Biomedical subjects

Miguel A Medina

Publications and source records attributed to Miguel A Medina.

5 recordsLinked to original sources

PubMed2006

Mathematical modeling of polyamine metabolism in mammals.

Polyamines are considered as essential compounds in living cells, since they are involved in cell proliferation, transcription, and translation processes. Furthermore, polyamine homeostasis is necessary to cell survival, and its deregulation is involved in relevant processes, such as cancer and neurodegenerative disorders. Great efforts have been made to elucidate the nature of polyamine homeostasis, giving rise to relevant information concerning the behavior of the different components of polyamine metabolism, and a great amount of information has been generated. However, a complex regulation at transcriptional, translational, and metabolic levels as well as the strong relationship between polyamines and essential cell processes make it difficult to discriminate the role of polyamine regulation itself from the whole cell response when an experimental approach is given in vivo. To overcome this limitation, a bottom-up approach to model mathematically metabolic pathways could allow us to elucidate the systemic behavior from individual kinetic and molecular properties. In this paper, we propose a mathematical model of polyamine metabolism from kinetic constants and both metabolite and enzyme levels extracted from bibliographic sources. This model captures the tendencies observed in transgenic mice for the so-called key enzymes of polyamine metabolism, ornithine decarboxylase, S-adenosylmethionine decarboxylase and spermine spermidine N-acetyl transferase. Furthermore, the model shows a relevant role of S-adenosylmethionine and acetyl-CoA availability in polyamine homeostasis, which are not usually considered in systemic experimental studies.

Acetyl Coenzyme A↗

PubMed2006

Hyperforin: more than an antidepressant bioactive compound?

Hyperforin is a lipophilic compound that is present in great amounts in St. John's wort and that has been described as the main responsible for the antidepressant effects of this medicinal plant. In the last few years, evidence has accumulated pointing to other different effects of hyperforin with potential pharmacological interest. They include other neurological effects, effects on inflammation, as well as antibacterial, antitumoral and antiangiogenic effects.

Angiogenesis Inhibitors↗

PubMed2006

Anti-angiogenic drugs: from bench to clinical trials.

Angiogenesis, the generation of new capillaries through a process of pre-existing microvessel sprouting, is under stringent control and normally occurs only during embryonic and post-embryonic development, reproductive cycle, and wound repair. However, in many pathological conditions (solid tumor progression, metastasis, diabetic retinopathy, hemangioma, arthritis, psoriasis and atherosclerosis among others), the disease appears to be associated with persistent upregulated angiogenesis. The development of specific anti-angiogenic agents arises as an attractive therapeutic approach for the treatment of cancer and other angiogenesis-dependent diseases. The formation of new blood vessels is a complex multi-step process. Endothelial cells resting in the parent vessels are activated by an angiogenic signal and stimulated to synthesize and release degradative enzymes allowing endothelial cells to migrate, proliferate and finally differentiate to give rise to capillary tubules. Any of these steps may be a potential target for pharmacological intervention. In spite of the disappointing results obtained initially in clinical trials with anti-angiogenic drugs, recent reports with positive results in phases II and III trials encourage expectations in their therapeutic potential. This review discusses the current approaches for the discovery of new compounds that inhibit angiogenesis, with emphasis on the clinical developmental status of anti-angiogenic drugs.

Angiogenesis Inhibitors↗

PubMed2005

Topology, tinkering and evolution of the human transcription factor network.

Patterns of protein interactions are organized around complex heterogeneous networks. Their architecture has been suggested to be of relevance in understanding the interactome and its functional organization, which pervades cellular robustness. Transcription factors are particularly relevant in this context, given their central role in gene regulation. Here we present the first topological study of the human protein-protein interacting transcription factor network built using the TRANSFAC database. We show that the network exhibits scale-free and small-world properties with a hierarchical and modular structure, which is built around a small number of key proteins. Most of these proteins are associated with proliferative diseases and are typically not linked to each other, thus reducing the propagation of failures through compartmentalization. Network modularity is consistent with common structural and functional features and the features are generated by two distinct evolutionary strategies: amplification and shuffling of interacting domains through tinkering and acquisition of specific interacting regions. The function of the regulatory complexes may have played an active role in choosing one of them.

Algorithms↗

PubMed2003

Homocysteine is a potent inhibitor of human tumor cell gelatinases.

Extracellular matrix-degrading gelatinases are mainly involved in tumor invasion and metastasis. Previous experimental data from our group and others suggested that homocysteine could have a potential modulatory role on the proteolytic balance at the extracellular matrix. Therefore, we studied the effects of homocysteine on extracellular matrix-degrading proteases using model human tumor cell lines and a combination of in vitro fluorogenic assay and zymographic techniques. Homocysteine is shown to be the thiol compound with the most potent inhibitory activity on matrix metalloproteinase 9. Zymographies reveal that matrix metalloproteinase 2 is, at least, as sensitive to inhibition by homocysteine as matrix metalloproteinase 9 is. This study opens new ways to the potential pharmacological use of thiol compounds.

Culture Media, Conditioned↗