benznidazole nanocapsules (infected animals), F - 15 mg/kg Benznidazole nanocapsules (infected animals), G - 20 mg/kg Benznidazole nanocapsules (infected animals). The animals were infected with the Y strain of T. cruzi intraperitoneally. The treatment was administered for eight days by oral gavage. It was possible to observe that the treatment with the highest NBNZ dose presented efficacy similar to the standard benznidazole drug. The 20 mg/kg NBNZ dose was able to reduce parasitemia, increase survival, and drastically reduce heart and liver tissue damage compared to the 100 mg/kg BNZ dose. Moreover, it showed a lower DNA damage index than the BNZ treatment. In conclusion, the nanoencapsulation of BNZ promotes an improvement in parasite proliferation control with a five times smaller dose relative to the standard dose of free BNZ, thus demonstrating to be a potential innovative therapy for CD., Competing Interests: Declaration of competing interest The authors declared no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cancer and infectious diseases are among the leading causes of death in the world. Despite the diverse array of treatments available, challenges posed by resistance, side effects, high costs, and inaccessibility persist. In the Solanaceae plant family, few studies with Vassobia breviflora species relating to biological activity are known, but promising results have emerged. The phytochemicals present in the ethyl acetate fraction were obtained using ESI-MS-QTOF, and the antioxidants assays 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) radical capture (ABTS), plasma ferric reduction capacity (FRAP), and total antioxidant capacity (TAC). Cytotoxic activity was evaluated by MTT, Neutral Red, and lactate dehydrogenase (LDH) released. The production of reactive oxygen species, nitric oxide, and purinergic enzymes was also investigated. Antibacterial activity was measured through minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and antibiofilm activity, in addition to genotoxicity in plasmid DNA. Five major masses were identified D-glucopyranose II, allyl disulfide, γ-lactones, pharbilignoside, and one mass was not identified. V. breviflora exhibited relevant antioxidant and cytotoxic activity against the HeLa cell line and enhanced expression effect in modulation of purinergic signaling. Antibacterial activities in the assays in 7 ATCC strains and 8 multidrug-resistant clinical isolates were found. V. breviflora blocked biofilm formation in producing bacteria at the highest concentrations tested. However, there was no plasmid DNA cleavage at the concentrations tested. Data demonstrated that V. breviflora exhibited an antioxidant effect through several methods and proved to be a promising therapeutic alternative for use against tumor cells via purinergic signaling and multidrug-resistant microorganisms, presenting an anti-biofilm effect.

Neuroinflammation is an inflammatory process in the central nervous system (CNS), in addition to being one of the main features of Alzheimer's disease (AD) and Parkinson's disease (PD). Microglia are known for their immune functions and have multiple reactive phenotypes related to the types of stages involving neurodegenerative diseases. Depending on the state of activation of microglia in the CNS, it can be neuroprotective or neurotoxic. In this context, AD is a neurodegenerative and neuroinflammatory disease characterized by the deposition of beta-amyloid plaques, formation of fibrillar tangles of tau protein, and loss of neurons due to neurotoxic activation of microglia. However, PD is characterized by the loss of dopaminergic neurons in the substantia nigra and accumulation of alpha-synuclein in the cortical regions, spinal cord, and brain stem, which occurs by microglial activation, contributing to the neuroinflammatory process. In this aspect, the activation of microglia in both pathologies triggers high levels of inflammatory markers, such as interleukins, and causes the neuroinflammatory process of the diseases. Thus, physical exercise is pointed out as neuroprotective, as it can act to strengthen neurogenesis and reduce the inflammatory process. Therefore, the present review addresses the neuroprotective effect of microglia after different types of physical exercise protocols and evaluates the activity and effects of inflammatory and anti-inflammatory parameters and mechanisms of AD and PD. This review will discuss the anti-inflammatory effects of physical exercise through microglia activation with neuroprotective activity and the role of pro-and anti-inflammatory cytokines in AD and PD., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Both the cholinergic pathway and oxidative stress are important mechanisms involved in the pathogenesis of hypothyroidism, a condition characterized by low levels of thyroid hormone that predispose the patient to brain dysfunction. Phenolic compounds have numerous health benefits, including antioxidant activity. This study evaluates the preventive effects of resveratrol in the cholinergic system and redox status in rats with methimazole-induced hypothyroidism. Hypothyroidism increases acetylcholinesterase (AChE) activity and density in the cerebral cortex and hippocampus and decreases the α7 and M1 receptor densities in the hippocampus. Hypothyroidism also increases cellular levels of reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS), but reduces total thiol content, and catalase and superoxide dismutase activities in the serum. In the cerebral cortex and hippocampus, hypothyroidism increases the levels of ROS and nitrites. In this study, resveratrol (50 mg/kg) treatment prevents the observed increase in AChE in the cerebral cortex, and increases the protein levels of NeuN, a marker of mature neurons. Resveratrol also prevents changes in serum ROS levels and brain structure, as well as the levels of TBARS, total thiol content, and serum catalase enzyme activity. These collective findings suggest that resveratrol has a high antioxidant capacity and can restore hypothyroidism-triggered alterations related to neurotransmission. Thus, it is a promising agent for the prevention of brain damage resulting from hypothyroidism., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Thyroid hormones have essential roles in regulation of cellular functions, including the immune system. The purinergic signaling, activated through extracellular nucleotides and nucleosides has also strong implications in immune response regulation. Hypothyroidism may involve effects on the immune and purinergic systems. In view of that, we evaluated cytokines levels, their relation with the expression of purinergic enzymes and the effects of this condition on immune system cells from patients with post-thyroidectomy hypothyroidism. Increased IL6, IL10, IL17 and TNF-α levels as well as an increase in CD73 expression in lymphocytes were observed in patients' blood. Moreover, augmented myeloperoxidase activity, lipid peroxidation and thiolgroup production were observed in post-thyroidectomy hypothyroidism. In addition, proliferation and cell death of lymphocytes were enhanced when exposed to patients' serum. This study demonstrates that hypothyroidism is related to changes in the purinergic system, increased cytokines production and oxidative stress, which interfere in the cell life and signaling., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease. The present study investigated the effects of 50 and 100 mg/kg berberine (BRB) on recognition memory, oxidative stress, and purinergic neurotransmission, in a model of sporadic dementia of the Alzheimer's type induced by intracerebroventricular (ICV) injection of streptozotocin (STZ) in rats. Rats were submitted to ICV-STZ 3 mg/kg or saline, and 3 days later, were started on a treatment of BRB or saline for 21 days. The results demonstrated that BRB was effective in protecting against memory impairment, increased reactive oxygen species, and the subsequent increase in protein and lipid oxidation in the cerebral cortex and hippocampus, as well as δ-aminolevulinate dehydratase inhibition in the cerebral cortex. Moreover, the decrease in total thiols, and the reduced glutathione and glutathione S-transferase activity in the cerebral cortex and hippocampus of ICV-STZ rats, was prevented by BRB treatment. Besides an antioxidant effect, BRB treatment was capable of preventing decreases in ecto-nucleoside triphosphate diphosphohydrolase (NTPDase), 5'-nucleotidase (EC-5'-Nt), and adenosine deaminase (ADA) activities in synaptosomes of the cerebral cortex and hippocampus. Thus, our data suggest that BRB exerts a neuroprotective effect on recognition memory, as well as on oxidative stress and oxidative stress-related damage, such as dysfunction of the purinergic system. This suggests that BRB may act as a promising multipotent agent for the treatment of AD.

The present study evaluated the neuroprotective effects of one selenium-containing AZT derivative compound (S1073) in memory and learning impairment caused by Intracerebroventricular-streptozotocin (ICV-STZ). ICV-STZ in mice causes impairment of energy metabolism with oxidative damage and cholinergic dysfunction, and provides a relevant model for sporadic dementia of Alzheimer's type (AD). Acetylcolinesterase (AChE), Catalase (CAT), dichlorofluorescein oxidation (DCFH), TBARS and thiol content were measured. Swiss adult mice were pre-treated with S1073 [1 mmol/kg] (i.p.) and after 30 min of the injection received a bilateral dose of STZ [11.3 μmol/l]. After 8 days' STZ injection, we performed the behavioral experiments (Beaker test, Open field and Morris water maze task). ICV-STZ caused significant learning and memory impairments, which were significantly improved by S1073 pre-treatment. A significant increase in cerebral DFCH, TBARS levels and AChE activity and a disturbance in the memory and learning were observed in ICV-STZ injected animals. S1073 significantly ameliorated all alterations induced by ICV-STZ in mice. All these findings support the neuroprotective role of S1073 in mice model of Alzheimer's dementia-type induced by ICV-STZ, which may be associated with its antioxidant activity and/or with its inhibitory effect in brain AChE. In fact, in silico analysis indicated that S1073 may be an inhibitor of AChE., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Diabetes mellitus (DM) is characterised by hyperglycaemia associated with the increase of oxidative stress. Gallic acid has potent antioxidant properties. The aim of this study was to evaluate the effect of gallic acid on the biochemical, histological and oxidative stress parameters in the liver and kidney of diabetic rats. Male rats were divided in groups: control, gallic acid, diabetic and diabetic plus gallic acid. DM was induced in the animals by intraperitoneal injection of streptozotocin (65mg/kg). Gallic acid (30mg/kg) was administered orally for 21days. Our results showed an increase in reactive species levels and lipid peroxidation, and a decrease in activity of the enzymes superoxide dismutase and delta-aminolevulinic acid dehydratase in the liver and kidney of the diabetic animals (P<0.05). Gallic acid treatment showed protective effects in these parameters evaluated, and also prevented a decrease in the activity of catalase and glutathione S-transferase, and vitamin C levels in the liver of diabetic rats. In addition, gallic acid reduced the number of nuclei and increased the area of the core in hepatic tissue, and increased the glomerular area in renal tissue. These results indicate that gallic acid can protect against oxidative stress-induced damage in the diabetic state., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Context: This study aims to explore the potential of new inflammatory markers for improving the challenging diagnosis of acute appendicitis (AA)., Methods: Levels of IL-1, IL-6, IL-8, IL-10, CRP, INF-γ, and TNF-α in serum were measured in 73 patients with AA. Oxidative stress and antioxidant enzymes were analyzed., Results: Serum levels of interleukins, TNF-α, and INF-γ were significantly elevated in patients with appendicitis (p < 0.0001), except for IL-10, which presented decreased levels. There were no significant differences in SOD (p = 0.29), CAT (p = 0.19), or TBARS levels (p = 0.18), whereas protein carbonyls presented significant increase (p < 0.0001)., Conclusion: Evaluating these biomarkers could aid in diagnosing AA.

Breast cancer is the most frequent neoplasm affecting women worldwide. Some of the recommended treatments involve chemotherapy whose toxic effects include leukopenia and neutropenia. This study assessed the effectiveness of Uncaria tomentosa (Ut) in reducing the adverse effects of chemotherapy through a randomized clinical trial. Patients with Invasive Ductal Carcinoma-Stage II, who underwent a treatment regimen known as FAC (Fluorouracil, Doxorubicin, Cyclophosphamide), were divided into two groups: the UtCa received chemotherapy plus 300 mg dry Ut extract per day and the Ca group that only received chemotherapy and served as the control experiment. Blood samples were collected before each one of the six chemotherapy cycles and blood counts, immunological parameters, antioxidant enzymes, and oxidative stress were analyzed. Uncaria tomentosa reduced the neutropenia caused by chemotherapy and was also able to restore cellular DNA damage. We concluded that Ut is an effective adjuvant treatment for breast cancer.

In a previous work based on popular belief, Campomanesia xanthocarpa Berg., popularly known as "guavirova", showed to have a potential effect in the control of a number of conditions associated with cardiovascular diseases. The aim of the present work was to investigate the effects of C. xanthocarpa extract (CXE) on antiplatelet, antithrombotic and fibrinolytic activities in mice and in human blood. Mice were treated orally for 5 days with CXE or acetylsalicylic acid and at the end of the treatment period animals were challenged for bleeding, acute thromboembolism and ulcerogenic activity. In addition, we have assessed the prothrombin time and activated partial thromboplastin time (aPTT) after oral administration. In in vitro assays, antiplatelet effects of CXE was evaluated on platelet aggregation, and fibrinolytic activity of the extract was observed by mice or human artificial blood clot degradation. Platelet citotoxicity of the extract was also determined by the LDH assay. Results demonstrated that CXE has a significant protective effect on thrombosis. It also inhibits platelet aggregation without demonstrating cytotoxicity on platelets. CXE slightly prolonged aPTT and showed no ulcerogenic activity after oral administration. In addition, CXE showed a fibrinolytic activity. Thus, C. xanthocarpa showed antiplatelet, antithrombotic and fibrinolytic activities in mice.

Methods for the isolation of peripheral blood mononuclear cells (PBMCs) and human lung mononuclear cells (LMCs) have been proposed previously. This study describes a method that allows the separation of lymphocyte-rich LMCs from rats. Trypan blue was applied to determine cell viability. White blood cell and differential cell counts were also performed. Relationships between nucleoside triphosphate diphosphohydrolase (NTPDase, EC 3.6.1.5) activities expressed in milligrams of protein, millions of cells, and millions of viable cells were examined as linear correlations. The lung tissue yielded 82.46% lymphocytes, 8.6% macrophages, 2.20% monocytes, and 1.27% polymorphonuclear cells (PMNs). In LMCs, a very strong correlation was observed as follows: between NTPDase activity, as determined using ATP or ADP as a substrate, expressed in milligrams of protein and that expressed in millions of cells (r ≥ 0.91), between that expressed in milligrams of protein and that expressed in millions of viable cells (r ≥ 0.91), and between that expressed in millions of cells and that expressed in millions of viable cells (r ≥ 0.98). Based on our results, we affirm that NTPDase activity could be expressed in millions of viable cells, millions of cells, or milligrams of protein., (2010 Elsevier Inc. All rights reserved.)

The objective of the present study was to investigate the effect of the administration of resveratrol (RV) on memory and on acetylcholinesterase (AChE) activity in the cerebral cortex, hippocampus, striatum, hypothalamus, cerebellum and blood in streptozotocin-induced diabetic rats. The animals were divided into six groups (n=6-13): Control/saline; Control/RV 10 mg/kg; Control/RV 20 mg/kg; Diabetic/saline; Diabetic/RV 10 mg/kg; Diabetic/RV 20 mg/kg. One day after 30 days of treatment with resveratrol the animals were submitted to behavioral tests and then submitted to euthanasia and the brain structures and blood were collected. The results showed a decrease in step-down latency in diabetic/saline group. Resveratrol (10 and 20 mg/kg) prevented the impairment of memory induced by diabetes. In the open field test, no significant differences were observed between the groups. In relation to AChE activity, a significant increase in diabetic/saline group (P<0.05) was observed in all brain structures compared to control/saline group. However, AChE activity decreased significantly in control/RV10 and control/RV20 (P<0.05) groups in cerebral cortex, hippocampus and striatum, while no significant differences were observed in diabetic/RV10 and diabetic/RV20 groups in all brain structures compared to control/saline group. Blood AChE activity increased significantly in diabetic/saline group (P<0.05) decreased in control/RV10, control/RV20 and diabetic/RV20 groups (P<0.05) compared to control/saline group. In conclusion, the present findings showed that treatment with resveratrol prevents the increase in AChE activity and consequently memory impairment in diabetic rats, demonstrating that this compound can modulate cholinergic neurotransmission and consequently improve cognition.

Objective: Ectonucleotide pyrophosphatase/phosphodiesterase (E-NPP) and adenosine deaminase (ADA) activities, in the platelets and serum, were examined in patients with uterine cervix neoplasia without treatment as well as in patients treated by conization or radiotherapy (RTX)., Design and Methods: The patients were divided based on the amount of time from the end of the treatments until the day of the blood sampling. Groups I (n=19) (conization) and III (n=11) (radiotherapy) (treated from one to five years earlier), groups II (n=19) (conization) and IV (n=16) (radiotherapy) (treated recently; up to three months earlier) and the non-treated group (cancer) (n=7)., Results: E-NPP and ADA in the platelets and E-NPP in the serum were decreased in all the treated groups in relation to the control and non-treated groups, while ADA in the serum was decreased only in the conization groups in relation to them. In group II, E-NPP and ADA, in the platelets, were increased in relation to group IV., Conclusion: The tendency of reduction for E-NPP and ADA indicates that they may act together to control nucleotide levels and it may also be speculated that surgery causes greater platelet activation contributing to the changes seen in the conization groups. In this sense, platelets seem to be more sensitive than serum.

Adenosine, an endogenous neuroprotective agent, can be produced in the synaptic cleft from adenosine triphosphate (ATP) hydrolysis via the concerted action of two enzymes: ATP diphosphohydrolase and 5'-nucleotidase. The aim of the present study was to investigate such enzymatic activities in the hippocampus of rats subjected to single (2- or 10-minute) or double (2+10 minute, with a 24-hour interval in between, named preconditioned group) ischemic episodes. Ischemia was produced by four-vessel occlusion method. Histological analysis showed no cell death in 2-minute ischemia, and up to 90% of pyramidal CA(1) cell loss in the 10-minute ischemic group. As predicted, double ischemic rats displayed a significant cytoprotective effect (around 60%). Preconditioned rats presented a delayed enhancement in ATP diphosphohydrolase activity (for ATP and adenosine diphosphate hydrolysis) after 48 hours of reperfusion. 5'-nucleotidase activity was increased immediately after ischemic insult (for all groups) and after a late reperfusion period (48 hours). We suggest that preconditioning causes delayed changes in enzymatic activities that would conceivably lead to increased adenosine production. This effect could be related to cytoprotection seen in preconditioned rats.