The antineoplastic potential of crotoxin isolated from Crotalus durissus terrificus snake venom on oral squamous cell carcinoma.

This study investigated the antineoplastic effects of crotoxin isolated from snake venom of the South American Crotalus durissus terrificus in oral cancer cell lines and in an animal model of chemically induced oral cancer. We analyzed cell viability and death, clonogenic formation, DNA fragmentation, migration assay, and gene expression of MMP2, MMP9, COL1A1, and CASP3. In the animal model, after induction of oral cancer by 4-nitroquinoline-1-oxide carcinogen, mice were treated with crotoxin to investigate its effects on tumor development in tongue and oral mucosa. Crotoxin inhibited cell proliferation, viability, colony formation, and migration, favoring cell death. Furthermore, crotoxin increased caspase-3 expression, decreased Ki-67 protein and mRNA expression of MMP2, MMP9, and COL1A1. Mice treated with crotoxin at 10 µg/kg did not alter biochemical parameters total cholesterol, very-low-density lipoprotein, high-density lipoprotein, liver transaminases, glycemia, creatinine, and urea. Crotoxin treatment significantly reduced the frequency of oral squamous cell carcinoma lesions by 50%. Thus, this study highlights crotoxin as a promising chemotherapeutic substance, considering its effects on controlling the neoplastic cell population, reducing cell migration, and inhibiting tumor development. Clinical studies are necessary to understand better the impact of crotoxin as a potential adjuvant therapeutic agent for oral cancer patients.

Gallic acid has an inhibitory effect on skin squamous cell carcinoma and acts on the heat shock protein HSP90AB1.

Differences in the features of aggressiveness of non-melanoma skin cancer (NMSC) subtypes, between basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are relevant characteristics. Comparing the characteristics between NMSC subtypes might help identify molecules associated with cancer metastasis and invasion. Considering these facts, the current study aimed to identify a molecular target for inhibiting skin cancer metastasis and invasion. Proteomic analysis suggested that heat shock protein 90 kDa, alpha, class B member 1 (HSP90AB1), pentaxin (PTX3), caspase-14 (CASP14), S100, actin-1, and profilin were the primary targets related to metastasis and invasion. However, after a differential expression comparison between BCC and SCC, HSP90AB1 was identified as the best target to repress metastasis and invasion. Based on molecular docking results, gallic acid (GA) was selected to inhibit HSP90AB1. A specific Hsp90ab1 siRNA targeting was designed and compared to GA. Interestingly, GA was more efficient in silencing HSP90AB1 than siRNAhsp90ab1. Hence, our data suggest that HSP90AB1 is a crucial biomarker for identifying invasion and metastasis and that its inhibition may be a viable strategy for treating skin cancer.

Acute oral treatment with resveratrol and Lactococcus Lactis Subsp. Lactis decrease body weight and improve liver proinflammatory markers in C57BL/6 mice.

The present study aimed to evaluate the effects of resveratrol, a nutraceutical polyphenol, and Lactococcus lactis (bacteria probiotic), on metabolic parameters and hepatic proinflammatory markers expression. C57BL/6 mice were divided into 4 groups: Standard (ST), Lactococcus lactis (LL), Resveratrol (RSV), and Lactococcus lactis plus resveratrol (LL + RSV). Lactococcus lactis and resveratrol were administered by orogastric gavage. Blood parameters were assessed (total cholesterol, triglycerides, ALT and AST). IL-6 mRNA expression was evaluated by Real-time PCR and TNF-α protein expression was assessed by immunohistochemistry. The main findings showed that resveratrol and Lactococcus lactis association decreased body weight, aspartate aminotransferase and total cholesterol levels. LL and LL + RSV decreased triglycerides levels and IL-6 and TNF-α expression. These results open a perspective of using resveratrol and Lactococcus lactis to improve metabolic parameters and Lactococcus lactis in preventing inflammation and the hepatic diseases development.

Hydroalcoholic Extract of Solanum lycocarpum A. St. Hil. (Solanaceae) Leaves Improves Alloxan-Induced Diabetes Complications in Mice.

BACKGROUND: Solanum lycocarpum is a medicinal plant used in Brazil with hypoglycemic activity by its fruits use. However, the fruits production is restricted in some periods of the year, differently of leaves. OBJECTIVE: To evaluate the effects of hydroalcoholic extracts of S. lycocarpum leaves in alloxan-induced diabetic mice. METHODS: Hydroalcoholic extract of S. lycocarpum was characterized by phytochemical and GCMS analysis. The Antidiabetic activity was assessed following treatment for 22 days with S. lycocarpum extract at 125, 250, and 500 mg/kg. Bodyweight, water, and food intake, glycemia, biochemical parameters, anatomy-histopathology of the pancreas, liver and kidney, and expression of target genes were analyzed. In addition, oral acute toxicity was evaluated. RESULTS: Animals treated showed a significant reduction (p < 0.05) in glycemia following a dose of 125 mg/kg. Food intake remained similar for all groups. Decreased polydipsia symptoms were observed after treatment with 250 (p < 0.001) and 500 mg/kg (p < 0.01) compared with diabetic control, although normal rates were observed when 125 mg/kg was administered. A protective effect was also observed in the pancreas, liver, and kidneys, through the regeneration of the islets. Hypoglycemic activity can be attributed to myo-inositol, which stimulates insulin secretion, associated with α-tocopherol, which prevents damage from oxidative stress and apoptosis of ß-pancreatic cells by an increased Catalase (CAT) and Glutathione peroxidase 4 (GPX4) mRNA expression. The toxicological test demonstrated safe oral use of the extract under the present conditions. CONCLUSION: Hydroalcoholic extract of S. lycocarpum promotes the regulation of diabetes in the case of moderate glycemic levels, by decreasing glycemia and exerting protective effects on the islets.

Radiation Therapy Reduced Blood Levels of LDH, HIF-1α, and miR-210 in OSCC.

Radiation Therapy (RT) is a treatment option for a large number of neoplasias. However, the effect of RT on the level of hypoxia markers is poorly understood. The present study aimed to investigate the effect of RT on the levels of hypoxic markers in Oral squamous cell carcinoma (OSCC). Evaluation of HIF-1α and miR-210 levels in OSCC was performed. Then a proteomic analysis was performed to identify candidate hypoxic targets of RT. To validate proteomic studies, the effect of RT on HIF-1α, miR-210, PDH-A and LDH-A levels under hypoxia was assessed by qRT-PCR. The impact of RT in hypoxia markers was evaluated in patients to confirm in vitro results. An increase in the HIF-1α levels was observed in OSCC. RT reduced OSCC cell proliferation and migration. Interestingly, hypoxia could revert the effect of radiation on OSCC phenotype. However, proteomics analyses suggested that LDH is one of the critical targets of RT even in hypoxia. Moreover, RT decreased HIF-1α, miR-210, and LDH even in hypoxia. The current study demonstrated that hypoxia could revert the effects of RT in the OSCC context. However, RT reduces the levels HIF-1α, miR-210 and LDH in vivo and in vitro. The consequences of RT in blood should be carefully investigated.

Conditioned fear stress increases bone resorption in apical periodontitislesions in Wistar male rats.

OBJECTIVE: Because the impact of conditioned fear stress on apical bone resorption is unknown, the aim of the current studywas to use a rat model to evaluate the impact of conditioned fear stress on the bone resorption of inflammatory apical periodontitis lesions. METHODS: Twenty-five animals were divided into two groups. They underwent a surgical procedure in the first left lower molar tooth to expose the dental pulp and induce inflammatory apical periodontitis lesions through the retention of contamination (bacterial infection) during a 56-day period. The animals in the case group were stressed daily by using electrical stimuli (1.10 mA), whereas the animals in the control group were absent from the stressful stimuli (shocks). The open field test was performed to validate the stress methodology. The jaws were removed and collected for histological and radiographic analyses. RESULTS: Stressed animals presented increased levels of bone loss and inflammatory cells in the root apex in comparison with the control group (P = 0.0001). However, no radiographic differences were observed between the groups (P > 0.05). CONCLUSIONS: Our results demonstrated that conditioned fear stress could modify a periapical lesion by increasing the size of bone loss there. Conditioned fear stress also increased the total number of inflammatory cells compared with the control group. Studies evaluating the impact of conditioned fear stress on human periapical inflammatory lesions should be encouraged.

Gallic acid modulates phenotypic behavior and gene expression in oral squamous cell carcinoma cells by interfering with leptin pathway.

Gallic acid is a polyphenolic compost appointed to interfere with neoplastic cells behavior. Evidence suggests an important role of leptin in carcinogenesis pathways, inducing a proliferative phenotype. We investigated the potential of gallic acid to modulate leptin-induced cell proliferation and migration of oral squamous cell carcinoma cell lines. The gallic acid effect on leptin secretion by oral squamous cell carcinoma cells, as well as the underlying molecular mechanisms, was also assessed. For this, we performed proliferation, migration, immunocytochemical and qPCR assays. The expression levels of cell migration-related genes (MMP2, MMP9, Col1A1, and E-cadherin), angiogenesis (HIF-1α, mir210), leptin signaling (LepR, p44/42 MAPK), apoptosis (casp-3), and secreted leptin levels by oral squamous cell carcinoma cells were also measured. Gallic acid decreased proliferation and migration of leptin-treated oral squamous cell carcinoma cells, and reduced mRNA expression of MMP2, MMP9, Col1A1, mir210, but did not change HIF-1α. Gallic acid decreased levels of leptin secreted by oral squamous cell carcinoma cells, accordingly with downregulation of p44/42 MAPK expression. Thus, gallic acid appears to break down neoplastic phenotype of oral squamous cell carcinoma cells by interfering with leptin pathway.

Aproximações e distanciamentos nos pensamentos de Feuerbach eJung / Similarities and differences in the thoughts of Feuerbach and Jung

O presente artigo tem por objetivo apresentar as perspectivas de Feuerbach e Jung sobre o fenômeno religioso. Tal análise torna-se importante pelo fato de que ambas as teorias contribuem significativamente para entendimento desse fenômeno, tanto pelo campo da Filosofia quanto da Psicologia. Deste modo, o artigo se desenvolverá em três partes:primeiramente, as concepções de Feuerbach sobre o fenômeno religioso, posteriormente as reflexões de Jung e, por fim, a identificação de aproximações e distanciamentos entre eles referentes ao fenômeno religioso.(AU)

The aim of this article is to present the perspectives of Feurebach and Jung concerning the religious phenomenon. The importance of this analysis lies in the fact that both theories contribute significantly to the understanding of this phenomenon, in the field of philosophy as well as psychology. Thus, the article develops into three parts: first, the views of Feuerbach about the religious phenomenon, then Jung's reflections on the subject, and finally the identification of similarities and differences between them.(AU)

Aproximações e distanciamentos nos pensamentos de Feuerbach e Jung / Similarities and differences in the thoughts of Feuerbach and Jung

O presente artigo tem por objetivo apresentar as perspectivas de Feuerbach e Jung sobre o fenômeno religioso. Tal análise torna-se importante pelo fato de que ambas as teorias contribuem significativamente para entendimento desse fenômeno, tanto pelo campo da Filosofia quanto da Psicologia. Deste modo, o artigo se desenvolverá em três partes: primeiramente, as concepções de Feuerbach sobre o fenômeno religioso, posteriormente as reflexões de Jung e, por fim, a identificação de aproximações e distanciamentos entre eles referentes ao fenômeno religioso.(AU)

The aim of this article is to present the perspectives of Feurebach and Jung concerning the religious phenomenon. The importance of this analysis lies in the fact that both theories contribute significantly to the understanding of this phenomenon, in the field of philosophy as well as psychology. Thus, the article develops into three parts: first, the views of Feuerbach about the religious phenomenon, then Jung's reflections on the subject, and finally the identification of similarities and differences between them.(AU)

Do Círculo de Eranos à construção do simbólico, em Carl Gustav Jung / From Eranos Circle to the symbolic construction in Carl Gustav Jung / Du Cercle d'Eranos à la construction du symbolique chez Carl Gustav Jung / Del Círculo de Eranos a la construcción del simbólico, en Carl Gustav Jung

O artigo discute a origem e a extensão do Círculo de Eranos e sua importância na compreensão do simbólico, estabelecendo a compreensão da construção do simbólico como tentativa de união entre Oriente e Ocidente em C. G. Jung.(AU)

The article discusses the origin and extent of the Eranos Circle and its importance in understanding the symbolic, establishing the comprehension of the symbolic construction as an attempt to unite East and West in C. G. Jung.(AU)

Cet article discute l'origine et l'extension du Cercle d'Eranos, et son importance pour la compréhension du symbolique. Ce travail vise à établir une compréhension de la construction du symbolique comme une tentative de l'union de l'Orient et l'Occident dans la pensée de C. G. Jung.(AU)

Este artículo discute el origen y la extensión del Círculo de Eranos, así como su importancia para la comprensión del simbólico. Su objetivo es establecer la comprensión de la construcción del simbólico como tentativa de unión entre Oriente y Occidente en C. G. Jung.(AU)

Do Círculo de Eranos à construção do simbólico, em Carl Gustav Jung / From Eranos Circle to the symbolic construction in Carl Gustav Jung / Du Cercle d'Eranos à la construction du symbolique chez Carl Gustav Jung / Del Círculo de Eranos a la construcción del simbólico, en Carl Gustav Jung

O artigo discute a origem e a extensão do Círculo de Eranos e sua importância na compreensão do simbólico, estabelecendo a compreensão da construção do simbólico como tentativa de união entre Oriente e Ocidente em C. G. Jung...

The article discusses the origin and extent of the Eranos Circle and its importance in understanding the symbolic, establishing the comprehension of the symbolic construction as an attempt to unite East and West in C. G. Jung...

Cet article discute l'origine et l'extension du Cercle d'Eranos, et son importance pour la compréhension du symbolique. Ce travail vise à établir une compréhension de la construction du symbolique comme une tentative de l'union de l'Orient et l'Occident dans la pensée de C. G. Jung...

Este artículo discute el origen y la extensión del Círculo de Eranos, así como su importancia para la comprensión del simbólico. Su objetivo es establecer la comprensión de la construcción del simbólico como tentativa de unión entre Oriente y Occidente en C. G. Jung...

Avaliação do conhecimento dos residentes de um programa de residência multiprofissional em saúde referente ao contrato didático

Este estudo teve como objetivo analisar as relações de ensino e aprendizagem, nos espaços de formação em saúde, através da avaliação do conhecimento dos residentes de um Programa de Residência Multiprofissional em Saúde, no que se refere ao Contrato Didático, sua importância , bem como sua participação na elaboração das regras que norteiam essas relações, Foi realizada uma pesquisa com abordagem quantitativa e qualitativa. Primeiramente, foi aplicado um questionário, junto aos residentes de primeiro ano (R1) das ênfases da Residência Integrada do Grupo Hospitalar Conceição, a saber: Atenção ao Paciente Crítico, Oncologia e Hematologia, Saúde Mental, Saúde da Família e Comunidade. Posteriormente, dez residentes, que participaram da da primeira fase, foram convidados para integrarem um grupo, que foi submetido a entrevistas semi-estruturadas, gravadas, a fim de que fossem aprofundadas as questões sobre a temática do estudo. Através de análise das respostas, foi possível compreender como se estruturam as relações nos espaços de ensino e aprendizagem em serviço da RIS/GHC, o conhecimento dos residentes com relação ao Contrato Didático, e como sentem sua participação na elaboração de regras que normatizam a sua formação em serviço na Residência. A análise possibilitou também perceber as dúvidas e os anseios dos residentes, bem como sua percepção sobre a relação didática. Embora alguns residentes tenham referido conhecer aspectos sobre Contrato Didático, eles não se sentem participantes ativos espaços de discussão e nas decisões tomadas em relação ao processo de formação, o que implica a necessidade de uma permanente revisão de práticas e conceitos, de modo que os saberes formalmente constituídos oportunizem debates que incluam os temas aprendizagem e ação docente, pois é o Contrato Didático que poderá possibilitar algumas das respostas necessárias para os rumos do processo de ensino e aprendizagem nos e´paços de formação existentes.