This week’s selection of recently published papers from MDPI journals.
Cancer Stem Cell Theory and the Warburg Effect, Two Sides of the Same Coin?
Abstract: Over the last 100 years, many studies have been performed to determine the biochemical and histopathological phenomena that mark the origin of neoplasms. At the end of the last century, the leading paradigm, which is currently well rooted, considered the origin of neoplasms to be a set of genetic and/or epigenetic mutations, stochastic and independent in a single cell, or rather, a stochastic monoclonal pattern. However, in the last 20 years, two important areas of research have underlined numerous limitations and incongruities of this pattern, the hypothesis of the so-called cancer stem cell theory and a revaluation of several alterations in metabolic networks that are typical of the neoplastic cell, the so-called Warburg effect. Even if this specific “metabolic sign” has been known for more than 85 years, only in the last few years has it been given more attention; therefore, the so-called Warburg hypothesis has been used in multiple and independent surveys. Based on an accurate analysis of a series of considerations and of biophysical thermodynamic events in the literature, we will demonstrate a homogeneous pattern of the cancer stem cell theory, of the Warburg hypothesis and of the stochastic monoclonal pattern; this pattern could contribute considerably as the first basis of the development of a new uniform theory on the origin of neoplasms. Thus, a new possible epistemological paradigm is represented; this paradigm considers the Warburg effect as a specific “metabolic sign” reflecting the stem origin of the neoplastic cell, where, in this specific metabolic order, an essential reason for the genetic instability that is intrinsic to the neoplastic cell is defined.
For Open Access Article, see: Pacini, N.; Borziani, F. Cancer Stem Cell Theory and the Warburg Effect, Two Sides of the Same Coin? Int. J. Mol. Sci. 2014, 15, 8893-8930.
Over-Expression of Catalase in Myeloid Cells Confers Acute Protection Following Myocardial Infarction
Abstract: Cardiovascular disease is the leading cause of death in the United States and new treatment options are greatly needed. Oxidative stress is increased following myocardial infarction and levels of antioxidants decrease, causing imbalance that leads to dysfunction. Therapy involving catalase, the endogenous scavenger of hydrogen peroxide (H2O2), has been met with mixed results. When over-expressed in cardiomyocytes from birth, catalase improves function following injury. When expressed in the same cells in an inducible manner, catalase showed a time-dependent response with no acute benefit, but a chronic benefit due to altered remodeling. In myeloid cells, catalase over-expression reduced angiogenesis during hindlimb ischemia and prevented monocyte migration. In the present study, due to the large inflammatory response following infarction, we examined myeloid-specific catalase over-expression on post-infarct healing. We found a significant increase in catalase levels following infarction that led to a decrease in H2O2 levels, leading to improved acute function. This increase in function could be attributed to reduced infarct size and improved angiogenesis. Despite these initial improvements, there was no improvement in chronic function, likely due to increased fibrosis. These data combined with what has been previously shown underscore the need for temporal, cell-specific catalase delivery as a potential therapeutic option.
For Open Access Article, see: Cabigas, E.B.; Somasuntharam, I.; Brown, M.E.; Che, P.L.; Pendergrass, K.D.; Chiang, B.; Taylor, W.R.; Davis, M.E. Over-Expression of Catalase in Myeloid Cells Confers Acute Protection Following Myocardial Infarction. Int. J. Mol. Sci. 2014, 15, 9036-9050.
On the Isomorphism between Dissipative Systems, Fractal Self-Similarity and Electrodynamics. Toward an Integrated Vision of Nature
Abstract: In electrodynamics there is a mutual exchange of energy and momentum between the matter field and the electromagnetic field and the total energy and momentum are conserved. For a constant magnetic field and harmonic scalar potential, electrodynamics is shown to be isomorph to a system of damped/amplified harmonic oscillators. These can be described by squeezed coherent states which in turn are isomorph to self-similar fractal structures. Under the said conditions of constant magnetic field and harmonic scalar potential, electrodynamics is thus isomorph to fractal self-similar structures and squeezed coherent states. At a quantum level, dissipation induces noncommutative geometry with the squeezing parameter playing a relevant role. Ubiquity of fractals in Nature and relevance of coherent states and electromagnetic interaction point to a unified, integrated vision of Nature.
For Open Access Article, see: Vitiello, G. On the Isomorphism between Dissipative Systems, Fractal Self-Similarity and Electrodynamics. Toward an Integrated Vision of Nature. Systems 2014, 2, 203-216.
Updates and Controversies in the Rapidly Evolving Field of Lung Cancer Screening, Early Detection, and Chemoprevention
Abstract: Lung cancer remains the leading cause of cancer-related death in the United States. Cigarette smoking is a well-recognized risk factor for lung cancer, and a sustained elevation of lung cancer risk persists even after smoking cessation. Despite identifiable risk factors, there has been minimal improvement in mortality for patients with lung cancer primarily stemming from diagnosis at a late stage when there are few effective therapeutic options. Early detection of lung cancer and effective screening of high-risk individuals may help improve lung cancer mortality. While low dose computerized tomography (LDCT) screening of high risk smokers has been shown to reduce lung cancer mortality, the high rates of false positives and potential for over-diagnosis have raised questions on how to best implement lung cancer screening. The rapidly evolving field of lung cancer screening and early-detection biomarkers may ultimately improve the ability to diagnose lung cancer in its early stages, identify smokers at highest-risk for this disease, and target chemoprevention strategies. This review aims to provide an overview of the opportunities and challenges related to lung cancer screening, the field of biomarker development for early lung cancer detection, and the future of lung cancer chemoprevention.
For Open Access Article, see: Kathuria, H.; Gesthalter, Y.; Spira, A.; Brody, J.S.; Steiling, K. Updates and Controversies in the Rapidly Evolving Field of Lung Cancer Screening, Early Detection, and Chemoprevention. Cancers 2014, 6, 1157-1179.
Colonization and Infection of the Skin by S. aureus: Immune System Evasion and the Response to Cationic Antimicrobial Peptides
Abstract: Staphylococcus aureus (S. aureus) is a widespread cutaneous pathogen responsible for the great majority of bacterial skin infections in humans. The incidence of skin infections by S. aureus reflects in part the competition between host cutaneous immune defenses and S. aureusvirulence factors. As part of the innate immune system in the skin, cationic antimicrobial peptides (CAMPs) such as the β-defensins and cathelicidin contribute to host cutaneous defense, which prevents harmful microorganisms, like S. aureus, from crossing epithelial barriers. Conversely, S. aureus utilizes evasive mechanisms against host defenses to promote its colonization and infection of the skin. In this review, we focus on host-pathogen interactions during colonization and infection of the skin by S. aureus and methicillin-resistant Staphylococcus aureus (MRSA). We will discuss the peptides (defensins, cathelicidins, RNase7, dermcidin) and other mediators (toll-like receptor, IL-1 and IL-17) that comprise the host defense against S. aureus skin infection, as well as the various mechanisms by which S. aureus evades host defenses. It is anticipated that greater understanding of these mechanisms will enable development of more sustainable antimicrobial compounds and new therapeutic approaches to the treatment of S. aureus skin infection and colonization.
For Open Access Article, see: Ryu, S.; Song, P.I.; Seo, C.H.; Cheong, H.; Park, Y. Colonization and Infection of the Skin by S. aureus: Immune System Evasion and the Response to Cationic Antimicrobial Peptides. Int. J. Mol. Sci. 2014, 15, 8753-8772.