Monoterpenes such as limonene and perillyl alcohol (POH) are promising natural compounds with pro-oxidant properties partly due to endoplasmic reticulum (ER) stress-induced cytotoxicity, and antioxidant activity owing to their activity as free radical scavengers, inhibition of coenzyme Q synthesis, activation of antioxidant-responsive elements (inducing detoxification enzymes) and induction of apoptosis. Activation of ER-stress responses generates reactive oxygen species (ROS), which are highly reactive free radicals mainly produced during mitochondrial electron transfer for adenosine triphosphate (ATP) synthesis. When cells are subjected to oxidative stress conditions, there is an accumulation of ROS that can lead to irreversible cell injury caused primarily by lipid peroxidation, protein aggregation and/or DNA damage. Malignant tumors, such as glioblastoma multiforme, display elevated rates of oxygen consumption, necrosis and abnormal structural microvasculature. Alterations in the tumor microenvironment are tightly linked to tumor progression and occur as a result of activation of complex signaling networks involving inter-clonal cooperation, cell-matrix interactions and an ongoing inflammatory response leading to genetic and epigenetic alterations. This review will focus on the pro- and anti-oxidant activities of POH, which are greatly dependent on the respective ROS levels within the tumor microenvironment and involve the ER stress response system. As well, some critical aspects of tumor-associated metabolic changes and the consequences of endogenous ROS production for tumor progression will be discussed.

This study evaluated the effects of a saxitoxin-producer strain (T3) of the cyanobacteria species Cylindrospermopsis raciborskii on the swimming movements of three cladoceran species (Daphnia gessneri, D. pulex, and Moina micrura). Acute toxicity bioassays were designed to access the effects of T3 strain, of a nonsaxitoxin producer strain (NPLP-1) of the same species and of a raw water sample from Funil reservoir (Rio de Janeiro, Brazil), that contained this and other cyanobacteria. In the acute bioassays, animals were exposed to C. raciborskii filaments or Funil water for 24-48 h and then transferred to food suspensions without cyanobacterial filaments for a further 48 h. During the exposure time to T3 strain filaments there was a decrease in the number of swimming individuals, with animals showing progressive immobilization. The same effect was observed with Funil water sample. Animals stayed alive on the bottom of the test tube and recovered swimming movements when transferred to food suspensions without toxic cells. This effect was not observed with the strain NPLP-1. The cladoceran D. pulex showed to be extremely sensitive to T3 strain and to Funil water containing C. raciborskii filaments, showing complete paralysis after 24-h exposure to T3 cell densities of 10(3) and 10(4) cells mL(-1), and after 24-h exposure to only 10% of raw water. However, D. gessneri was not sensitive to both T3 and to Funil water, whereas M. micrura was intermediate in sensitivity. This is the first report on the effects of cyanobacterial saxitoxins on movements of freshwater cladocerans, showing also difference in sensitivity among closely related Daphnia species.

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Among the epistemological obstacles described by Gaston Bachelard, we contend that unitary and pragmatic knowledge is correlated to the teleological categories of Ernst Mayr and is the basis for prevailing debate on the notion of "function" in biology. Given the proximity of the aspects highlighted by these authors, we propose to associate the role of teleological thinking in biology and the notion of unitary and pragmatic knowledge as an obstacle to scientific knowledge. Thus, teleological thinking persists acting as an epistemological obstacle in biology, according to Bachelardian terminology. Our investigation led us to formulate the "teleological obstacle," which we consider important for the future of biology and possibly other sciences. Palavras-chave: Gaston Bachelard (1884-1962 obstáculos epistemológicos; Ernst Mayr (1904-2005

Eugenia punicifolia known as "pedra-ume caá" is a shrub largely distributed in the Amazon region popularly used in decoctions or infusions as a natural therapeutic agent, which can interfere on cholinergic nicotinic neurotransmission. This work aimed to investigate a putative anti-inflammatory effect of dichloromethane fraction of E. punicifolia extract (Ep-CM) in the muscular lesion of mdx dystrophic mice, considering that activation of cholinergic mechanisms mitigates inflammation. A polymer containing the Ep-CM was implanted in mdx gastrocnemius muscle before onset of myonecrosis for local slow and gradual release of bioactive compounds and mice sacrificed 7 days or 9 weeks after surgery. Comparing to control muscle, treatment did not alter choline acetyltransferase and acetylcholinesterase enzymatic activities, but decreased metaloproteases-9 and -2 activities and levels of tumor necrosis factor α and NFκB transcription factor. In addition, treatment also reduced levels of bioactive IL-1β form and cleaved caspase-3, related to early events of cellular death and inflammatory activation and further increased myogenin expression without affecting collagen production which is associated with fibrosis. In vivo treatment of mdx dystrophic mice with Ep-CM caused significant reduction of muscular inflammation and improved skeletal muscle regeneration without inducing fibrosis.