Acidic pH derived from cancer cells may induce failed reprogramming of normal differentiated cells adjacent tumor cells and turn them into cancer cells

Background: Eelier studies demonstrated the up-regulation of some transcriptional factors such as Oct4, Nanog, Sox2 in undifferentiated cancer cells. These transcriptional regulators are up-regulated in pluripotent cells, as well and are responsible for cell reprogramming in normal cells. It might be said that normal cells adjacent tumor site are undergone of failed cell reprogramming. Presentation of the hypothesis: Extracellular pH of cancer cell is acidic and recent studies reveal the role of acidic environment in cell reprogramming of normal cells. This hypothesis deals with the potential role of acidic pH in malignant tumor development through normal cells adjacent cancer cells. It seems that cancer cells are more intelligent and acid release from these cells is not just a by-product but also and more important reason, is a tool to up-regulate cell reprogramming markers, induce epigenetic modification and tumor progress in normal cells adjacent cancer cells. If this is correct, then it could be expected that with alkaline targeting of tumor environment, failed cell reprogramming, aberrant epigenetic modification will decrease in normal cells adjacent cancer cells and afterward metastasis will decrease. Testing the hypothesis: It is proposed to investigate altered genetic and epigenetic modification (DNA methylation, histone modification) in cancer, early cancer and cells in vicinity of cancer cells at different pH range of 5.8-7.8. This study is performed to determine whether acidic pH induces reprogramming, global hypomethylation and promoter hypermethylation in cancer cells and cells in vicinity of cancer cells at different pH values. Implications of the hypothesis: This hypothesis deal with the ability of acidic pH to convert normal cells adjacent cancer cells to cancerous cells and its inductive potential on genetic and epigenetic modification of normal cells adjacent cancer cells and will further emphasize the important of extracellular acidic targeting in cancer therapy. © 2014 Elsevier Ltd

Erratum to: Mechano-Transduction Signals Derived from Self-Assembling Peptide Nanofibers Containing Long Motif of Laminin Influence Neurogenesis in In-Vitro and In-Vivo (Mol Neurobiol, 10.1007/s12035-016-9836-z)

Astroglial scaring and limited neurogenesis are two problematic issues in recovery of spinal cord injury (SCI). In the meantime, it seems that mechanical manipulations of scaffold to inhibit astroglial scarring and improve neurogenesis is worthy of value. In the present investigation, the effect of nanofiber (gel) concentration as a mechanical-stimuli in neurogenesis was investigated. Cell viability, membrane damage, and neural differentiation derived from endometrial stem cells encapsulated into self-assembling peptide nanofiber containing long motif of laminin were assessed. Then, two of their concentrations that had no significant difference of neural differentiation potential were selected for motor neuron investigation in SCI model of rat. MTT assay data showed that nanofibers at the concentrations of 0.125 and 0.25 % w/v induced higher and less cell viability than others, respectively, while cell viability derived from higher concentrations of 0.25 % w/v had ascending trend. Gene expression results showed that noggin along with laminin motif over-expressed TH gene and the absence of noggin or laminin motif did not in all concentrations. Bcl2 over-expression is concomitant with the decrease of nanofiber stiffness, NF+ cells increment, and astrogenesis inhibition and dark neuron decrement in SCI model. It seems that stiffness affects on Bcl2 gene expression and may through β-Catenin/Wnt signaling pathway and BMP-4 inhibition decreases astrogenesis and improves neurogenesis. However, stiffness had a significant effect on upregulation of GFAP+ cells and motor neuron recovery in in vivo. It might be concluded that eventually there is a critical definitive point concentration that at less or higher than of it changes cell behavior and neural differentiation through different molecular pathways

Angiotensin-converting enzyme inhibitors and cytokines in heart failure: dose and effect?∗∗Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.

Tyrosine hydroxylase (TH), a rate-limiting step in catecholamine synthesis in which its activity influences Alzheimer disease, Parkinson disease, and IQ of schizophrenia patients, has been studied for a long time. In the meantime, the present investigation assessed the effect of noggin and type of self-assembling nanofibers in TH gene over-expression by neuron-like cells derived from human endometrial-derived stromal cells (hEnSCs). Neuroblastoma cells and hEnSCs encapsulated into nanofibers including Matrigel, (RADA)4, laminin, and BMHP-1 motif bounded to (RADA)4 and their cell viability were studied for 48 h and 18 days in basal and neurogenic media, respectively, in noggin-rich media. Then, expression of neural genes and proteins has been investigated by immunocytochemistry (ICC) and real-time PCR methods, respectively. The results indicated that neuroblastoma cell and hEnSC viability is in good agreement with the level of Bcl2 and β-tubulin III gene expression; however, -BMHP-1 and -laminin nanofibers exhibited significantly higher cell viability eventually through Wnt/β-catenin signaling pathway as compared to others, respectively. The gene expression analysis of nanofibers showed that none of them induced gamma-aminobutyric acid (GABA) gene expression while glial fibrillary acidic protein (GFAP) gene just over-expressed in cells encapsulated into Matrigel with a low level of Bcl2 gene expression. However, the TH gene just had been over-expressed in cells encapsulated into -laminin nanofiber and 2D cell culture. In the absence of noggin with -laminin nanofibers, TH gene expression was suppressed. It might be concluded that although noggin through anti-BMP pathways resulted in GFAP decrement and TH gene increment, the type of scaffold that defined the final fate of cells and -laminin accompaniment might be useful for the recovery of Alzheimer and Parkinson disease patients. © 2016 Springer Science+Business Media New Yor

Density perturbations in f(R) gravity theories in metric and Palatini formalisms

We make a detailed study of matter density perturbations in both metric and Palatini formalisms in theories whose Lagrangian density is a general function, f(R), of the Ricci scalar. We derive these equations in a number of gauges. We show that for viable models that satisfy cosmological and local gravity constraints (LGC), matter perturbation equations derived under a sub-horizon approximation are valid even for super-Hubble scales provided the oscillating mode (scalaron) does not dominate over the matter-induced mode. Such approximate equations are especially reliable in the Palatini formalism because of the absence of scalarons. Using these equations we make a comparative study of the behaviour of density perturbations as well as gravitational potentials for a number of classes of theories. In the metric formalism the parameter m=Rf_{,RR}/f_{,R} characterising the deviation from the Lambda CDM model is constrained to be very small during the matter era in order to ensure compatibility with LGC, but the models in which m grows to the order of 10^{-1} around the present epoch can be allowed. These models also suffer from an additional fine tuning due to the presence of scalaron modes which are absent in the Palatini case. In Palatini formalism LGC and background cosmological constraints provide only weak bounds on |m| by constraining it to be smaller than ~ 0.1. This is in contrast to matter density perturbations which, on galactic scales, place far more stringent constraints on the present deviation parameter m of the order of |m| < 10^{-5} - 10^{-4}. This is due to the peculiar evolution of matter perturbations in the Palatini case which exhibits a rapid growth or a damped oscillation depending on the sign of m.Comment: 36 pages including 8 figures. Accepted for publication in Physical Review

In--out intermittency in PDE and ODE models

We find concrete evidence for a recently discovered form of intermittency, referred to as in--out intermittency, in both PDE and ODE models of mean field dynamos. This type of intermittency (introduced in Ashwin et al 1999) occurs in systems with invariant submanifolds and, as opposed to on--off intermittency which can also occur in skew product systems, it requires an absence of skew product structure. By this we mean that the dynamics on the attractor intermittent to the invariant manifold cannot be expressed simply as the dynamics on the invariant subspace forcing the transverse dynamics; the transverse dynamics will alter that tangential to the invariant subspace when one is far enough away from the invariant manifold. Since general systems with invariant submanifolds are not likely to have skew product structure, this type of behaviour may be of physical relevance in a variety of dynamical settings. The models employed here to demonstrate in--out intermittency are axisymmetric mean--field dynamo models which are often used to study the observed large scale magnetic variability in the Sun and solar-type stars. The occurrence of this type of intermittency in such models may be of interest in understanding some aspects of such variabilities.Comment: To be published in Chaos, June 2001, also available at http://www.eurico.web.co

Light Sheets and the Covariant Entropy Conjecture

We examine the holography bound suggested by Bousso in his covariant entropy conjecture, and argue that it is violated because his notion of light sheet is too generous. We suggest its replacement by a weaker bound.Comment: 5 pages, to appear in Classical and Quantum Gravit

The impact of the particle size of curcumin nanocarriers and the ethanol on beta1-integrin overexpression in fibroblasts: A regenerative pharmaceutical approach in skin repair and anti-aging formulations

Background: Since women pay more attention to their skin�s health, pharmaceutical companies invest heavily on skin care product development. Further, the success of drug nano-carriers in passing through the skin justifies the need to conduct studies at the nano-scale. β1-integrin down regulation has been proposed as a sign of skin aging. Methods: Six drug nano-carriers (50 and 75 nm) were prepared at three ethanol concentrations (0, 3,and 5) and different temperatures. Then, the impact of Nanocarriers on fibroblasts were investigated. Results: DLS showed that increasing ethanol concentration decreased the surface tension that caused a decrease in the particle size in non-temperature formulations while increasing the temperature to 60 °C to lower Gibbs free energy increased the particle size. Ethanol addition decreased β1-integrin over-expression, whereas larger nano-carriers induced an over-expression of β1-integrin, Bcl2/Bax ratio, and an increase in live cell number. β1-integrin over-expression did not correlate with the rate of fibroblast proliferation and NFκB expression. An increase in fibroblast mortality in relation to smaller nano-carriers was not only due to the increase in Bax ratio, but was related to NFκB over-expression. Conclusion: The development of a regenerative pharmaceutical approach in skin repair was based on the effect of particle size and ethanol concentration of the drug nano-carriers on the expression of β1-integrin in fibroblasts. A curcumin nanoformulation sized 77 nm and containing of 3 ethanol was more effective in increasing β1-integrin gene over-expression, anti-apoptosis of fibroblast cells (Bcl2/Bax ratio), and in decreasing Bax and NFκB gene expression than that with a particle size of 50 nm. Such a formulation may be considered a valuable candidate in anti-aging and wound-healing formulations. Figure not available: see fulltext.. © 2019, Springer Nature Switzerland AG

Second Order Perturbations of Flat Dust FLRW Universes with a Cosmological Constant

We summarize recent results concerning the evolution of second order perturbations in flat dust irrotational FLRW models with $\Lambda\ne 0$. We show that asymptotically these perturbations tend to constants in time, in agreement with the cosmic no-hair conjecture. We solve numerically the second order scalar perturbation equation, and very briefly discuss its all time behaviour and some possible implications for the structure formation.Comment: 6 pages, 1 figure. to be published in "Proceedings of the 5th Alexander Friedmann Seminar on Gravitation and Cosmology", Int. Journ. Mod. Phys. A (2002). Macros: ws-ijmpa.cls, ws-p9-75x6-50.cl