An association between mast cells and tumor angiogenesis is known to exist, but the exact role that mast cells play in this process is still unclear. It is thought that the mediators released by mast cells are important in neovascularization. However, it is not known how individual mediators are involved in this process. The major constituents of mast cell secretory granules are the mast cell specific proteases chymase, tryptase, and carboxypeptidase A3. Several previous studies aimed to understand the way in which specific mast cell granule constituents act to induce tumor angiogenesis. A body of evidence indicates that mast cell proteases are the pivotal players in inducing tumor angiogenesis. In this review, the likely mechanisms by which tryptase and chymase can act directly or indirectly to induce tumor angiogenesis are discussed. Finally, information presented here in this review indicates that mast cell proteases significantly influence angiogenesis thus affecting tumor growth and progression. This also suggests that these proteases could serve as novel therapeutic targets for the treatment of various types of cancer.
Prokaryotic genomes show a high level of information compaction often with different molecules transcribed from the same locus. Although antisense RNAs have been relatively well studied, RNAs in the same strand, internal RNAs (intraRNAs), are still poorly understood. The question of how common is the translation of overlapping reading frames remains open. We address this question in the model archaeon Halobacterium salinarum. In the present work we used differential RNA-seq (dRNA-seq) in H. salinarum NRC-1 to locate intraRNA signals in subsets of internal transcription start sites (iTSS) and establish the open reading frames associated to them (intraORFs). Using C-terminally flagged proteins, we experimentally observed isoforms accurately predicted by intraRNA translation for kef1, acs3 and orc4 genes. We also recovered from the literature and mass spectrometry databases several instances of protein isoforms consistent with intraRNA translation such as the gas vesicle protein gene gvpC1. We found evidence for intraRNAs in horizontally transferred genes such as the chaperone dnaK and the aerobic respiration related cydA in both H. salinarum and Escherichia coli. Also, intraRNA translation evidence in H. salinarum, E. coli and yeast of a universal elongation factor (aEF-2, fusA and eEF-2) suggests that this is an ancient phenomenon present in all domains of life.
Os principais dicionários da língua portuguesa trazem como significado de liga, a aliança, união, pacto. De forma similar, a físico-química nos mostra que uma liga é produto de caráter metálico resultante da incorporação de um ou de vários elementos a um metal com o objetivo precípuo de constituir soluções sólidas. Esta característica deve ou pode ter norteado a denominação original da união de acadêmicos com objetivo extracurricular comum.Todavia não há um conceito claro e bem constituído do que são as Ligas Acadêmicas. Diversas definições podem ser encontradas assim como uma variedade de objetivos e funções são estabelecidos e relacionados a elas. Apesar das primeiras ligas terem sido fundadas já há algumas décadas, ainda são escassas as publicações e os estudos sobre esse assunto, tornando ainda mais árdua uma padronização de conceitos sobre o mesmo. Sendo assim, baseado no material e estudos existentes, na troca de informações e na vivência junto às próprias Ligas Acadêmicas da Faculdade de Medicina de Ribeirão Preto, esse ponto de vista almeja discutir a importância do tema não só para a graduação médica, mas a influencia que ele tem para a formação e atuação do profissional e para comunidade, suscitando a relevância atual e as perspectivas.A primeira Liga Acadêmica, denominada Liga de Combate à Sífilis, foi criada na década de 20 do
Highlights Approximately 650,000 people will be diagnosed this year with cancers of the oral cavity and pharynx worldwide. The absence of biomarkers for the disease early detection contributes to the late diagnosis. Despite some advances with regards to treatment, overall survival has not significantly improved in decades. We have shown that increased relative mRNA expression of KLK5 to LEKTI is associated with disease’s poor outcome. This work supports the relative expression of KLK5 to LEKTI as a valuable prognostic marker.
INTRODUÇÃO: Marketing médico é um assunto controverso, principalmente no que concerne a princípios éticos. Portanto, frente à competição acirrada de mercado, é necessário o preparo profissional. Conhecer a percepção dos alunos de Medicina pode auxiliar na estruturação de alternativas de capacitação. METODOLOGIA: Inicialmente, identificaram-se crenças sobre marketing médico através de grupo focal composto por 12 alunos. Com base nesses dados, dez afirmações para avaliar atitudes foram aplicadas aos alunos de uma Faculdade de Medicina pública brasileira. RESULTADOS: Observou-se falta de clareza sobre o conceito de marketing, preocupação com princípios éticos e necessidade de marketing no mercado competitivo. Na fase de aplicação, foram obtidas 280 respostas de diversos estágios do curso. Apenas 16,8% admitiram contato com o tema. Houve clareza sobre ética em relação ao paciente, influenciada positivamente pela progressão no curso, mas houve divergência na ética entre profissionais. CONCLUSÕES: Marketing médico é uma área pouco compreendida e relegada ao currículo oculto, sendo influenciada por transposições inadequadas de métodos didáticos destinados à comunicação profissional para a população leiga. Novos métodos de ensino, como a educação tutorial, podem ser uma alternativa para lidar com essas situações.
Mast cell proteases are thought to be involved with tumor progression and neo-vascularization. However, their exact role is still unclear. The present study was undertaken to further elucidate the function of specific subtypes of recombinant mouse mast cell proteases (rmMCP-6 and 7) in neo-vascularization. SVEC4-10 cells were cultured on Geltrex® with either rmMCP-6 or 7 and tube formation was analyzed by fluorescence microscopy and scanning electron microscopy. Additionally, the capacity of these proteases to induce the release of angiogenic factors and pro and anti-angiogenic proteins was analyzed. Both rmMCP-6 and 7 were able to stimulate tube formation. Scanning electron microscopy showed that incubation with the proteases induced SVEC4-10 cells to invade the gel matrix. However, the expression and activity of metalloproteases were not altered by incubation with the mast cell proteases. Furthermore, rmMCP-6 and rmMCP-7 were able to induce the differential release of angiogenic factors from the SVEC4-10 cells. rmMCP-7 was more efficient in stimulating tube formation and release of angiogenic factors than rmMCP-6. These results suggest that the subtypes of proteases released by mast cells may influence endothelial cells during in vivo neo-vascularization.
PURPOSE:To evaluate the mitochondrial function of the remnant liver (RL) in the early phase of liver regeneration in rats after 70% partial hepatectomy (PH). METHODS: Sixty male Wistar rats (200-250g) submitted to 70% PH were divided into five groups according to the time of euthanasia and application or not of laser light: C = Control, time zero; 2 minutes, 4, 6 and 24 hours after PH. The dose of laser radiation was 22.5 J/cm 2 , wavelength of 660 nm (visible/red), in the remnant liver. We studied the respiration activated by ADP (state 3), basal mitochondrial respiration (state 4), respiratory control ratio (RCR) and mitochondrial membrane potential (MMP). RESULTS:The mitochondrial function of RL changed at 4 and 6 hours after PH, with a significant increase in state 3 and a concomitant increase in state 4 and with maintenance of RCR. MMP differed significantly between the groups biostimulated with laser radiation and the control group 4 hours after HP, with a substantial reduction in the non-laser groups. CONCLUSION: The laser light at the dose used in this study did not induce additional damage to the RL and seems to have delayed the hepatocellular metabolic overload of the remnant liver. Keywords: Laser. Liver. Hepatectomy. Mitochondria. Liver Regeneration. Rats. RESUMO OBJETIVO:Avaliar a função mitocondrial do fígado remanescente (FR) na fase precoce da regeneração hepática em ratos após hepatectomia parcial (HP) a 70%. MÉTODOS: Sessenta ratos machos Wistar (200 -250g) submetidos à HP a 70%, foram distribuídos em cinco grupos de acordo com o tempo de eutanásia e com aplicação ou não de luz laser: C= Controle,tempo zero; 2 minutos, 4, 6 e 24 horas após HP. O laser foi utilizado na dose 22.5 J/cm 2 , 660 nm, no FR.Estudou-se o estado 3 (respiração ativada por ADP), estado 4 (respiração mitocondrial basal), razão de controle respiratório,estado 3/estado 4 (RCR) e o potencial de membrana mitocondrial(PMM). RESULTADOS: A função mitocondrial do FR alterou-se no período de 4 e 6 horas após a HP com aumento significativo do estado 3 e aumento concomitante do estado 4, com manutenção da RCR. O PMM apresentou diferença significativa entre os grupos bioestimulados com laser e o controle a partir de 4 horas pós HP, com queda importante do grupo sem laser e tendência a equiparação dos valores após 24 horas. CONCLUSÃO: A luz laser, na dose utilizada no presente estudo, não induziu lesão adicional ao FR e parece ter retardado a sobrecarga hepatocelular do fígado remanescente. Descritores: Lasers. Fígado. Hepatectomia. Mitocôndria. Regeneração Hepática. Ratos. Effect of laser on the remnant liver after the first 24 hours following 70% hepatectomy in ratsActa Cirúrgica 5011 -471
Angiogenesis is a complex process that involves interactions between endothelial cells and various other cell types as well as the tissue microenvironment. Several previous studies have demonstrated that mast cells accumulate at angiogenic sites. In spite of the evidence suggesting a relationship between mast cells and angiogenesis, the association of mast cells and endothelial cells remains poorly understood. The present study aims to investigate the relationship between mast cells and endothelial cells during in vitro angiogenesis. When endothelial cells were co-cultured with mast cells, angiogenesis was stimulated. Furthermore, there was direct intercellular communication via gap junctions between the two cell types. In addition, the presence of mast cells stimulated endothelial cells to release angiogenic factors. Moreover, conditioned medium from the co-cultures also stimulated in vitro angiogenesis. The results from this investigation demonstrate that mast cells have both direct and indirect proangiogenic effects and provide new insights into the role of mast cells in angiogenesis.
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