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Melanoma is the most aggressive form of skin cancer and arises from melanocyte gene mutation. This disease is multifactorial, but its main cause is the excessive exposure to ultraviolet radiation. Currently, available chemotherapy has shown little expressive results, which may justify the high use of natural products to treat this cancer. We performed a systematic review to compile the results of studies carried out in murine models and investigated the effect of plant extracts on melanoma treatment. Papers were selected in MEDLINE/Pubmed and Scopus according to the PRISM statement. Search filters were developed using three parameters: plant extract, melanoma, and animal model. The 35 identified studies were all submitted to the criteria described in the ARRIVE guidelines. The different extracts showed antiangiogenic, antimetastatic, antioxidant, and anti-inflammatory activity, and also proved to be effective in cell cycle modulation and apoptosis evasion. Bias analysis evidenced the absence of standardized experimental designs, as well as failures in statistical tests and in the presentation of results. The analysis of the studies suggests that the use of plant extracts is effective for the treatment of melanoma in murine models.
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Melanoma/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , CamundongosRESUMO
STATEMENT OF PROBLEM: Clinical data regarding newly introduced laser-sintered removable partial dentures (RPDs) are needed before this technique can be recommended. Currently, only a few clinical reports have been published, with no clinical studies. PURPOSE: This clinical trial compared short-term satisfaction in patients wearing RPDs fabricated with conventional or computer-aided design and computer-aided manufacturing (CAD-CAM) laser-sintering technology. MATERIAL AND METHODS: Twelve participants with partial edentulism were enrolled in this pilot crossover double-blinded clinical trial. Participants were randomly assigned to wear cast or CAD-CAM laser-sintered RPDs for alternate periods of 30 days. The outcome of interest was patient satisfaction as measured using the McGill Denture Satisfaction Instrument. Assessments was conducted at 1, 2, and 4 weeks. The participant's preference in regard to the type of prosthesis was assessed at the final evaluation. The linear mixed effects regression models for repeated measures were used to analyze the data, using the intention-to-treat principle. To assess the robustness of potential, incomplete adherence, sensitivity analyses were conducted. RESULTS: Statistically significant differences were found in patients' satisfaction between the 2 methods of RPD fabrication. Participants were significantly more satisfied with laser-sintered prostheses than cast prostheses in regard to general satisfaction, ability to speak, ability to clean, comfort, ability to masticate, masticatory efficiency, and oral condition (P<.05). At the end of the study, 5 participants preferred the laser-sintered, 1 preferred the cast RPD, and 3 had no preference. CONCLUSIONS: The use of CAD-CAM laser-sintering technology in the fabrication of removable partial dentures may lead to better outcomes in terms of patient satisfaction in the short term. The conclusion from this pilot study requires confirmation by a larger randomized controlled trial. CLINICAL TRIAL: ClinicalTrials.gov. A study about patient satisfaction with laser-sintered removable partial dentures; NCT02769715.
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Desenho Assistido por Computador , Planejamento de Dentadura/métodos , Prótese Parcial Removível , Lasers , Satisfação do Paciente , Idoso , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos PilotoRESUMO
INTRODUCTION: In addition to their cholesterol-lowering effects, the statin class of drugs appears to enhance osteogenesis and suppress bone resorption, which could be a clinical concern during orthodontic treatment. In this animal study, we aimed to determine whether atorvastatin (ATV) affects orthodontic tooth movement (OTM) through osteoclast inhibition. Furthermore, we analyzed the potential adverse effects of ATV on long-bone turnover and endochondral ossification. METHODS: Rats were administered ATV (15 mg/kg) or saline solution via gavage (n = 12 animals/group), starting 2 weeks before initial OTM. Tooth displacement was measured after 7, 14, and 21 days. Histologic sections of the maxilla and femur were obtained after 14 and 21 days of OTM and stained (hematoxylin and eosin; TRAP assay) for histomorphometric analysis. RESULTS: ATV was associated with significant (P <0.05) reductions in OTM and osteoclast counts. Independently of drug administration, OTM increased the number of osteoclasts and reduced the bone-volume ratio compared with the control maxillae without OTM. Long-term statin administration did not appear to affect femoral endochondral ossification. CONCLUSIONS: This experimental study showed that the long-term use of ATV can significantly promote osteoclast inhibition and slow the OTM in the first week in rats. Under physiologic conditions, the drug did not affect bone turnover and endochondral ossification.
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Atorvastatina/farmacologia , Osteogênese/efeitos dos fármacos , Técnicas de Movimentação Dentária , Animais , Atorvastatina/efeitos adversos , Remodelação Óssea/efeitos dos fármacos , Masculino , Ratos , Ratos WistarRESUMO
OBJECTIVE: To characterize the profile of microbial communities colonizing titanium implants with different surface treatments after exposure to the oral environment at the genus or higher taxonomic level. MATERIAL AND METHODS: Sixteen titanium disks, machined or sandblasted large-grit and acid-etched (SLA), were mounted on removable intraoral splints worn by four patients. After 24 h of intraoral exposure, biofilm samples were collected from disks and supra/subgingival teeth areas. The 16S rDNA genes from each sample were amplified, sequenced with the Miseq Illumina instrument and analyzed. RESULTS: A total of 29 genera and seven more inclusive taxa, representing the phyla Firmicutes, Proteobacteria, Fusobacteria, Bacteroidetes, Actinobacteria and candidate division TM7 were identified in both titanium surfaces and teeth. No differences were found in relation to the operational taxonomic units (OTUs) and microbial diversity, assessed by Chao 1 and Shannon indices, when comparing SLA and machined titanium surfaces. CONCLUSIONS: Machined and SLA surfaces are colonized by similar numbers of prokaryotic OTUs after 24 h of exposure to the oral environment. Higher complexity of the titanium surface topography in the initial phase of biofilm maturation does not seem to significantly influence the colonizing microbiota.
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Bactérias/genética , Biofilmes , Implantes Dentários/microbiologia , Titânio , Adulto , Bactérias/classificação , Bactérias/isolamento & purificação , DNA Ribossômico , Humanos , Microbiota , Filogenia , Análise de Sequência de DNA/métodos , Propriedades de SuperfícieRESUMO
Tumours display different cell populations with distinct metabolic phenotypes. Thus, subpopulations can adjust to different environments, particularly with regard to oxygen and nutrient availability. Our results indicate that progression to metastasis requires mitochondrial function. Our research, centered on cell lines that display increasing degrees of malignancy, focused on metabolic events, especially those involving mitochondria, which could reveal which stages are mechanistically associated with metastasis. Melanocytes were subjected to several cycles of adhesion impairment, producing stable cell lines exhibiting phenotypes representing a progression from non-tumorigenic to metastatic cells. Metastatic cells (4C11+) released the highest amounts of lactate, part of which was derived from glutamine catabolism. The 4C11+ cells also displayed an increased oxidative metabolism, accompanied by enhanced rates of oxygen consumption coupled to ATP synthesis. Enhanced mitochondrial function could not be explained by an increase in mitochondrial content or mitochondrial biogenesis. Furthermore, 4C11+ cells had a higher ATP content, and increased succinate oxidation (complex II activity) and fatty acid oxidation. In addition, 4C11+ cells exhibited a 2-fold increase in mitochondrial membrane potential (ΔΨmit). Consistently, functional assays showed that the migration of cells depended on glutaminase activity. Metabolomic analysis revealed that 4C11+ cells could be grouped as a subpopulation with a profile that was quite distinct from the other cells investigated in the present study. The results presented here have centred on how the multiple metabolic inputs of tumour cells may converge to compose the so-called metastatic phenotype.
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Glutamina/metabolismo , Melanócitos/fisiologia , Melanoma/metabolismo , Fosforilação Oxidativa , Consumo de Oxigênio/fisiologia , Animais , Linhagem Celular Tumoral , Movimento Celular , Glucose/metabolismo , Glutaminase/metabolismo , Glutamina/genética , Lactatos/metabolismo , Melanócitos/patologia , Melanoma/patologia , Potenciais da Membrana/fisiologia , Metabolismo , Camundongos , Oxirredução , FenótipoRESUMO
Although the order Rodentia does not present a high risk of extinction compared to mammals as a whole, several families demonstrate high levels of threat and/or data deficiency, therefore highlighting the need for targeted research and the application of ecological and reproductive data to the development of conservation actions. The order Rodentia, the largest among mammals, includes 9 families, and the family Cricetidae is the most diverse of the Brazilian rodents. In Brazil, 12 of the 16 genera of Oecomys are found. Oecomys bicolor is known in Brazil as the 'arboreal rat' and is, found in dry, deciduous and tropical forests. The mean body weight of Oecomys bicolor was 35.8 g and the gonadal, tubular and epithelial somatic indexes were, 0.53%, 0.47% and 0.37%, respectively. Seminiferous tubules volume density was 89.72% and the mitotic and meiotic indexes corresponded to 8.59 and 2.45 cells, respectively, and the yield of spermatogenesis was 23.83 cells. The intertubular compartment represented 10.28% of the testis parenchyma and around 5% of the interstitial space was occupied by Leydig cells, whose number per gram of testis was 11.10 × 107 cells. By evaluating the biometric and histomorphometric characteristics of the testis, there is evidence that this species has a high investment in reproduction. Due to the high contribution of the seminiferous epithelium and the intertubular compartment in this species, compared to the others of the same family, it is possible to infer that the species Oecomys bicolor has a promiscuous reproductive behaviour.
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Arvicolinae , Células Intersticiais do Testículo , Espermatogênese , Testículo , Animais , Espermatogênese/fisiologia , Masculino , Testículo/anatomia & histologia , Testículo/fisiologia , Células Intersticiais do Testículo/citologia , Células Intersticiais do Testículo/fisiologia , Arvicolinae/anatomia & histologia , Arvicolinae/fisiologia , Túbulos Seminíferos/anatomia & histologia , BrasilRESUMO
Thimet oligopeptidase (THOP) is a cytosolic metallopeptidase known to regulate the fate of post-proteasomal peptides, protein turnover and peptide selection in the antigen presentation machinery (APM) system. Oxidative stress influences THOP expression and regulates its proteolytic activity, generating variable cytosolic peptide levels, possibly affecting the immune evasion of tumor cells. In the present work, we examined the association between THOP expression/activity and stress oxidative resistance in human leukemia cells using the K562 cell line, a chronic myeloid leukemia (CML), and the multidrug-resistant (MDR) Lucena 1 (K562-derived MDR cell line) as model. The Lucena 1 phenotype was validated under vincristine treatment and the relative THOP1 mRNA levels and protein expression compared to K562 cell line. Our data demonstrated increased THOP1 gene and protein levels in K562 cells in contrast to the oxidative-resistant Lucena 1, even after H2O2 treatment, suggesting an oxidative stress dependence in THOP regulation. Further, it was observed higher basal levels of reactive oxygen species (ROS) in K562 compared to Lucena 1 cell line using DHE fluorescent probe. Since THOP activity is dependent on its oligomeric state, we also compared its proteolytic activity under reducing agent treatment, which demonstrated that its function modulation with respect to changes in redox state. Finally, the mRNA expression and FACS analyses demonstrated a reduced expression of MHC I only in K562 cell line. In conclusion, our results highlight THOP redox modulation, which could influence antigen presentation in multidrug resistant leukemia cells.
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Peróxido de Hidrogênio , Leucemia , Humanos , Peróxido de Hidrogênio/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Células K562 , Leucemia/tratamento farmacológico , Leucemia/genética , Estresse Oxidativo , Peptídeos , RNA MensageiroRESUMO
This review aims to establish an association between traditional and scientific knowledge to allow the evaluation of the effectiveness of medicinal plants, as well as their risks based on the testicular microenvironment. A systematic search was performed using PRISMA guidelines. The descriptors were structured based on search filters built for three domains: Animals, Plants, and Testis. The filters on the PubMed/Medline platform were constructed using a hierarchical distribution of the MeSH Terms. Methodological quality assessments were performed using the SYRCLE risk bias tool. Data on testicular cells, hormones and biochemistry, sperm, and sexual behavior were evaluated and compared. The search came out with 2644 articles, and 36 articles met the inclusion criteria and were used in this review. The included studies analyzed testicular cells from murine models treated with crude plant extracts. Plant extracts act directly on the hypothalamic-pituitary axis and/or directly on testicular cells, inhibiting and stimulating the reproductive process, thus causing alterations in fertility rates. Apiaceae and the Cucurbitaceae families are the most used in male reproductive biology experiments, being Apiaceae described as sexual stimulants, while Cucurbitaceae are the main sources of deleterious effects on the male reproductive system.
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Sementes , Testículo , Masculino , Camundongos , Animais , Estrutura Molecular , Espermatozoides , Extratos Vegetais/farmacologiaRESUMO
It is known that cadmium induces damage to the testis. However, the significant cadmium impact on the testicular architecture and the mechanisms involved in this process are not clear. Besides, the relationship between dose, route, and time of exposure and injuries remains poorly understood. Thus, we aimed to assess whether cadmium exposure in any dose, route, and time of exposure causes significant alteration in the testicular tissue of murine models, as well as the main mechanisms involved. We performed a structured search on the Medline/PubMed and Scopus databases to retrieve studies published until September 2018. The results were organized into an Adverse Outcome Pathway (AOP) framework. Also, a bias analysis of included studies was performed. We included 37 studies, and most of them identified significant histopathologies in both tubule and intertubule regarding routes, in a dose- and time-dependent manner. The damages were observed after the first hours of exposure, mainly vascular damages suggesting that vasculature failure is the primary mechanism. The AOP showed that potential molecular initiating events may mimic and interfere with essential elements disrupting proteins (structural and antioxidants), change in the oxidative phosphorylation enzyme activities, and gene expression alteration, which lead to reproductive failure (adverse outcome). Analysis of methodological quality showed that the current evidence is at high risk of bias. Despite the high risk of bias, cadmium triggers significant lesions in the testis of murine models, regarding routes, in a dose- and time-dependent manner, mainly due to vascular changes. Therefore, cadmium is a risk factor for male reproductive health.
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Cádmio , Testículo , Animais , Antioxidantes , Cádmio/toxicidade , Modelos Animais de Doenças , Masculino , CamundongosRESUMO
The anatomy of the dura mater's venous sinuses is important in the veterinary clinical and surgical area, for cranial procedures and interventions of wild animals, in addition to assisting in the management of neurological diseases, which can prevent serious complications. The macroscopic anatomy of the venous sinuses of the dura mater of Alouatta belzebul was studied. Five adult specimens, males and females, were dissected and fixed in 10% formaldehyde solution. In the dura mater of the Alouatta belzebul, nine venous sinuses were observed, being them dorsal sagittal sinus, ventral sagittal sinus, transverse sinus, straight sinus, sigmoid sinus, temporal sinus, parietal sinus, basilar sinus and cavernous sinus, with morphological similarities in origin, path and destination of blood flow to the internal jugular vein, assisting in the venous drainage function of the brain in this species. These data are similar to those found in other species of non-human and human primates such as Saimiri sciureus, Sapajus libidinosus and Homo sapiens. Of the venous sinuses observed, the cavernous sinus was of considerable clinical and surgical importance in Alouatta belzebul due to its topographic arrangement next to the internal carotid artery and pituitary gland, data that corroborate Sapajus libidinosus, Macaca fascicularis, Macaca mulatta, Papio ursinus, Cercopithecus pygerithrus and Galago senegalensis. In this context, the knowledge of the macroscopic anatomy of the venous sinuses of the dura mater may contribute to the role of veterinarians in less invasive surgical procedures in non-human primates such as Alouatta belzebul and other mammals.
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Alouatta/anatomia & histologia , Cavidades Cranianas/anatomia & histologia , Dura-Máter/anatomia & histologia , Animais , Encéfalo/irrigação sanguínea , Feminino , Masculino , Especificidade da EspécieRESUMO
Isoflavone is a phytoestrogen found in different types of food that can act as endocrine disrupters leading to testicular dysfunction. Currently, fragmented data on the action of this compound in the testicles make it difficult to assess its effects to define a safe dose. Thus, we systematically reviewed the preclinical evidence of the impact of isoflavone on testicular function. We also determined which form (aglycones or glycosylated) was the most used, which allowed us to understand the main biological processes involved in testicular function after isoflavone exposure. This systematic review was carried out according to the PRISMA guidelines using a structured search on the biomedical databases MEDLINE (PubMed), Scopus, and Web of Science, recovering and analyzing 22 original studies. The bias analysis and the quality of the studies were assessed by the criteria described in the risk of bias tool developed by SYRCLE (Systematic Review Centre for Laboratory Animal Experimentation). The aglycones and glycosylated isoflavones proved to be harmful to the reproductive health, and the glycosylates at doses of 50, 100, 146, 200, 300, 500, and 600 mg/kg, in addition to 190 and 1000 mg/L, appear to be even more harmful. The main testicular pathologies resulting from the use of isoflavones are associated with Leydig cells resulting from changes in molecular functions and cellular components. The most used isoflavone to evaluate testicular changes was the genistein/daidzein conjugate. The consumption of high doses of isoflavones promotes changes in the functioning of Leydig cells, inducing testicular changes and leading to infertility in murine models.
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The toxic effects of cadmium (Cd) on hepatic parameters are widely described in the literature. Experimental models often make use of the intraperitoneal route (i.p.) because it is easier to apply, while in the oral route, Cd poisoning in humans is best represented by allowing the metal to pass through the digestive system and be absorbed into the bloodstream. Thus, this study investigated the Cd exposure impact on the liver, by comparing both i.p. and oral routes, both in single dose, in addition to the oral route in fractional doses. Swiss adult male mice received CdCl2 1.5 mg/kg i.p., 30 mg/kg oral single dose, and 4.28 mg/kg oral route in fractional doses for 7 consecutive days. Cd bioaccumulation was observed in all animals exposed to Cd. Hepatic concentrations of Ca and Fe increased only in the fractionated oral route. Liver activities of SOD and CAT increased only by oral single dose. GST decreased in all forms of oral administration, while MDA decreased only in i.p. route. Liver weight and HSI increased in the i.p. route, while organ volume increased in all forms of oral administration, and liver density increased in all animals exposed to Cd. In hepatic histomorphometry, the changes were more evident in oral administration, mainly in exposure to metal in a single dose. Thus, the subacute administration of Cd in different routes of administration leads to different changes in liver poisoning.
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Cádmio , Estresse Oxidativo , Administração Oral , Animais , Cádmio/metabolismo , Cádmio/toxicidade , Cloreto de Cádmio/toxicidade , Fígado/metabolismo , Masculino , Camundongos , Tamanho do ÓrgãoRESUMO
Philander frenatus is an important marsupial for the maintenance and conservation of the Atlantic Rainforest, however, it has biological characteristics that are still little explored. The study of the reproductive biology is an important key to understand the species reproductive strategies and to improve the development of conservation and management activities. The present study aimed to conduct a histological and morphometric investigation of the testis structure and function of P. frenatus. The average body and testicular weight were 445 g and 0.74 g, respectively, with a gonadosomatic index of 0.17%. The seminiferous tubules occupying 64.95% of the organ, totalising 9.26 m per gram of testis. The tubulesomatic and epitheliumsomatic indexes were 0.10% and 0.07%, respectively. Philander frenatus showed cell loss of approximately 98% during the proliferative phase and the spermatogenic yield was 10.3 cells. The high loss during the mitotic phase contributed to the low spermatogenic yield. The testicular parenchyma was composed of 35% of intertubular components, one of the highest proportions observed in mammals. Leydig cells were responsible for approximately 25% of the testes, followed by lymphatic space (6.44%), blood vessels and connective tissue (4% together). The organisation of the intertubular components resembles the Fawcett III category. The volume and number of Leydig cell per gram of testis were 2,627.12 µm3 and 91.28 × 106 cells, respectively. High investment in the intertubular compartment, specifically number and volume of Leydig cells in P. frenatus is consistent with territorial behaviour and polygynic mating system, which have greater androgenic capacity.
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Marsupiais , Testículo , Animais , Células Intersticiais do Testículo , Masculino , Gambás , Túbulos Seminíferos , Células de Sertoli , EspermatogêneseRESUMO
Glutamine is often used to treat metabolic changes associated with anorexia-cachexia syndrome in patients with malignant neoplasms. Walker 256 tumor is an excellent model for studying these changes associated with cancer in different organs, including injuries in testicular functions. However, the effects of supplementing glutamine on testicular morphometry in this model have not yet been investigated. Thus, the objective of this study was to evaluate the effect of L-glutamine supplementation on testicular morphometry in rats transplanted with Walker 256 tumor cells. Forty puberty Wistar rats were divided into four groups: control without L-glutamine (C); control supplemented with L-glutamine (CG); inoculated with Walker 256 tumor cells (WT) and inoculated with Walker 256 tumor cells and supplemented with L-glutamine (WTG). The testicles were removed, weighed, fixed in Bouin, and included in paraffin for histomorphometric analysis. Walker 256 tumor caused quantitative changes in the tubular and intertubular compartments and tunica albuginea, with reductions in the percentages of lumen and tunica albuginea, number of Sertoli cells per gram of testis; number of Leydig cells; percentage of blood vessels and connective tissue in intertubule. However, glutamine supplementation prevented part of these changes caused by the tumor, presenting mainly a protective effect on the tunica albuginea and percentage of blood and lymph vessels in the intertubule. These results indicate the potential of L-glutamine was able to recover for testicular dysfunction associated with cancer.
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ETHNOPHARMACOLOGICAL RELEVANCE: Scientific evidence supports the antioxidant, anti-inflammatory and anti-lipidemic properties of Euterpe oleracea Mart. (açaí), which all converge to reduce cardiovascular risks. Macerating the pulp of açaí fruit produces a viscous aqueous extract (AE) rich in flavonoids that is commonly used in food production. In addition to nutritional aspects, cardiovascular benefits are attributed to AE by traditional medicine. AIM OF THE STUDY: Evaluation of AE impact on blood flow in vivo in rats and investigation of the mechanism underlying this response in vitro in rat endothelial cells (RECs). MATERIALS AND METHODS: For the measurement of acute blood flow, a perivascular ultrasound probe was used in Wistar rats. The in vitro assays employed REC to evaluate: concentration (1-1000 µg/mL) and time response (2-180 min) of AE in MTT cell viability assays; nitric oxide (NO) levels measurement and intracellular calcium handling using DAF-2DA and Fluo-4-AM, respectively; cellular biopterin content by HPLC; activation of Akt pathway using western blot analysis. For the chemical analyses of AE, stock solutions of the standards (+)catechin and quercetin were used for obtaining linear calibration curves. Identification and quantification of flavonoids in AE were based on comparisons with the retention times, increase in peak area determine by co-injection of AE with standards, UV-Vis scan and standard curves of known spectra. Results were expressed as mean ± standard deviation and data were analyzed using ANOVA followed by Tukey's post-test (p < 0.05). RESULTS: Although in vivo data have revealed the participation of NO in increasing of acute blood flow on abdominal aorta, in vitro analysis demonstrated that vasodilatation AE-induced is not related to its direct action on endothelial cells inducing eNOS activation. Besides, we demonstrated in isolated endothelial cells that highest concentrations of AE caused a reduction in NO levels, effect that could be partly justified by inhibition of Akt phosphorylation which, in turn, could decrease NOS activation. The involvement of cell transduction pathways involving variations in intracellular calcium and biopterins concentration were discarded. The participation of catechin and quercetin, identified in AE, was postulated to induce the responses of AE in REC. CONCLUSIONS: Despite the responses in vitro, vasodilation prevailed in vivo, probably by activating intermediate pathways, validating a potential beneficial effect of AE in reducing cardiovascular risks.
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Circulação Sanguínea/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Euterpe/química , Extratos Vegetais/farmacologia , Animais , Biopterinas/metabolismo , Cálcio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Frutas/química , Masculino , Óxido Nítrico/metabolismo , Extratos Vegetais/uso terapêutico , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Wistar , Vasodilatação/efeitos dos fármacos , Água/químicaRESUMO
Deregulation of miRNAs contributes to the development of distinct cancer types, including melanoma, an aggressive form of skin cancer characterized by high metastatic potential and poor prognosis. The expression of a set of 580 miRNAs was investigated in a model of murine melanoma progression, comprising non-metastatic (4C11-) and metastatic melanoma (4C11+) cells. A significant increase in miR-138-5p expression was found in the metastatic 4C11+ melanoma cells compared to 4C11-, which prompted us to investigate its role in melanoma aggressiveness. Functional assays, including anoikis resistance, colony formation, collective migration, serum-deprived growth capacity, as well as in vivo tumor growth and experimental metastasis were performed in 4C11- cells stably overexpressing miR-138-5p. miR-138-5p induced an aggressive phenotype in mouse melanoma cell lines leading to increased proliferation, migration and cell viability under stress conditions. Moreover, by overexpressing miR-138-5p, low-growing and non-metastatic 4C11- cells became highly proliferative and metastatic in vivo, similar to the metastatic 4C11+ cells. Luciferase reporter analysis identified the tumor suppressor Trp53 as a direct target of miR-138-5p. Using data sets from independent melanoma cohorts, miR-138-5p and P53 expression were also found deregulated in human melanoma samples, with their levels negatively and positively correlated with prognosis, respectively. Our data shows that the overexpression of miR-138-5p contributes to melanoma metastasis through the direct suppression of Trp53.
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Regulação Neoplásica da Expressão Gênica , Melanoma/genética , Melanoma/mortalidade , MicroRNAs/genética , Interferência de RNA , Proteína Supressora de Tumor p53/genética , Regiões 3' não Traduzidas , Animais , Linhagem Celular Tumoral , Humanos , Melanoma/patologia , Camundongos , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Análise de SobrevidaRESUMO
OBJECTIVE: To systematically review the literature regarding the microbiota composition in various peri-implant conditions as analyzed by 16S rRNA gene sequencing methods. METHODS: Electronic searches were conducted at MEDLINE/PubMed, Scopus, Embase, ScienceDirect and Web of Science databases looking for articles published up to April 2020. Observational prospective investigations were considered with systemically healthy patients and that had presented the description of the microbiota composition of peri-implantitis (PI), peri-implant mucositis (PM) and/or health implants (HI) by using 16S rRNA gene sequencing analysis were considered eligible. RESULTS: From 1,380 titles found, 8 studies were considered for qualitative analysis. One article was excluded due to high risk of bias, remaining 7 studies for descriptive analysis. In 6 out of 7 studies the PI microbiota was reported as being in relative abundance and variety though with a different composition from those with HI. There was no consensus regarding which condition had more diversity. The main observed phyla among PI were Firmicutes, Bacteroidetes, Actinobacteria, Fusobacteria and Spirochaetes, while the genera were mainly Actinomyces, Eubacterium, Fusobacterium, Mogibacterium, Moraxella, Treponema and Porphyromonas. Comparisons between PI and PM microbiota showed conflicting results: one study suggested that PI has greater bacterial diversity; another study reported the opposite result, while another investigation found similar variety for both conditions. CONCLUSIONS: The microbiota of peri-implant conditions have been reported as distinct, although the available literature presents discrepancies. Nonetheless, considering the findings in most studies, it can be suggested that the relative abundance of microbiota and bacterial diversity increased with the progress of peri-implant disease.
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Implantes Dentários/microbiologia , Microbiota , Peri-Implantite/microbiologia , Bactérias/classificação , Humanos , Estudos Observacionais como Assunto , RNA Ribossômico 16SRESUMO
This study aimed to compare Cd exposure by intraperitoneal (i.p.) and oral routes, evaluating the testicular subacute and subchronic effects. Adult male mice were separated into three groups subdivided according to the experimental period (7 and 42 days after Cd exposure: subacute and subchronic effects, respectively): one group received water and two groups received CdCl2 (1.2 mg/kg i.p. and 24 mg/kg oral). The testicular concentration of essential minerals and Cd, activity of antioxidant enzymes and markers of oxidative stress, histology, and testicular histomorphometry were evaluated. The subacute effect of oral Cd showed reduced Fe concentration, while Ca and Cu increased in this route. The subchronic effect promoted decreasing in Mg in i.p. and oral routes, whereas Zn decreased only in the oral, and the Fe concentration did not change. SOD activity decreased in the oral subacute evaluation and in both pathways, i.p. and oral routes, in the subchronic evaluation, while GST activity increased, and MDA concentration decreased. Labeling of apoptotic cells was increased in the subacute and subchronic evaluation. Seminiferous epithelium degeneration, death of germ cells, and Leydig cell damages occurred in i.p. and oral routes. However, these damages were more intense in the oral route, mainly evaluating the subchronic effects. The results confirm that the severity of Cd-induced testicular injury depends on the pathway, as well as the duration of exposure.
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Cádmio/toxicidade , Testículo/efeitos dos fármacos , Testes de Toxicidade Subaguda/métodos , Testes de Toxicidade Subcrônica/métodos , Administração Oral , Animais , Cádmio/administração & dosagem , Cálcio/metabolismo , Catalase/metabolismo , Cobre/metabolismo , Injeções Intraperitoneais , Ferro/metabolismo , Magnésio/metabolismo , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Testículo/metabolismo , Testículo/patologia , Zinco/metabolismoRESUMO
Cadmium (Cd) is an environmental pollutant that induces reproductive toxicity by generating reactive oxygen species, which leads to oxidative stress. Euterpe oleracea fruits are known for being rich in oils containing triacylglycerol and phenolic compounds. They are considered as potent antioxidants to be used to counteract Cd effects within the testis. In the present study, adult males Swiss mice were treated with CdCl2 aqueous solution (4.28 mg/kg) by gavage for 7 days. The experimental groups were treated with Euterpe oleracea oil at the doses of 50, 100, and 150 mg/kg, for 42 days. The results showed that Cd intoxication led to increased tubular pathologies, such as reduction in epithelium height and area thus increasing both luminal diameter and tubule-epithelium ratio. Besides, Leydig cell's morphometry indicated reduction in nucleus and cytoplasm volumes of this cell type, which were recovered after E. oleracea oil intake. In addition, serum testosterone levels, testicular Mn and Zn concentrations, SOD and CAT activity, and germ cell viability increased after oil intake. Therefore, E. oleracea oil showed a regenerative effect in the testicular parenchyma negatively affected by Cd, mainly in the animals that received the highest oil concentration (150 mg/kg).
Assuntos
Euterpe , Animais , Antioxidantes , Cádmio/toxicidade , Masculino , Camundongos , Óleos , Estresse Oxidativo , TestículoRESUMO
ETHNOPHARMACOLOGICAL USAGES: Leaves and roots of Pfaffia glomerata areused as aphrodisiacs, tranquilizers and antirheumatics. Due to the lack of experimental scientific data, studies are necessary to identify its medicinal properties. AIMS: The present study aimed to evaluate the effect of hydroalcoholic root extract of P. glomerata (Brazilian ginseng extract - BGE) on testicular parenchyma, and evaluate possible harmful effects through testicular oxidative stress analysis. MATERIALS AND METHODS: Adult mice were divided into 6 groups: control (water), sildenafil citrate, BGE (100, 200 and 400â¯mg/kg/day), and BGE (200â¯mg/kg every three days). RESULTS: The treatment reduced the volumetric proportions of seminiferous tubules and epithelium, the number of Sertoli cells, and increased hydrogen peroxide levels, without affecting sperm production. It also caused cell death and changes in the frequency of stages of the seminiferous epithelium cycles. The 100â¯mg/kg dose responds in a similar way to sildenafil citrate, promoting changes in the gonadal structure, but with efficient response to contain the damage. CONCLUSIONS: Doses of 200â¯mg/kg, continuous or discontinuous, induced an increase in testicular nitric oxide, as well as sildenafil citrate, showing be efficient as aphrodisiac, but promotes cell death regardless of the form of administration.