Silencing of the MEG3 gene promoted anti-cancer activity and drug sensitivity in glioma

Aberrant expression of MEG3 has been shown in various cancers. The purpose of this study is to evaluate the effect of MEG3 on glioma cells and the use of potential chemotherapeutics in glioma by modulating MEG3 expression. Cell viability, migration and chemosensitivity were assayed. Cell death was evaluated in MEG3 overexpressing and MEG3 suppressed cells. MEG3 expression was compared in patient-derived glioma cells concerning IDH1 mutation and WHO grades. Silencing of MEG3 inhibited cell proliferation and reduced cell migration while overexpression of MEG3 promoted proliferation in glioma cells. MEG3 inhibition improved the chemosensitivity of glioma cells to 5-fluorouracil (5FU) but not to navitoclax. On the other hand, there is no significant effect of MEG3 expression on temozolamide (TMZ) treatment which is a standard chemotherapeutic agent in glioma. Suppression of the MEG3 gene in patient-derived oligodendroglioma cells also showed the same effect whereas glioblastoma cell proliferation and chemosensitivity were not affected by MEG3 inhibition. Further, as a possible cell death mechanism of action apoptosis was investigated. Although MEG3 is a widely known tumour suppressor gene and its loss is associated with several cancer types, here we reported that MEG3 inhibition can be used for improving the efficiency of known chemotherapeutic drug sensitivity. We propose that the level of MEG3 should be evaluated in the treatment of different glioma subtypes that are resistant to effective drugs to increase the potential effective drug applications.     

Aspects of the biology of the euryhaline Asian cichlid,Etroplus suratensis

Synopsis Aspects of the biology of the euryhaline Asian cichlid Etroplus suratensis in a coastal lagoon of Sri Lanka were studied for a period of 15 months. Comparisons are made from the catches from the fishery of manmade, inland freshwater reservoirs. Changes in the stock structure in the sublittoral region of the lagoon indicate that recruitment takes place twice a year, during the high rainfall/low salinity periods. The feeding habits of E. suratensis were different in the two habitats. In the lagoon it fed mainly on molluscs and in the freshwater reservoirs on macrophytes. Feeding chronology based on diurnal surveys indicate that it feeds mainly during the daylight hours. The dentition of E. suratensis is adapted for both tearing and crushing (pharyngeal teeth). Distinct differences in the mean relative intestinal length between populations from the coastal lagoon and inland reservoirs were evident and these differences are correlated to their respective feeding habits. Diurnal changes in feeding activity are associated with changes in the stomach pH. The egg-diameter distribution of mature fish indicate that E. suratensis is a single spawner, that it sheds its mature eggs all at once. It is inferred that E. suratensis breeds twice a year but that an individual female is capable of spawning only once a year.     

A and alpha supernatant pretreatment of Saccharomyces cerevisiae cells affects both the kinetics and efficiency of mating.

The effects of culture supernatant treatment on subsequent matings between pretreated a and alpha Saccharomyces cerevisiae cells were studied. For each experiment, pairs of a and alpha [rho+] or [rho- rho0] cells in the logarithmic growth phase in defined minimal medium were pretreated for a total of 15 min (by exchanging their cell-free supernatants or by mixing samples of a and alpha cell cultures) and then mated in defined minimal (YNB) or enriched (YEP) liquid medium. All pretreated cells, regardless of treatment procedure, initiated cell fusion 15 to 35 min faster than did their nontreated counterparts. In all cases, pretreated cells mated 8 to 20% more efficiently than did nonpretreated ones. Regardless of the strains, the hierarchy of mating efficiency was always treated YEP greater than untreated YEP greater than treated YNB greater than untreated YNB. The cell fusion kinetics in alpha [rho+] X a [rho-] crosses were most affected by pretreatment (delta 30 to 35 min), whereas [rho+] X [rho+] crosses were least affected (delta 15 min). These results are discussed in relation to the functions known for a and alpha pheromones. The successful pretreatment regimes were used to design new rapid and efficient techniques for mating YNB-grown log-phase cells in either YNB or YEP liquid media. These techniques can be used for small- or large-scale mating, and because of their inherent media flexibility, they have many potential applications to future studies on mating-specific or intrazygotic phenomena.     

Phytochemical profile and antioxidant activity of extracts of the peruvian peppertree Schinus areira L. from Chile

The Andean tree Schinus areira L. has multiple traditional uses, from the treatment of bronchitis and rheumatic diseases to menstrual cycle regulation and wound healing. With reported hypotensive, analgesic, antitumoral and anti-inflammatory properties, it acts predominantly against diseases related to oxidative stress. This study focuses on the antioxidant activity and phytochemical profile of the extracts of Schinus areira L.Serial extraction of the fruits was performed both by maceration and by Soxhlet. Total phenols and flavonoids were measured using the Folin-Ciocalteu method and AlCl₃, respectively. In vitro antioxidant activity was determined by FRAP and DPPH.Results were similar for both extraction methods. Primary metabolites detected included carbohydrates, proteins and amino acids; secondary metabolites included tannins, flavonoids, saponins, steroids and triterpenes. Antioxidant activity was confirmed for ethyl acetate, methanolic and aqueous extracts. The methanolic extract had both the highest polyphenol content (>195 mg GAE/ g dry weight) and the highest antioxidant activity [EC₅₀ > 476 μg/mL; >273 mg AA/g dry weight (DPPH); >301 mg AA/ g dry weight (FRAP)]. The extract does not produce macrophage cytotoxicity in RAW 264.7, which is indicated by an average cytotoxicity of 2% over 24 h.Our study serves as a starting point for future research on the pharmacological properties of Schinus areira L.     

2-Substituted-3H-indol-3-one-1-oxides: Preparation and Radical Trapping Properties

A series of 2-alkyl and 2-aryl substituted-3H-indol-3-one-1-oxides was prepared and evaluated for its radical trapping properties. Spin trapping and electron paramagnetic resonance experiments demonstrate the ability of these indolone-1-oxides to trap hetero- and carbon-centered radicals. The most stable spin adducts (lifetime of several hours) are obtained with 2-alkyl substituted nitrones, the 2-ethyl-5,6-dioxolo-3H-indolone-1-oxide, 5e and the 2-secbutyl-3H-indolone-1-oxide, 5f. These two nitrones are also sensitive to redox reactions in solution. Therefore this indolone-1-oxide series lacking a β-hydrogen atom gives rise to highly stable adducts with free radicals.     

Nucleolar organizer regions in Sittasomus griseicapillus and Lepidocolaptes angustirostris (Aves,Dendrocolaptidae): Evidence of a chromosome inversion

Cytogenetic studies in birds are still scarce compared to other vertebrates. Woodcreepers (Dendrocolaptidae) are part of a highly specialized group within the Suboscines of the New World. They are forest birds exclusive to the Neotropical region and similar to woodpeckers, at a comparable evolutionary stage. This paper describes for the first time the karyotypes of the Olivaceous and the Narrow-billed Woodcreeper using conventional staining with Giemsa and silver nitrate staining of the nucleolar organizer regions (Ag-NORs). Metaphases were obtained by fibular bone marrow culture. The chromosome number of the Olivaceous Woodcreeper was 2n = 82 and of the Narrow-billed Woodcreeper, 2n = 82. Ag-NORs in the largest macrochromosome pair and evidence of a chromosome inversion are described herein for the first time for this group.     

Stem Cell Transplantation in Traumatic Spinal Cord Injury: A Systematic Review and Meta-Analysis of Animal Studies

Spinal cord injury (SCI) is a devastating condition that causes substantial morbidity and mortality and for which no treatments are available. Stem cells offer some promise in the restoration of neurological function. We used systematic review, meta-analysis, and meta-regression to study the impact of stem cell biology and experimental design on motor and sensory outcomes following stem cell treatments in animal models of SCI. One hundred and fifty-six publications using 45 different stem cell preparations met our prespecified inclusion criteria. Only one publication used autologous stem cells. Overall, allogeneic stem cell treatment appears to improve both motor (effect size, 27.2%; 95% Confidence Interval [CI], 25.0%–29.4%; 312 comparisons in 5,628 animals) and sensory (effect size, 26.3%; 95% CI, 7.9%–44.7%; 23 comparisons in 473 animals) outcome. For sensory outcome, most heterogeneity between experiments was accounted for by facets of stem cell biology. Differentiation before implantation and intravenous route of delivery favoured better outcome. Stem cell implantation did not appear to improve sensory outcome in female animals and appeared to be enhanced by isoflurane anaesthesia. Biological plausibility was supported by the presence of a dose–response relationship. For motor outcome, facets of stem cell biology had little detectable effect. Instead most heterogeneity could be explained by the experimental modelling and the outcome measure used. The location of injury, method of injury induction, and presence of immunosuppression all had an impact. Reporting of measures to reduce bias was higher than has been seen in other neuroscience domains but were still suboptimal. Motor outcomes studies that did not report the blinded assessment of outcome gave inflated estimates of efficacy. Extensive recent preclinical literature suggests that stem-cell–based therapies may offer promise, however the impact of compromised internal validity and publication bias mean that efficacy is likely to be somewhat lower than reported here.     

Black Yeast Biota in the Mangrove, in Search of the Origin of the Lethargic Crab Disease (LCD)

Knowledge of natural ecology is essential for a better understanding of pathogenicity and opportunism in black yeast-like fungi. Although etiological agents of diseases caused by these fungi are supposed to originate from the environment, their isolation from nature is difficult. This is probably due to their oligotrophic nature, low competitive ability, and, overall, insufficient data on their natural habitat. We obtained environmental samples from mangrove areas where mortalities by lethargic crab disease (LCD) are reported and areas without disease recorded. Isolation of chaetothyrialean black yeasts and relatives was performed using a highly selective protocol. Species-specific primers were used to determine if these isolates represented Exophiala cancerae or Fonsecaea brasiliensis, two proven agents of LCD, in order to test hypotheses about the origin of the disease. Isolates, identified by morphology as Fonsecaea- or Exophiala-like, were tested specific diagnostic markers for the fungi associated with LCD. Although several black fungi were isolated, the main causative agent of the LCD, E. cancerae, was not found. Molecular markers for F. brasiliensis revealed 10 positive bands for isolates from biofilms on mangrove leaves, branches, and aerial roots, of which four were confirmed by ITS sequencing. The absence of E. cancerae in environmental samples suggests that the species is dependent on the crab, as a genuine pathogen, different from F. brasiliensis, which is probably not dependent on the host species, U. cordatus. However, we did not attempt isolation from the marine water, which may represent the pathway of dispersion of the black yeast species between neighbor mangroves.