Oncogenesis- kaleidoscopic and multi-level reality

Oncogenesis is an extremely complex phenomenon. The mechanisms by which cancer is induced is only partially known. Consequently, therapeutic targets may be uncertain and results are often unsatisfactory. The purpose of this paper is to develop a trans-level and multiple transdisciplinary perspective describing the kaleidoscopic reality of oncogenesis. This manner of understanding oncogenesis as a complex process characterized by a non-linear dynamic, far from equilibrium and with unpredictable evolution, transcends the classical perspective and requires a paradigm shift. This approach is also facilitated by recent studies that focus on group phenomena, with emerging behaviors in a continuous phase transition. Biological systems, and obviously the human organism, express this type of behavior with critical self-organizing valences in the context of a genome - mesotope (environment) - phenotype interaction. For example, nature has transposed in the ecosystem, among other things, the performance pattern of its mineral history represented by the dynamic energy-matter-information unit (the principle of invariance). And multi-cell biological systems in the phylogenetic tree crown have multiple directed aerobic metabolisms in accordance with specific functions. Cancers, in turn, have a hybrid (anaerobic and aerobic) and unidirectional metabolism whose only and ultimate reason is the survival of the malignant cell. Understanding the transdisciplinary reality of oncogenesis offers novel development paths for new therapeutic strategies compared to current ones which have relatively limited efficiency

TSPO: kaleidoscopic 18-kDa amid biochemical pharmacology, control and targeting of mitochondria

The 18-kDa translocator protein (TSPO) localizes in the outer mitochondrial membrane (OMM) of cells and is readily up-regulated under various pathological conditions such as cancer, inflammation, mechanical lesions and neurological diseases. Able to bind with high affinity synthetic and endogenous ligands, its core biochemical function resides in the translocation of cholesterol into the mitochondria influencing the subsequent steps of (neuro-)steroid synthesis and systemic endocrine regulation. Over the years, however, TSPO has also been linked to core cellular processes such as apoptosis and autophagy. It interacts and forms complexes with other mitochondrial proteins such as the voltage-dependent anion channel (VDAC) via which signalling and regulatory transduction of these core cellular events may be influenced. Despite nearly 40 years of study, the precise functional role of TSPO beyond cholesterol trafficking remains elusive even though the recent breakthroughs on its high-resolution crystal structure and contribution to quality-control signalling of mitochondria. All this along with a captivating pharmacological profile provides novel opportunities to investigate and understand the significance of this highly conserved protein as well as contribute the development of specific therapeutics as presented and discussed in the present review

Experimental investigation of the mechanical stiffness of periodic framework-patterned elastomers

Recent advances in the cataloguing of three-dimensional nets mean a systematic search for framework structures with specific properties is now feasible. Theoretical arguments about the elastic deformation of frameworks suggest characteristics of mechanically isotropic networks. We explore these concepts on both isotropic and anisotropic networks by manufacturing porous elastomers with three different periodic net geometries. The blocks of patterned elastomers are subjected to a range of mechanical tests to determine the dependence of elastic moduli on geometric and topological parameters. We report results from axial compression experiments, three-dimensional X-ray computed tomography imaging and image-based finite-element simulations of elastic properties of framework-patterned elastomers