Cell Cycle Inhibition without Disruption of Neurogenesis Is a Strategy for Treatment of Aberrant Cell Cycle Diseases: An Update

Since publishing our earlier report describing a strategy for the treatment of central nervous system (CNS) diseases by inhibiting the cell cycle and without disrupting neurogenesis (Liu et al. 2010), we now update and extend this strategy to applications in the treatment of cancers as well. Here, we put forth the concept of “aberrant cell cycle diseases” to include both cancer and CNS diseases, the two unrelated disease types on the surface, by focusing on a common mechanism in each aberrant cell cycle reentry. In this paper, we also summarize the pharmacological approaches that interfere with classical cell cycle molecules and mitogenic pathways to block the cell cycle of tumor cells (in treatment of cancer) as well as to block the cell cycle of neurons (in treatment of CNS diseases). Since cell cycle inhibition can also block proliferation of neural progenitor cells (NPCs) and thus impair brain neurogenesis leading to cognitive deficits, we propose that future strategies aimed at cell cycle inhibition in treatment of aberrant cell cycle diseases (i.e., cancers or CNS diseases) should be designed with consideration of the important side effects on normal neurogenesis and cognition

Elevating microRNA-122 in blood improves outcomes after temporary middle cerebral artery occlusion in rats.

Because our recent studies have demonstrated that miR-122 decreased in whole blood of patients and in whole blood of rats following ischemic stroke, we tested whether elevating blood miR-122 would improve stroke outcomes in rats. Young adult rats were subjected to a temporary middle cerebral artery occlusion (MCAO) or sham operation. A polyethylene glycol-liposome-based transfection system was used to administer a miR-122 mimic after MCAO. Neurological deficits, brain infarction, brain vessel integrity, adhesion molecule expression and expression of miR-122 target and indirect-target genes were examined in blood at 24 h after MCAO with or without miR-122 treatment. miR-122 decreased in blood after MCAO, whereas miR-122 mimic elevated miR-122 in blood 24 h after MCAO. Intravenous but not intracerebroventricular injection of miR-122 mimic decreased neurological deficits and brain infarction, attenuated ICAM-1 expression, and maintained vessel integrity after MCAO. The miR-122 mimic also down-regulated direct target genes (e.g. Vcam1, Nos2, Pla2g2a) and indirect target genes (e.g. Alox5, Itga2b, Timp3, Il1b, Il2, Mmp8) in blood after MCAO which are predicted to affect cell adhesion, diapedesis, leukocyte extravasation, eicosanoid and atherosclerosis signaling. The data show that elevating miR-122 improves stroke outcomes and we postulate this occurs via downregulating miR-122 target genes in blood leukocytes

Vortex generation in stirred binary Bose-Einstein condensates

The dynamical vortex production, with a trap-confining time-dependent stirred potential, is studied by using mass-imbalanced cold-atom coupled Bose-Einstein condensates (BEC). The vortex formation is explored by considering that both coupled species are confined by a pancake-like harmonic trap, slightly modified elliptically by a time-dependent periodic potential, with the characteristic frequency enough larger than the transversal trap frequency. The approach is applied to the experimentally accessible binary mixtures $^{85}$Rb-$^{133}$Cs and $^{85}$Rb-$^{87}$Rb, which allow us to verify the effect of mass differences in the dynamics. For both species, the time evolutions of the respective energy contributions, together with associated velocities, are studied in order to distinguish turbulent from non-turbulent flows. By using the angular momentum and moment of inertia mean values, effective classical rotation frequencies are suggested, which are further considered within simulations in the rotating frame without the stirring potential. Spectral analysis is also provided for both species, with the main focus being the incompressible kinetic energies. In the transient turbulent regime, before stable vortex patterns are produced, the characteristic $k^{-5/3}$ Kolmogorov behavior is clearly identified for both species at intermediate momenta $k$ above the inverse Thomas-Fermi radial positions, further modified by the universal $k^{-3}$ scaling at momenta higher than the inverse of the respective healing lengths. Emerging from the mass-imbalanced comparison, relevant is to observe that, as larger is the mass difference, much faster is the dynamical production of stable vortices.Comment: 17 pages, 16 figure

Modelling and detecting tumour oxygenation levels.

Tumours that are low in oxygen (hypoxic) tend to be more aggressive and respond less well to treatment. Knowing the spatial distribution of oxygen within a tumour could therefore play an important role in treatment planning, enabling treatment to be targeted in such a way that higher doses of radiation are given to the more radioresistant tissue. Mapping the spatial distribution of oxygen in vivo is difficult. Radioactive tracers that are sensitive to different levels of oxygen are under development and in the early stages of clinical use. The concentration of these tracer chemicals can be detected via positron emission tomography resulting in a time dependent concentration profile known as a tissue activity curve (TAC). Pharmaco-kinetic models have then been used to deduce oxygen concentration from TACs. Some such models have included the fact that the spatial distribution of oxygen is often highly inhomogeneous and some have not. We show that the oxygen distribution has little impact on the form of a TAC; it is only the mean oxygen concentration that matters. This has significant consequences both in terms of the computational power needed, and in the amount of information that can be deduced from TACs

Low radiation dose to treat pneumonia and other inflammations

Infection, the invasion of pathogenic microorganisms and viruses, causes reactive inflammation mediated by endogenous signals, with influx of leucocytes with distinct properties and capable of mounting a cellular or antibody response. Different forms of inflammation may also occur in response to tumours, in allergy and autoimmune disorders. Pneumonia, respiratory tract infection and septic shock for instance can arise as serious complications of the Covid-19 virus. While radiotherapy has been most widely used to control malignant tumours, it has also been used for treatment of non-malignant diseases, including acute and chronic inflammation in situations where anti-inflammatory drugs may be ineffective or contraindicated. The present review examines the history and prospects for low-dose anti-inflammatory radiation treatments, the present interest largely being motivated by the increased incidence of pulmonary disease associated Covid-19 infections. Evidence in support of the suggested efficacy are covered, together with an appraisal of one of the number of potential convenient sources that could complement external beam arrangements

Dilution and magnification effects on image analysis applications in activated sludge characterization

The properties of activated sludge systems can be characterized using image analysis procedures. When these systems operate with high biomass content, accurate sludge characterization requires samples to be diluted. Selection of the best image acquisition magnification is directly related to the amount of biomass screened. The aim of the present study was to survey the effects of dilution and magnification on the assessment of aggregated and filamentous bacterial content and structure using image analysis procedures. Assessments of biomass content and structure were affected by dilutions. Therefore, the correct operating dilution requires careful consideration. Moreover, the acquisition methodology comprising a 100 magnification allowed data on aggregated and filamentous biomass to be determined and smaller aggregates to be identified and characterized, without affecting the accuracy of lower magnifications regarding biomass representativeness.AGERE (Empresa de Águas, Efluentes e Resíduos de Braga – EM) and AGS(Administração e Gestão de Sistemas de Salubridade, S.A.)Fundação para a Ciência e Tecnologia (FCT

Low dose ionising radiation-induced hormesis: Therapeutic implications to human health

The concept of radiation-induced hormesis, whereby a low dose is beneficial and a high dose is detrimental, has been gaining attention in the fields of molecular biology, environmental toxicology and radiation biology. There is a growing body of literature that recognises the importance of hormetic dose response not only in the radiation field, but also with molecular agents. However, there is continuing debate on the magnitude and mechanism of radiation hormetic dose response, which could make further contributions, as a research tool, to science and perhaps eventually to public health due to potential therapeutic benefits for society. The biological phenomena of low dose ionising radiation (LDIR) includes bystander effects, adaptive response, hypersensitivity, radioresistance and genomic instability. In this review, the beneficial and the detrimental effects of LDIR-induced hormesis are explored, together with an overview of its underlying cellular and molecular mechanisms that may potentially provide an insight to the therapeutic implications to human health in the future