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By uncoupling oxidative phosphorylation, 2,4-dinitrophenol (DNP) attenuates reactive oxygen species (ROS) biosynthesis, which are known to aggravate infectious myocarditis in Chagas disease. Thus, the impact of DNP-based chemotherapy on Trypanosoma cruzi-induced acute myocarditis was investigated. C56BL/6 mice uninfected and infected untreated and treated daily with 100 mg/kg benznidazole (Bz, reference drug), 5 and 10 mg/kg DNP by gavage for 11 days after confirmation of T. cruzi infection were investigated. Twenty-four hours ​after the last treatment, the animals were euthanized and the heart was collected for microstructural, immunological and biochemical analyses. T. cruzi inoculation induced systemic inflammation (e.g., cytokines and anti-T. cruzi IgG upregulation), cardiac infection (T. cruzi DNA), oxidative stress, inflammatory infiltrate and microstructural myocardial damage in untreated mice. DNP treatment aggravated heart infection and microstructural damage, which were markedly attenuated by Bz. DNP (10 mg/kg) was also effective in attenuating ROS (total ROS, H 2 O 2 , and O 2 - ), nitric oxide (NO), lipid (malondialdehyde - MDA) and protein (protein carbonyl - PCn) oxidation, TNF, IFN-γ, IL-10, and MCP-1/CCL2, anti-T. cruzi IgG, cardiac troponin I levels, as well as inflammatory infiltrate and cardiac damage in T. cruzi-infected mice. Our findings indicate that DNP aggravated heart infection and microstructural cardiomyocytes damage in infected mice. These responses were related to the antioxidant and anti-inflammatory properties of DNP, which favors infection by weakening the pro-oxidant and pro-inflammatory protective mechanisms of the infected host. Conversely, Bz-induced cardioprotective effects combined effective anti-inflammatory and antiparasitic responses, which protect against heart infection, oxidative stress, and microstructural damage in Chagas disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Pfaffia glomerata (Spreng.) Pedersen has traditionally been used as a tonic and a stimulant by the Brazilian population. It shows higher biomass accumulation and production of secondary compounds, such as the phytosterol 20-hydroxyecdysone., Aims: The present study aimed to evaluate the effects of the hydroalcoholic extract of the root of tetraploid P. glomerata (BGEt) on testicular parenchyma, and its implications on fertility., Material and Methods: Adult Swiss mice were divided as: control (water) and sildenafil citrate (7 mg/kg), BGEt at 100, 200, and 400 mg/kg, and BGEtD 200 mg/kg (treated with BGE every three days). Males (n = 4/group) were mated with normal untreated adult females to assess fertility rates, while other animals (n = 6/group) were euthanized for testis, epididymis, and oxidative stress analyses., Results: Increase in tubule diameter and epithelium height in the discontinuous group, in addition to an increase in the proportion of tubules with moderate pathologies was observed. The pre-implantation loss was lower in all treated groups. The post-implantation loss was significantly increased in all treated groups, except for the lowest BGEt dose. BGEt intake caused a decrease in daily sperm production, along with the number and quality of sperm in the epididymis. Changes were observed in protein carbonylation and hydrogen peroxide and nitric oxide levels, characterizing oxidative stress., Conclusions: The hydroalcoholic extract of P. glomerata tetraploid altered sperm and testicular parameters, compromising embryonic development after implantation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

From a systematic review framework, we analysed the clinical evidence on the effectiveness and safety of monotherapy and combination chemotherapy for Chagas disease (ChD) treatment. The research protocol was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and patient, intervention, comparison and outcome strategy. Only randomized controlled trials (RCT) were retrieved from Embase, Medline, Scopus and Web of Science databases. Diagnostic tools, treatment protocols, seroconversion rates and adverse events were investigated. Fifteen RCT mainly concentrated in endemic countries were identified. ChD diagnosis was mainly based on haemagglutination, immunofluorescence, enzyme-linked immunosorbent assay and polymerase chain reaction. Benznidazole (BNZ), nifurtimox, fosravuconazole, posaconazole, allopurinol and thioctic acid were the identified drugs. The best negative seroconversion results (100, 96, 94 and 91.3%) were, respectively, based on BNZ (5 mg kg day −1 , 200 mg day −1 , 150 mg day −1 and 2.5 mg kg −1 ) administration for 60 days. Negative seroconversion was not achieved with allopurinol (300 mg day −1 for 60 days). Adverse reactions ranged from 5 to 73% in patients receiving antiparasitic chemotherapy. Treatment discontinuation (1.5–57%) was mainly associated with gastrointestinal, cutaneous and neurological manifestations. Current RCT-based evidence indicates that BNZ is the most viable option for ChD treatment. However, new protocols need to be developed to mitigate side effects and increase patient adherence to antiparasitic chemotherapy. Therefore, shorter regimens, lower concentrations and treatments combining BNZ with posaconazole, fosravuconazole or ravuconazole may be viable to ensure comparable efficacy to BZN-based monotherapy, contributing to reduce dose- and time-dependent toxicity reactions.

Deltamethrin (DTM) is a synthetic pyrethroid widely used in the cultivation and management of several crops due to its insecticidal action. Application to crops of pyrethroids such as DTM can result in the exposure of water and fruit consumed by fruit bats having a high pyrethroid content which may be harmful. Therefore the objective of this study was to evaluate the effects of short-term oral exposure of the fruit-eating bats (Artibeus lituratus) to two concentrations of DTM (0.02 and 0.04 mg/kg of papaya) on histopathology of the intestine, liver and kidney. The intestine of the animals exposed to both concentrations showed inflammatory infiltrate, degeneration, necrosis and goblet cell hyperplasia as the most frequent pathologies. Besides, the acid mucins showed an increase in the frequency of non-viable cells. The liver showed hepatocyte vacuolizatio and nuclear enlargement, as well as inflammatory infiltrate and steatosis. The kidneys of the exposed animals showed and inflammatory infiltrate, benign nephrosclerosis, vacuolization and necrosis. Also, DTM reduced nitric oxide synthesis, decreased glomerular diameter and increased glycogen percentage in the proximal tubules. Our results suggest that acute exposure to DTM at low concentrations has the potential to induce pronounced histopathological changes in vital organs, such as intestine, liver and kidney of fruit-eating bats., (© 2022 Company of the International Journal of Experimental Pathology (CIJEP).)

Eugenol is the main constituent of clove extract. It is a remarkably versatile molecule incorporated as a functional ingredient in several food products and widely applied in the pharmaceutical industry. Men consume natural products enriched with eugenol for treating sexual disorders and using as aphrodisiacs. Nevertheless, there is no information about the impact of eugenol intake on the reproductive parameters of healthy males. Therefore, we provided 10, 20, and 40 mg kg -1 pure eugenol to adult Wistar rats for 60 days. Testis, epididymis, and spermatozoa were analyzed under microscopic, biochemical, and functional approaches. This phenolic compound did not alter testicular and epididymal biometry and microscopy. However, 20 and 40 mg kg -1 eugenol reduced serum testosterone levels. The highest dose altered lactate and glucose concentrations in the epididymis. All the eugenol concentrations diminished CAT activity and MDA levels in the testis and increased FRAP and CAT activity in the epididymis. Epididymal sperm from rats receiving 10, 20, and 40 mg kg -1 eugenol presented high Ca 2+ ATPase activity and low motility. In conclusion, eugenol at low and high doses negatively impacted the competence of epididymal sperm and modified oxidative parameters in male organs, with no influence on their microscopy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Eugenol is a phenolic compound found in clove extract and extensively used in traditional medicine. It is unclear whether its intake can cause positive or negative effects on liver morphology and physiology in healthy individuals. Thus, we aimed to evaluate liver parameters of rats treated with 10, 20, and 40 mg kg -1 eugenol. After 60 days of treatment, liver samples were collected and analyzed by biometric, histological, biochemical, and oxidative analyses. Our results showed that 10, 20, and 40 mg kg -1 eugenol did not alter body and liver weights, serum and hepatic ALT levels and catalase, glutathione-s-transferase, total, Ca 2+ , and Mg 2+ ATPases activities in treated animals. However, 20 and 40 mg kg -1 eugenol reduced Na + /K + ATPase pump activity and blood glucose levels. They also increased hepatic glycogen content, superoxide dismutase activity, ferric reducing antioxidant power, and nitric oxide and malondialdehyde levels. Still, 20 and 40 mg kg -1 eugenol caused structural and functional damage to the liver tissue of eugenol-treated rats. We concluded that 10 mg kg -1 eugenol is a safe dose for consumption in long-term treatment for rats. Doses higher than 20 mg kg -1 lead to hepatic damage that can impair vital processes of liver functionality., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Athenaea velutina is a promising Brazilian shrub with cytotoxic and antimigratory properties against cancer cells. However, the mechanism of induction of cancer cell death and the compounds involved remain unknown. To ascertain these bioactive compounds, bioassay-guided fractionation was performed, alongside the appropriate in vitro tests. A withanolide-rich fraction (F Av _5) from the dichloromethane extract increased cytotoxic activity by 1.5-fold (IC 50  = 2.1 µg/mL). Fourteen withanolide steroids were tentatively identified for the first time for this species by mass spectrometry coupled to liquid chromatography (LC MS/MS), including withanolide A, aurelianolide A, and aurelianolide B. F Av _5 significantly decreased cell proliferation, migration, and invasion with a selectivity index greater than 8 for B16F10 cells. Furthermore, flow cytometry with annexin V fluorescein isothiocyanate/propidium iodide (V-FITC/PI) staining showed F Av _5 to promote cell cycle arrest at the G0/G1-phase as well as apoptotic cell death. Overall, these findings highlight A. velutina as a source of withanolide-steroids that inhibit cancer cell proliferation through apoptosis and cell cycle blockade mechanisms. Details on the geographic distribution of A. velutina and species conservation strategies have also been highlighted., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Aims: Plastic particles (PP) pollution is a global environmental concern. Although the reproductive toxicity of PP is primarily understood for invertebrates, the evidence for mammals is still fragmented. We used a systematic review framework to investigate the reproductive impact of microplastics and nanoplastics (MNP) on mammals., Materials and Methods: Research records were screened from Embase, Medline, Scopus and Web of Science. Twelve original papers were identified and reviewed. Immunological, oxidative and morphofunctional outcomes, and the risk of bias in all studies reviewed were analyzed., Key Findings: These studies indicated that PP can accumulate in the gonads, triggering seminiferous degeneration, Sertoli cells death, blood-testis barrier disruption, sperm degeneration, malformation, reduced number and mobility, ovarian cysts, reduced follicular growth and granulosa cells death. Gonadal damage was associated with upregulation of prooxidant mediators (oxygen reactive species, lipid and DNA oxidation), cell death, proinflammatory molecular pathways and cytokines, as well as inhibition of enzymatic and non-enzymatic antioxidant defense mechanisms. Spermatogenesis, folliculogenesis, testosterone, progesterone and estrogen levels were also impaired in PP-treated animals, which were potentially associated with down-regulation of molecules involved in germ cells microstructural organization (occludin, N-cadherin, β-catenin and connexin 43) and steroidogenesis, such as hydroxysteroid dehydrogenases, steroidogenic acute regulatory proteins, follicle stimulating and luteinizing hormones. Selection, performance and detection bias were the main limitations identified., Significance: Current evidence indicates that PP can induce dose-dependent microstructural and functional gonadal damage, which is orchestrated by pro-oxidant and pro-inflammatory mechanisms that disrupt genes, molecular effectors, and hormones that control spermatogenesis and folliculogenesis., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Melanoma is the most aggressive skin cancer, and its incidence has continued to rise during the past decades. Conventional treatments present severe side effects in cancer patients, and melanoma can be refractory to commonly used anticancer drugs, which justify the efforts to find new potential anti-melanoma drugs. An alternative to promote the discovery of new pharmacological substances would be modifying chemical groups from a bioactive compound. Here we describe the synthesis of seventeen compounds derived from cinnamic acid and their bioactivity evaluation against melanoma cells. The compound phenyl 2,3-dibromo-3-phenylpropanoate (3q) was the most effective against murine B16-F10 cells, as observed in cytotoxicity and cell migration assays. Simultaneously, this compound showed low cytotoxic activity on non-tumor cells. At the highest concentration, the compound 3q was able to trigger apoptosis, whereas, at lower concentrations, it affected the cell cycle and melanoma cell proliferation. Furthermore, cinnamate 3q impaired cell invasion, adhesion, colonization, and actin polymerization. In conclusion, these results highlight the antiproliferative and antimetastatic potential of cinnamic acid derivatives on melanoma., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Considering the efficacy of rapamycin in increasing lifespan and healthspan, attenuating the aging-dependent immunological decline, we compared the evolution of Trypanosoma cruzi infection and acute myocarditis in young and elderly mice untreated and chronically treated with this drug. Five groups were investigated: young uninfected and infected, elderly uninfected and infected with Trypanosoma cruzi untreated and treated with rapamycin (4 mg/kg every 3 days) from the 8th to the 96th week of age. Seven days after the last treatment, elderly mice were inoculated with T. cruzi. Young animals were infected at 8-weeks-old. Untreated elderly mice exhibited increase parasitemia, parasite load and myocarditis, which were associated to down-regulation in IL-2, IL-6, IFN-γ, TNF, anti-T. cruzi immunoglobulin G (IgG) total, IgG1 and IgG2a plasma levels, inducible nitric oxide synthase (iNOS) gene expression and nitric oxide (NO) cardiac production, as well as upregulation in Arginase-1 gene expression and arginase activity compared to young animals. These parameters were improved in rapamycin-pretreated elderly mice, which exhibited a better parasitological control, reduced heart inflammation and microstructural damage. These responses were associated with a better balance between Th1 and Th2 effectors similar to that observed in young animals, including an improved activation of Th1 cytokines and the iNOS pathway that positively regulates NO biosynthesis, contradicting the predominant activation of the arginase pathway in untreated elderly animals. Thus, our findings suggest that chronic pretreatment with rapamycin can attenuate immunosenescence in mice, contributing to prolong parasite resistance and attenuate acute myocarditis in elderly host challenged by T. cruzi., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Using plant-based extracts and their constituents has been suggested as an alternative tool to replace or integrate with the synthetic compounds used to manage insect pests. Here, we evaluated the potential of extracts obtained from Ficus carica Linn (Moraceae) branches and leaves against the Neotropical brown stink bug, Euschistus heros, one of the most prevalent insect pests in soybean fields. We further isolated and evaluated the toxicity of the extracts' major components against E. heros. Additionally, by using computational docking analysis and toxicological approaches, we assessed the physiological basis for the selectivity of these extracts against beneficial insects such as pollinator bees (i.e. Apis mellifera and the Neotropical stingless bee Partamona helleri), ladybeetles (Eriopis connexa and Coleomegilla maculata), and lacewings (Chrysoperla externa)., Results: Our results demonstrate that branch (LC 50  = 5.9 [4.7-7.1] mg mL -1 ) and leaf (LC 50  = 14.1 [12.5-15.4] mg mL -1 ) extracts exhibited similar toxicity against E. heros. Our phytochemical analysis revealed psoralen and bergapten furanocoumarins as the major components of the extract. Based on our computational predictions, these molecules' differential abilities to physically interact with the acetylcholinesterases of E. heros and beneficial insects play relevant roles in their selectivity actions. The estimated LC 90 values of branch (30.0 mg mL -1 ) and leaf (30.0 mg mL -1 ) extracts killed less than 12% of the beneficial insects., Conclusion: Overall, our findings revealed that furanocoumarin-rich extracts obtained from F. carica extracts have the potential to be used as alternative tools in the integrated management of stink bug pests. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

Deltamethrin (DTM) is a pyrethroid insecticide widely used for agricultural purposes. Exposure to DTM has proven to be harmful to humans, but whether low, environmental concentrations of this pesticide also poses a threat to wild mammals is still unknown. In Neotropical areas, bats play important roles in contributing to forest regeneration. We investigated the effects of DTM exposure on the reproductive function of male Neotropical fruit-eating bats (Artibeus lituratus), known for contributing to reforestation through seed dispersal in Neotropical Forests. Bats were assigned to 3 groups: control (fed with papaya); DTM2 (fed with papaya treated with DTM at 0.02 mg/kg) and DTM4 (fed with papaya treated with DTM at 0.04 mg/kg) for seven days. Bats from DTM2 and DTM4 groups showed increased testicular levels of nitric oxide and superoxide dismutase and catalase activities. The germinal epithelium from DTM4 bats showed non-viable cells and cell desquamation, indicating microscopic lesions and Leydig cells atrophy. Our results demonstrate the onset of cell degeneration that may affect the reproductive function in DTM exposed bats., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Ethnopharmacological Relevance: Green tea, traditionally used as antidiabetic medicine, positively affects the diabetic nephropathy. It was assumed that these beneficial effects were due to the hypoglycemiant capacity of the tea, wich reduces the glycemic overload and, consequently, the advanced glycation end products rate and oxidative damage. However, these results are still controversial, since tea is not always able to exert a hypoglycemic action, as demonstrated by previous studies., Aim: Investigate if green tea infusion can generate positive outcomes for the kidney independently of glycemic control, using a model of severe type 1 diabetes., Material and Methods: We treated streptozotocin type 1 diabetic young rats with 100 mg/kg of green tea, daily, for 42 days, and evaluated the serum and tissue markers for stress and function. We also analyzed the ion dynamics in the organ and the morphological alterations promoted by diabetes and green tea treatment. Besides, we analyzed, by an in silico approach, the interactions of the green tea main catechins with the proteins expressed in the kidney., Results: Our findings reveal that the components of green tea can interact with the proteins participating in cell signaling pathways that regulate energy metabolism, including glucose and glycogen synthesis, glucose reabsorption, hypoxia management, and cell death by apoptosis. Such interaction reduces glycogen accumulation in the organ, and protects the DNA. These results also reflect in a preserved glomerulus morphology, with improvement in pathological features, and suggesting a prevention of kidney function impairment., Conclusion: Our results show that such benefits are achieved regardless of the blood glucose status, and are not dependent on the reduction of hyperglycemia., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Diabetes is a highly prevalent health condition affecting many people worldwide. In vitro studies have described the positive effects of cloves and its major compound, eugenol, in the treatment of diabetes. However, it is unclear whether the effects of this compound are negative, neutral, or positive, on hyperglycemic animals. Therefore, a meta-analytical review was conducted to determine the magnitude of effects of eugenol on variables directly and indirectly related to diabetes. This study revealed that eugenol treatment decreased the glucose levels and the activity of carbohydrate-metabolizing enzymes, ameliorated the lipid profile, and reduced the oxidative, renal, and hepatic damages in hyperglycemic rodents. Moreover, eugenol alleviated the weight loss and restored the activity of the antioxidant defense system. Insulin levels was not affected by eugenol treatment. Also, mixed model analyses revealed that the use of purified or non-purified eugenol and the concentrations administered significantly affected the treatment outcome. In conclusion, our findings indicate that eugenol may have potential therapeutic effects in the treatment of diabetes. Furthermore, this study can direct future preclinical and clinical trials, with important implications for human health., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Fishes can change their physiological responses when threatened by the presence of predators. Such physiological plasticity, however, usually implies costs that may impede organismal development and reproduction and reduce the ability to cope with other biotic and abiotic stresses. Here, we evaluated the growth and stress biomarker responses in sexually reversed Nile tilapia, Oreochromis niloticus, fingerlings indirectly threatened by the presence of the aquatic insect predator Belostoma anurum (Hemiptera: Belostomatidae). We also evaluated whether the presence of B. anurum would affect growth in fingerlings that received food containing the masculinizing hormone 17 α-methyltestosterone. The antioxidant responses were evaluated by measuring the activity of enzymes (e.g., superoxide dismutase, catalase, and glutathione-S-transferase). Oxidative stress biomarkers (e.g., malondialdehyde and nitric oxide) and blood glucose and lactate responses were also evaluated. Our results revealed that predator exposure did not affect growth in O. niloticus fingerlings reared in the presence or absence of the masculinizing hormone. However, sexually reversed tilapia fingerlings significantly increased not only the glucose and lactate blood levels, but also exhibited increased activities of superoxide dismutase and glutathione-S-transferases enzymes when threatened by the presence of B. anurum nymphs. Collectively, our findings indicate that despite not exhibiting reduced growth performance, sexually reversed tilapia fingerlings were physiologically stressed by the presence of the predator, which may reduce their ability to face environmental and abiotic stresses., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Properties attributed to the Panax ginseng are also attributed to the Brazilian ginseng, such as adaptogenic and aphrodisiac effects. There are studies demonstrating that the Brazilian ginseng (BGE) possibly increases the serum levels of testosterone and nitric oxide in mice and rats. The present study aimed to evaluate the effects of its extract on male fertility and sperm quality. Male Swiss mice (n = 60) were divided into six groups. The control animals were provided 0.5 mL of water, and 0.5 mL of water containing 7 mg/kg per day (d) sildenafil citrate. Other animals were treated with BGE at 100 mg/kg/d, 200 mg/kg/d, and 400 mg/kg/d by gavage for 42 days. Finally, animals from the last group received 200 mg/kg BGE every 3 days (3-3d) by gavage for 42 days. The results showed a reduction in the number of resistant spermatids in the testis and damage to daily sperm production, culminating in a reduction in the number of epididymal spermatozoa. Although the sperm quality decreased in all experimental animals, only males treated with BGE 100 mg/kg/d showed pre and post implantation embryo losses. We concluded that BGE alters sperm viability compromising the embryonic development after implantation.

Conventional treatments for metastatic melanomas are still ineffective and generate numerous side effects, justifying the search for new therapies. The antimetastatic effect of the named N-(2-(4-bromophenylamino)-5-(trifluoromethyl)phenyl)nicotinamide (SRVIC30) compound has been previously demonstrated in murine melanoma. Herein, we aimed to evaluate its effect when topically administrated in a murine subcutaneous melanoma model. For that, mice C57BL/6 were injected subcutaneously with 2 × 10 B16-F10 cells. Topical treatment began when tumors became visible on animal's back. Therefore, tumor volume was measured three times a week until it reaches 12 mm approximately. At this point, 40 mg oil-in-water cream (Lanette) without (control mice; n = 10) or with SRVIC30 compound (SRVIC30 group; n = 10 animals) were spread daily over the tumor external surface using a small brush for 14 days. The treatments increased the percentage of peroxidase antioxidant enzyme and dead cells via caspase-3 activation, with a consequent deposit of collagen fibers in the tumors. In addition, the skin of treated animals showed the presence of inflammatory infiltrate. Finally, SRVIC30 did not show signs of toxicity. Thus, we concluded that the topic administration of SRVIC30 was able to influence crucial anticancer processes such as tumor cells apoptosis and surrounding microenvironment.

Plant biodiversity is a source of potential natural products for the treatment of many diseases. One of the ways of discovering new drugs is through the cytotoxic screening of extract libraries. The present study evaluated 196 extracts prepared by maceration of Brazilian Atlantic Forest trees with organic solvents and distilled water for cytotoxic and antimetastatic activity. The MTT assay was used to screen the extract activity in MCF-7, HepG2 and B16F10 cancer cells. The highest cytotoxic extract had antimetastatic activity, as determined in in vitro assays and melanoma murine model. The organic extract of the leaves of Athenaea velutina (EAv) significantly inhibited migration, adhesion, invasion and cell colony formation in B16F10 cells. The phenolic compounds and flavonoids in EAv were identified for the first time, using flow injection with electrospray negative ionization-ion trap tandem mass spectrometry analysis (FIA-ESI-IT-MS n ). EAv markedly suppressed the development of pulmonary melanomas following the intravenous injection of melanoma cells to C57BL/6 mice. Stereological analysis of the spleen cross-sections showed enlargement of the red pulp area after EAv treatment, which indicated the activation of the haematopoietic system. The treatment of melanoma-bearing mice with EAv did not result in liver damage. In conclusion, these findings suggest that A velutina is a source of natural products with potent antimetastatic activity., (© 2020 Company of the International Journal of Experimental Pathology (CIJEP).)

It is herein described the preparation and evaluation of antimetastatic activity of twenty-six cinnamic acid derivatives containing 1,2,3-triazolic portions. The compounds were prepared using as the key step the Copper(I)-catalyzed azide (A)-alkyne (A) cycloaddition (C) (CuAAC reaction), also known as click reaction, between alkynylated cinnamic acid derivatives and different benzyl azides. The reactions were carried in CH 2 Cl 2 /H 2 O (1:1 v/v) at room temperature, and the triazole derivatives were obtained in yields ranging from 73%99%. Reaction times varied from 5 to 40 min. The identity of the synthesized compounds was confirmed by IR and NMR ( 1 H and 13 C) spectroscopic techniques. They were then submitted to in vitro bioassays to investigate how they act over metastatic behavior of murine melanoma. The most potent compound, namely 3-(1-benzyl-1H-1,2,3-triazol-4-yl)propyl cinnamate (9a), showed significant antimetastatic and antiproliferative activities against B16-F10 cells. In addition, gelatin zymography and molecular docking analyses pointed to the fact that this compound has potential to interact with matrix metalloproteinase 9 (MMP-9) and MMP-2, which are directly involved in melanoma progression. Therefore, these findings suggest that cinnamic acid derivatives containing 1,2,3-triazolic portions may have potential for development of novel candidates for controlling malignant metastatic melanoma., (Copyright © 2018. Published by Elsevier Ltd.)

The Serine/arginine-rich protein kinases (SRPK) are involved in pre-mRNA splicing control through the phosphorylation of the SR protein family of splicing factors. Over the last years, several studies have shown the relevance of SRPK for human cancers and their potential as promising drug targets. In this context, we have previously selected three trifluoromethyl arylamides (named here as SRVIC24, SRVIC30 and SRVIC36) with improved in vitro antileukemia effect and ability of impairing the cellular activity of SRPK. Given the increasing amount of reports on the implication of these kinases in metastatic cancers, in this study, we have evaluated the antimetastatic effect of these compounds and the known SRPK inhibitor (SRPIN340) on a murine model of metastatic melanoma. The compounds were able to impact the melanoma cell metastatic behavior by decreasing migration, invasion, adhesion, and colony formation in in vitro assays. Also, they presented antimetastatic in vivo activity, without apparent signs of systemic toxicity after treatments, as revealed by the histology of organs and analysis of key serum biochemical markers. Moreover, the effect of the treatments on SRPK1 nuclear translocation and SR protein phosphorylation was observed. Finally, molecular docking studies were carried out to gain structural information on the SRPK-compound complexes. Together, these data suggest that SRPK pharmacological inhibition should be considered as an interesting therapeutic strategy against metastatic cancers., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Arsenic impairs male reproductive functions. However, it is not clear whether different arsenic compounds similarly affect fertility. In this study, we compared the impact of sodium arsenite and arsenate on sperm quality and fertility. After 56 d exposure, male Wistar rats were mated and pregnant females were evaluated by fertility indexes. Clearly, exposure to 10 mg/L arsenite reduced daily sperm production via H 2 O 2 overproduction and germ cells loss. Animals from this group also showed a decrease in epididymal sperm counts and percentage of sperm with intact membranes. Moreover, they presented low fertility potential and high preimplantation loss. In contrast, 10 mg/L arsenate caused oxidative stress in testis, mineral imbalance in epididymis, and sperm membranes damage, with no effects on fertility. Both arsenic compounds at 0.01 mg/L altered reproductive parameters. We concluded that arsenite is more harmful than arsenate to sperm quality and male fertility, with negative influences in early pregnancy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aluminum (Al) is the most widely distributed metal in the environment and is extensively used in human daily life without any known biological function. It is known that exposure to high concentrations of Al impacts negatively on serum testosterone levels, testicular histomorphometry, and sperm parameters; however, no information is available about the effects of low exposure levels on reproduction. International organizations have established the Al concentration tolerated in drinking water as 3.35 × 10 -4  mg/kg. Therefore, we aimed to compare the effects of long-term exposure to low and high concentrations of Al on male reproductive functions, focusing on testis, epididymis, and sperm parameters. Adult Wistar rats were exposed to aluminum chloride (AlCl 3 ) at 6.7 × 10 -5 , 3.35 × 10 -4 , 10, and 40 mg/kg for 112 days by gavage. Al-exposed animals presented low values of testis and epididymis weight, and serum testosterone levels when compared to controls. The stereology of Leydig cells, epididymis histomorphometry, sperm motility, and structural integrity of sperm membranes changed depending on the Al concentration. In regard to epididymis histomorphometry, the initial segment and caput regions were more affected by Al exposure than distal regions. Otherwise, the histology of testis and epididymis did not alter after the Al exposure, as well as sperm morphology. In summary, we concluded that the consequences of Al exposure at low levels were as negative as high levels on reproductive parameters, suggesting adverse impact on male fertility.

Objective: A systematic review was conducted to analyze Brazilian scientific and technological production related to the dental materials field over the past 50 years., Material and Methods: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (Prisma) statement. Searches were performed until December 2014 in six databases: MedLine (PubMed), Scopus, LILACS, IBECS, BBO, and the Cochrane Library. Additionally, the Brazilian patent database (INPI - Instituto Nacional de Propriedade Industrial) was screened in order to get an overview of Brazilian technological development in the dental materials field. Two reviewers independently analyzed the documents. Only studies and patents related to dental materials were included in this review. Data regarding the material category, dental specialty, number of documents and patents, filiation countries, and the number of citations were tabulated and analyzed in Microsoft Office Excel (Microsoft Corporation, Redmond, Washington, United States)., Results: A total of 115,806 studies and 53 patents were related to dental materials and were included in this review. Brazil had 8% affiliation in studies related to dental materials, and the majority of the papers published were related to dental implants (1,137 papers), synthetic resins (681 papers), dental cements (440 papers), dental alloys (392 papers) and dental adhesives (361 papers). The Brazilian technological development with patented dental materials was smaller than the scientific production. The most patented type of material was dental alloys (11 patents), followed by dental implants (8 patents) and composite resins (7 patents)., Conclusions: Dental materials science has had a substantial number of records, demonstrating an important presence in scientific and technological development of dentistry. In addition, it is important to approximate the relationship between academia and industry to expand the technological development in countries such as Brazil.

The ethyl-4-dimethylaminobenzoate (EDAB) is widely used as a coinitiator of the camphorquinone (CQ), but in acidic circumstances it might present some instability, reducing the polymerization efficiency of the material. Considering this, new coinitiators are being evaluated. Hence, this study evaluated the kinetic of polymerization (KP), the degree of conversion (DC), and the rate of polymerization (RP ) of experimental resin adhesives containing 1,3-diethyl-2-thiobarbituric acid (TBA) as a coinitiator of the CQ. The experimental monomeric blend was prepared with bisphenol A glycidyl dimethacrylate, 2-hydroxyethyl methacrylate, and acidic monomers. CQ was added at 1 mol % as photoinitiator. Six groups were formulated: four containing concentrations of 0.1, 0.5, 1, and 2 mol % of TBA, one without coinitiator, and the last one containing 1 mol % of EDAB (control group). The KP and the RP were performed using real-time Fourier Transform infrared spectroscopy. The group without coinitiator has not formed a polymer, whereas the addition of TBA resulted in the conversion of monomers in polymer. The DC of the adhesives was as higher as the increase in the TBA content. The group with 2 mol % of TBA presented improved DC and reactivity (RP ) than the other groups and the control one. Hence, the TBA has performed as a coinitiator of the CQ for the radical polymerization of methacrylate resin adhesives and it has improved the DC and the reactivity of the materials. Thus, it is a potential coinitiator for the photopolymerization of dental materials., (Copyright © 2013 Wiley Periodicals, Inc., a Wiley Company.)

Objectives: The purpose of this study was to evaluate the reactivity and polymerization kinetics behavior of a model dental adhesive resin with water-soluble initiator systems., Methods: A monomer blend based on Bis-GMA, TEGDMA and HEMA was used as a model dental adhesive resin, which was polymerized using a thioxanthone type (QTX) as a photoinitiator. Binary and ternary photoinitiator systems were formulated using 1mol% of each initiator. The co-initiators used in this study were ethyl 4-dimethylaminobenzoate (EDAB), diphenyliodonium hexafluorophosphate (DPIHFP), 1,3-diethyl-2-thiobarbituric acid (BARB), p-toluenesulfinic acid and sodium salt hydrate (SULF). Absorption spectra of the initiators were measured using a UV-Vis spectrophotometer, and the photon absorption energy (PAE) was calculated. The binary system camphorquinone (CQ)/amine was used as a reference group (control). Twelve groups were tested in triplicate. Fourier-transform infrared spectroscopy (FTIR) was used to investigate the polymerization reaction during the photoactivation period to obtain the degree of conversion (DC) and maximum polymerization rate (R(p)(max)) profile of the model resin., Results: In the analyzed absorption profiles, the absorption spectrum of QTX is almost entirely localized in the UV region, whereas that of CQ is in the visible range. With respect to binary systems, CQ+EDAB exhibited higher DC and R(p)(max) values. In formulations that contained ternary initiator systems, the group CQ+QTX+EDAB was the only one of the investigated experimental groups that exhibited an R(p)(max) value greater than that of CQ+EDAB. The groups QTX+EDAB+DPIHFP and QTX+DPIHFP+SULF exhibited values similar to those of CQ+EDAB with respect to the final DC; however, they also exhibited lower reactivity., Significance: Water-soluble initiator systems should be considered as alternatives to the widely used CQ/amine system in dentin adhesive formulations., (Copyright © 2012 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.)

Objective: Actinic cheilitis (AC) is a precancerous lesion of the lip vermillion caused by prolonged exposure to ultraviolet light. The aim of this study was to evaluate the effect of 3% diclofenac in 2.5% hyaluronic acid gel in the treatment of AC., Methods: Thirty-four patients with chronic AC were treated twice a day with topical diclofenac during a period of 30 to 180 days. The individuals were followed up every 15 days by means of clinical examination and digital photographic documentation., Results: Of the 27 patients that completed the study, 12 (44%) showed complete remission of the whitish plaques and exfoliative areas, and 15 (56%) had partial remission of the clinical picture of cheilitis. The latter group was submitted to excision of the leukoplakic areas which diagnosis varied from mild to moderate epithelial dysplasia., Conclusions: The results suggest a promising role for diclofenac in hyaluronic acid gel in the treatment of AC. This treatment has the advantages of not being invasive and showing few side effects.

Despite the large number of published cases about oral and maxillofacial pediatric lesions, the literature is scarce on epidemiological studies regarding the prevalence of these entities. This study retrieved oral and maxillofacial pediatric lesions from the Center of Diagnosis of Oral Diseases (CDDB) at the Dental School of the Federal University of Pelotas (UFPEL), comprising a 20-year period (1983-2002). From the total of 9,465 biopsies received in this period, 625 (6.6%) were from children aged 0 to 14 years. Regardless of the histopathological diagnosis, patient data referring to lesion location, sex and age were collected. Diagnoses were grouped in 13 categories. As much as 89% of the cases occurred in patients aged 7 to 14 years (53% in females and 47% in males). Mucocele (17.2%) was the most common type of lesion, followed by dentigerous cyst (8.6%). In the category of odontogenic tumors, odontoma was the most frequent lesion (64.2%). Malignant lesions were observed in a small section of the sample (1.2%). Generally, the results of the present study are in line with those reported in the literature concerning the most prevalent lesions in the pediatric population. Most lesions were benign, and malignant lesions were diagnosed in a very small part of the sample.

Purpose: To investigate the influence of different water concentrations in the solvents of self-etching primers on microtensile bond strength (LTBS) of an experimental adhesive system., Materials and Methods: Five experimental self-etching primers with 0, 5, 10, 20 and 40 (wt%) water as solvent were formulated. An experimental adhesive resin (AD-50) was also synthesized to create one experimental self-etching adhesive system. Clearfil SE Bond (CSEB) was used as the commercial reference. Sixty bovine incisors were randomly separated into 6 groups. Buccal enamel was removed to expose the superficial coronal dentin; this surface was polished wet to create a standardized smear layer. After rinsing, water was removed, leaving the surface visibly dried. The dentin surfaces were etched with primer and air dried, adhesive resin was applied and photoactivated, then the composite resin restoration was placed. After storage for 24 h, the specimens were sectioned with a cooled diamond saw at low speed. Microtensile bond strength was measured and data were analyzed with one-way ANOVA/Tukey's test (alpha = 0.05)., Results: ANOVA showed that primer composition was a significant factor for bond strength. There was no significant difference in bond strengths between the primers with a water concentration of 40% (53.9 +/- 12.7 MPa), 20% (51.1 +/- 11.5 MPa, and 10% (47.5 +/- 11.4 MPa), and CSEB (50.7 +/- 9.8 MPa). The groups with 5% (38.6 +/- 12.9 MPa) and 0% (31.5 +/- 7.5 MPa) water presented similar bond strengths amongst themselves but were statistically significantly lower than that of the other groups., Conclusion: The water concentration in the primer solvent exercises a significant influence on the bond strength of this experimental self-etching adhesive system.

Objectives: The aim of this study was to synthesize an acidic monomer using an alternative synthetic pathway and to evaluate the influence of the acidic monomer concentration on the microtensile bond strength to dentin., Methods: The intermediary 5-hydroxypentyl methacrylate (HPMA) was synthesized through methacrylic acid esterification with 1,5-pentanediol, catalyzed by p-toluenesulfonic acid. To displace the reaction balance, the water generated by esterification was removed by three different methods: anhydrous sodium sulfate; molecular sieves or azeotropic distillation. In the next step, a phosphorus pentoxide (4.82 mmol) slurry was formed in cold acetone and 29 mmol of HPMA was slowly added by funnel addition. After the reaction ended, solvent was evaporated and the product was characterized by 1HNMR and FTIR. The phosphate monomer was introduced in a self-etch primer at concentrations of 0, 15, 30, 50, 70 and 100 wt%. Clearfil SE Bond was used as commercial reference. Microtensile bond strength to dentin was evaluated 24h after the bonding procedures, followed by fracture analysis (n=20). Data was submitted to ANOVA and Tukey's post hoc test., Results: The highest yield was obtained (62%) when azeotropic distillation was used, while the reaction with molecular sieves was not feasible. The phosphoric moiety attachment to the monomer was successfully performed with a quantitative yield that reached around 100%. The acidic monomer concentration significantly affected the bond strength and the highest mean (55.1+/-12.8 MPa) was obtained when 50% of acidic monomer was used., Conclusion: The synthesis pathways described in the present study appear to be a viable alternative for developing phosphate monomers.