The possibilities and implications of photons within the infrared, visible, and ultraviolet behaving as sources of intracellular and intercellular communication and information were investigated experimentally for melanoma cells during the 24 hrs following removal from incubation. Specific wavelengths during different intervals were associated with specific classes of biomolecules that were predicted based on the physical properties associated with their amino acid sequences. Application of a specific intensity and physiologically patterned magnetic field predicted from a model that applied the concept of magnetic moment to the whole cell resulted in photon emissions. They were detected at distances sufficient to allow intercellular communication. The occurrence of macroscopic entanglement or non-locality was shown between two loci of where simple chemically-based photons emissions were generated. Within all three experiments there was marked quantitative congruence between the energies associated with the power density of the photon emissions and the physicochemical variables involved with their reduction. These results indicate that photon emissions coupled with classic biomolecular pathways and processes may behave as intra- and inter-cellular sources of information that could control the complex dynamics of cells. The effect may not depend upon locality but exhibit non-local characteristics.

Indiana University-Purdue University Indianapolis (IUPUI) / Glucocorticoid excess is a leading cause of osteoporosis. The loss of bone mass and strength corresponds to the increase in fractures exhibited after three months of glucocorticoid therapy. Glucocorticoids induce the bone cellular responses of deceased bone formation, increased osteoblast/osteocyte apoptosis, and transient increased bone resorption, which result in rapid bone loss and degradation of bone microarchitecture. The current standard of care for osteoporosis is bisphosphonate treatment; however, these agents further suppress bone formation and increase osteonecrosis and low energy atypical fracture risks. Thus, there is an unmet need for interventions that protect from glucocorticoid therapy. The purpose of these studies was to investigate novel mechanisms that potentially interfere with glucocorticoid-induced bone loss. We chose to explore pathways that regulate endoplasmic reticulum stress, the canonical Wnt pathway, and Pyk2 activity. Pharmacologic reduction of endoplasmic reticulum stress through salubrinal administration protected against glucocorticoid-induced bone loss by preservation of bone formation and osteoblast/osteocyte viability. In contrast, inhibition of Wnt antagonist Sost/sclerostin and inhibition of Pyk2 signaling did not prevent glucocorticoid-induced reductions in bone formation; however, both Sost/sclerostin and Pyk2 deficiency protected against bone loss through inhibition of increases in resorption. Overall, these studies demonstrate the significant contributions of reductions in bone formation, increased osteoblast/osteocyte apoptosis, and elevations in resorption to the rapid 6-12% bone loss exhibited during the first year of glucocorticoid therapy. However, glucocorticoid excess also induces skeletal muscle weakness, which is not reversed by bisphosphonate treatment or the interventions reported here of salubrinal, Sost/sclerostin inhibition, or Pyk2 deficiency. Further, the novel finding of increased E3 ubiquitin ligase atrophy signaling induce by glucocorticoids in both bone and muscle, by tissue-specific upstream mechanisms, provides opportunities for therapeutic combination strategies. Thus, future studies are warranted to investigate the role of E3 ubiquitin ligase signaling in the deleterious glucocorticoid effects of bone and muscle.

Orientador: Winston Bonetti Yoshida / Resumo: Introdução: O Angiossarcoma (AS) é um tumor vascular maligno raro. As vias moleculares associadas ao desenvolvimento e progressão do AS ainda são pouco entendidas. miRNAs são moléculas reguladoras da expressão gênica com papel importante na tumorigênese e constituem biomarcadores em potencial, podendo definir prognóstico e tratamento de pacientes com câncer. A identificação de perfis de expressão de miRNAs e das vias moleculares reguladas por miRNAs pode contribuir para a elucidação dos mecanismos de tumorigênese em AS. Objetivos: Identificação da expressão global de miRNAs e vias moleculares em AS. Identificar miRNAs alterados em AS; identificar genes-alvo regulados pelos miRNAs e mapear miRNAs e genes alvo relacionados ao desenvolvimento vascular. Material e Métodos: Realizamos uma meta-análise segundo a Declaração de Prisma e utilizando as principais bases de dados, PubMed e EMBASE. Após a aplicação de critérios de inclusão e exclusão específicos, um estudo (incluindo 5 amostras de AS) foi considerado elegível e selecionado para extração dos dados. Deste, foram identificados os miRNAs significativamente desregulados (FC>=1,5 e p<0,05). A seguir, os dados de expressão de miRNAs foram analisados utilizando as ferramentas de bioinformática miRWalk v.2.0 para predição de genes-alvo regulados pelos miRNAs e STRING e Cytoscape v.3.1.1/BINGO para identificação de redes de interação (miRNAs-mRNAs-alvo) e funções biológicas, respectivamente. Resultados: 59 miRNAs estavam com expres... (Resumo completo, clicar acesso eletrônico abaixo) / Doutor