CAM and Cell Fate Targeting: Molecular and Energetic Insights into Cell Growth and Differentiation

Evidence-based medicine is switching from the analysis of single diseases at a time toward an integrated assessment of a diseased person. Complementary and alternative medicine (CAM) offers multiple holistic approaches, including osteopathy, homeopathy, chiropractic, acupuncture, herbal and energy medicine and meditation, all potentially impacting on major human diseases. It is now becoming evident that acupuncture can modify the expression of different endorphin genes and the expression of genes encoding for crucial transcription factors in cellular homeostasis. Extremely low frequency magnetic fields have been found to prime the commitment to a myocardial lineage in mouse embryonic stem cells, suggesting that magnetic energy may direct stem cell differentiation into specific cellular phenotypes without the aid of gene transfer technologies. This finding may pave the way to novel approaches in tissue engineering and regeneration. Different ginseng extracts have been shown to modulate growth and differentiation in pluripotent cells and to exert wound-healing and antitumor effects through opposing activities on the vascular system, prompting the hypothesis that ancient compounds may be the target for new logics in cell therapy. These observations and the subtle entanglement among different CAM systems suggest that CAM modalities may deeply affect both the signaling and transcriptional level of cellular homeostasis. Such a perception holds promises for a new era in CAM, prompting reproducible documentation of biological responses to CAM-related strategies and compounds. To this end, functional genomics and proteomics and the comprehension of the cell signaling networks may substantially contribute to the development of a molecular evidence–based CAM

Transcultural Perspective on Consciousness: A Bridge Between Anthropology, Medicine and Physics

  The Unesco Chair "Anthropology of Health, biosphere and Healing System" inside the University of Genoa (IT) is a unique experience inside the University of Genoa that stems from a cultural necessity to fill and a wealth of knowledge to preserve health, environment and treatment strategies considered strictly connected in modern medicine. This new, integrated approach contradicts and overcomes the traditional separation between humanities and scientific medicine and treatments. Health and approach to treatment strategies are not uniform around the worlds; the universal baseline is quality assurance of investigation in science The need to establish connections between Medicine, especially in the therapeutic aspect (healing), and all the information already obtained from the mind-matter phenomenology has led to much experimentation and theorizing in this border and transcultural area. The research group formed by anthropologist who have studied altered states of consciousness in different cultures, medical doctors, quantum physicists and molecular biologists will try to define a transcultural perspective on consciousness merging anthropology, medicine and physics.  In particular, the research field site is located in Mayantuyacu, a traditional healing center located in the Peruvian Amazon where the ancient art of ashanika healing is set. Mayantuyacu is situated on the bank of a river with thermal water at 100 ° flowing in the middle of the forest. Around the central Maloca, where is the common life, were built to accommodate malocas other people who come to Mayantuyacu to know and to seek treatment from knowing millennial ashanika and properties of thousands of plants including plants teacher. The following elements were firstly analyzed and considered the bridge from a traditional healing system to a new paradigm in medicine:                1. music called icaros,                2. master plants like ayahuasca involved during the healing ceremonies

Opioid Peptide Gene Expression in the Primary Hereditary Cardiomyopathy of the Syrian Hamster III. AUTOCRINE STIMULATION OF PRODYNORPHIN GENE EXPRESSION BY DYNORPHIN B

Prodynorphin mRNA and dynorphin B expression have been previously shown to be greatly increased in cardiac myocytes of BIO 14.6 cardiomyopathic hamsters. Here we report that exogenous dynorphin B induced a dose-dependent increase in prodynorphin mRNA levels and stimulated prodynorphin gene transcription in normal hamster myocytes. Similar responses were elicited by the synthetic selective kappa opioid receptor agonist U-50,488H. These effects were counteracted by the kappa opioid receptor antagonist Mr-1452 and were not observed in the presence of chelerythrine or calphostin C, two specific protein kinase C (PKC) inhibitors. Treatment of cardiomyopathic cells with Mr-1452 significantly decreased both prodynorphin mRNA levels and prodynorphin gene transcription. In control myocytes, dynorphin B induced the translocation of PKC-alpha to the nucleus and increased nuclear PKC activity without affecting the expression of PKC-delta, -epsilon, or -zeta. Acute release of either U-50,488H or dyn B over single normal or cardiomyopathic cells transiently increased the cytosolic Ca2+ concentration. A sustained treatment with each opioid agonist increased the cytosolic Ca2+ level for a more prolonged period in cardiomyopathic than in control myocytes and led to a depletion of Ca2+ from the sarcoplasmic reticulum in both groups of cells. The possibility that prodynorphin gene expression may affect the function of the cardiomyopathic cell through an autocrine mechanism is discussed

Opioid Peptide Gene Expression in the Primary Hereditary Cardiomyopathy of the Syrian Hamster II. ROLE OF INTRACELLULAR CALCIUM LOADING

We have previously shown that prodynorphin gene expression was markedly increased in adult myocytes of BIO 14.6 cardiomyopathic hamsters and that nuclear protein kinase C (PKC) may be involved in the induction of this opioid gene. Here we report that the cytosolic Ca2 xv v, b+ concentration was significantly increased in resting and in KCl-depolarized cardiomyopathic myocytes compared with normal cells. In normal and in cardiomyopathic cells, KCl significantly increased prodynorphin mRNA levels and prodynorphin gene transcription. These effects were abolished by the Ca2+ channel blocker verapamil. In control myocytes, the KCl-induced increase in prodynorphin mRNA expression was in part attenuated by chelerythrine or calphostin C, two selective PKC inhibitors. In these cells, KCl induced the translocation of PKC-α into the nucleus, increasing nuclear PKC activity. In resting cardiomyopathic myocytes, the increase in prodynorphin mRNA levels and gene transcription were significantly attenuated by the intracellular Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetraacetoxy-methylester being completely abolished when the chelating agent was administered in the presence of PKC inhibitors. KCl and the PKC activator 1,2-dioctanoyl-sn-glycerol additively stimulated prodynorphin gene expression both in normal and in cardiomyopathic cells. Therefore, we conclude that PKC activation and intracellular Ca2+ overload may represent the two major signaling mechanisms involved in the induction of the prodynorphin gene in cardiomyopathic cells

The Tick Formulation for deadlock detection and avoidance in railways traffic control

Wrong dispatching decisions may lead to deadlocks, where trains reciprocally block resources necessary to reach their destinations. It is crucial to develop tools to detect such potential deadlocks on time, in order to reverse the decisions previously taken by dispatchers or to take recovery actions. In this paper we present a new 0,1 linear formulation for detecting deadlocks and optimally park the involved trains to reduce congestion around the affected area. We discuss computational results on some realistic randomly generated instances to show the validity of the approach, as well as its limits.acceptedVersio

Easy Cases of Deadlock Detection in Train Scheduling

A deadlock occurs when two or more trains are preventing each other from moving forward by occupying the required tracks. Deadlocks are rare but pernicious events in railroad operations and, in most cases, are caused by human errors. Recovering is a time-consuming and costly operation, producing large delays and often requiring crew rescheduling and complex switching moves. In practice, most deadlocks involve only two long trains missing their last potential meet location. In this paper, we prove that, for any network configuration, the identification of two-train deadlocks can be performed in polynomial time. This is the first exact polynomial algorithm for such a practically relevant combinatorial problem. We also develop a pseudo-polynomial but efficient oracle that allows real-time early detection and prevention of any (potential) two-train deadlock in the Union Pacific (a U.S. class 1 rail company) railroad network. A deadlock prevention module based on the work in this paper will be put in place at Union Pacific to prevent all deadlocks of this kind.acceptedVersio

Unveiling the morphogenetic code: A new path at the intersection of physical energies and chemical signaling

In this editorial, we discuss the remarkable role of physical energies in the control of cell signaling networks and in the specification of the architectural plan of both somatic and stem cells. In particular, we focus on the biological relevance of bioelectricity in the pattern control that orchestrates both developmental and regenerative pathways. To this end, the narrative starts from the dawn of the first studies on animal electricity, reconsidering the pioneer work of Harold Saxton Burr in the light of the current achievements. We finally discuss the most recent evidence showing that bioelectric signaling is an essential component of the informational processes that control pattern specification during embryogenesis, regeneration, or even malignant transformation. We conclude that there is now mounting evidence for the existence of a Morphogenetic Code, and that deciphering this code may lead to unprecedented opportunities for the development of novel paradigms of cure in regenerative and precision medicine

Management of Obesity and Obesity-Related Disorders: From Stem Cells and Epigenetics to Its Treatment

: Obesity is a complex worldwide disease, characterized by an abnormal or excessive fat accumulation. The onset of this pathology is generally linked to a complex network of interactions among genetic and environmental factors, aging, lifestyle, and diets. During adipogenesis, several regulatory mechanisms and transcription factors are involved. As fat cells grow, adipose tissue becomes increasingly large and dysfunctional, losing its endocrine function, secreting pro-inflammatory cytokines, and recruiting infiltrating macrophages. This long-term low-grade systemic inflammation results in insulin resistance in peripheral tissues. In this review we describe the main mechanisms involved in adipogenesis, from a physiological condition to obesity. Current therapeutic strategies for the management of obesity and the related metabolic syndrome are also reported

Dynorphin gene expression and release in the myocardial cell.

The expression of the prodynorphin gene was investigated in adult cultured rat ventricular cardiac myocytes by using a sensitive solution hybridization RNase protection assay for the quantitative analysis of prodynorphin mRNA. Myocyte culture in high KCl resulted, after 4 h, in a marked increase in cellular prodynorphin mRNA, while a KCl treatment for 6, 12, or 24 h progressively down-regulated the levels of prodynorphin mRNA below the control value. Immunoreactive dynorphin B, a biologically active end product of the precursor, was found to be present in the culture medium in significantly higher amounts than in the cardiac myocytes. The levels of this biologically active K opioid receptor agonist significantly increased after 4 h of KCl treatment and were markedly reduced following a 24-h exposure of the cardiac myocytes to KCl. These KCl-induced effects were all abolished by cell incubation in the presence of the calcium channel blocker verapamil. In single cardiac myocytes, acute stimulation of K opioid receptors with dynorphin B or with the selective agonist U-50,488H increased the level of cytosolic calcium. This effect was abolished by the specific K opioid receptor antagonist (Mr-1452) and was not affected by the removal of calcium from the bathing medium. These results suggest that an opioid gene may influence the myocardial function in an autocrine or paracrine fashion