Emerging cellular functions of the lipid metabolizing enzyme 15‐Lipoxygenase‐1

The oxygenation of polyunsaturated fatty acids such as arachidonic and linoleic acid through lipoxygenases (LOXs) and cyclooxygenases (COXs) leads to the production of bioactive lipids that are important both in the induction of acute inflammation and its resolution. Amongst the several isoforms of LOX that are expressed in mammals, 15‐LOX‐1 was shown to be important both in the context of inflammation, being expressed in cells of the immune system, and in epithelial cells where the enzyme has been shown to crosstalk with a number of important signalling pathways. This review looks into the latest developments in understanding the role of 15‐LOX‐1 in different disease states with emphasis on the emerging role of the enzyme in the tumour microenvironment as well as a newly re‐discovered form of cell death called ferroptosis. We also discuss future perspectives on the feasibility of use of this protein as a target for therapeutic interventions.     

Melanocortins and opioids modulate early postnatal growth in rats

This study was undertaken to investigate the effects of melanocortins and opioids on rat early postnatal body and organ growth. Among melanocortins tested desacetyl-alpha-melanocyte-stimulating hormone (alpha-MSH) at dosages of 0.3 and 3 micrograms/g/day was effective in stimulating neonatal growth with a weight gain of 7 and 5.6%, respectively, after 2 weeks of treatment. Likewise, a weight rise of 4.2 and 3% was obtained with 3 micrograms/g/day of both alpha-MSH and Nle4-D-Phe7 alpha-MSH. As far as opioids were concerned, while N-acetyl-beta-endorphin (beta-End) was ineffective, the activity of beta-End was dependent on dosage. Indeed, newborns treated with 0.03 microgram/g/day showed a slight, but significant, increase in weight, whereas a marked decrease in growth followed treatment with 0.3 and, mainly, 3 micrograms/g/day, with a final weight loss of 3.4 and 5.5%, respectively. All melanocortins exerted a positive action on muscular and brain trophism and, in addition, desacetyl-alpha-MSH also induced a rise of fat deposits. On the contrary, while the 0.03 microgram/g/day beta-End dose caused an increase in muscular and brain weight, the higher dosages of the opioid were detrimental, not only for muscle and brain, but also for both liver and spleen weight. A slight, although significant (P < 0.05), enhancement of serum dehydroepiandrosterone sulfate (DHEAS) level was found after the injection of 0.3 microgram/g desacetyl-alpha-MSH, whereas both the 0.3 and 3 micrograms/g doses of desacetyl-alpha-MSH and the 3 micrograms/g dose of alpha-MSH determined the rise of plasma androstenedione (P < 0.05). All tested melanocortins and opioids failed to modify the concentrations of corticosterone. Our results suggest that melanocortins and opioids can modulate early postnatal growth in rats either by direct or indirect mechanisms.     

Exploring the thiazole scaffold for the identification of new agents for the treatment of fluconazole resistant Candida

Cyclohexyliden- and 2-methylcyclohexyliden-hydrazo-4-arylthiazoles were synthesized and tested as antifungal agents. All compounds exhibited minimal inhibitory concentration (MIC) values comparable with those of fluconazole (FLC). Moreover, some compounds showed fungicidal activity at low concentration. Worth noting five out of nine compounds were active towards Candida albicans 25 FLC resistant isolated from clinical specimens. The cellular toxicity was evaluated and none of the compounds is toxic at the MIC. On the basis of our data we can conclude that these derivatives are promising agents for the treatment of resistant C. albicans.     

Molecular mechanisms of drug resistance and its reversal in cancer

Chemotherapy is the main strategy for the treatment of cancer. However, the main problem limiting the success of chemotherapy is the development of multidrug resistance. The resistance can be intrinsic or acquired. The resistance phenotype is associated with the tumor cells that gain a cross-resistance to a large range of drugs that are structurally and functionally different. Multidrug resistance arises via many unrelated mechanisms, such as overexpression of energy-dependent efflux proteins, decrease in uptake of the agents, increase or alteration in drug targets, modification of cell cycle checkpoints, inactivation of the agents, compartmentalization of the agents, inhibition of apoptosis and aberrant bioactive sphingolipid metabolism. Exact elucidation of resistance mechanisms and molecular and biochemical approaches to overcome multidrug resistance have been a major goal in cancer research. This review comprises the mechanisms guiding multidrug resistance in cancer chemotherapy and also touches on approaches for reversing the resistance.     

Antagonism betweenYersinia intermedia andYersinia enterocolitica in water

One strain of Yersinia enterocolitica and one strain of Y. intermedia were grown in peptone water at 25 or 37 degrees C, or in ground water at 15 degrees C. Similar growth rates were observed when these strains were cultivated separately in the same media and at the same temperature. Mixed cultures at 37 degrees C displayed equivalent growth rates. In contrast, mixed cultures incubated at 15 or 25 degrees C were regularly unfavourable to Y. enterocolitica, whereas they did not modify the growth of Y. intermedia. A bacteriophage active on Y. enterocolitica and not on Y. intermedia was characterized from the filtrate of mixed cultures at low temperatures. This phage produced by the lysogenic Y. intermedia strain might be a potential factor responsible for the inhibition of Y. enterocolitica, since no additional antibacterial factor or nutritional competition between Y. intermedia and Y. enterocolitica were found in the mixed cultures.     

Inhibition of mitochondrial protein synthesis influences the glucocorticoid sensitivity of lymphoid cells

Inhibition of mitochondrial protein synthesis impairs the formation of the 13 polypeptides encoded on the mitochondrial genome. These polypeptides are part of enzyme complexes involved in oxidative phosphorylation. Prolonged inhibition of mitochondrial protein synthesis thus reduces the oxidative phosphorylation capacity which ultimately results in impairment of energy-requiring processes. Via a different mechanism glucocorticoid hormones also decrease the oxidative phosphorylation capacity of, e.g., lymphoid cells. The present study shows that inhibition of mitochondrial protein synthesis influences glucocorticoid-induced responses of lymphoid cells in two opposing manners. (a) It is enhanced after induction in cells with a reduced oxidative phosphorylation capacity resulting from preceding inhibition of mitochondrial protein synthesis. This can be explained by the synergistic effects of glucocorticoids and prolonged inhibition of mitochondrial protein synthesis on energy-producing processes. (b) It is counteracted when mitochondrial protein synthesis is impaired during induction of the response. The latter observation suggests that mitochondrial protein synthesis is involved in the generation of glucocorticoid-induced effects on lymphoid cells.     

Existence of different forms of adrenocorticotropin in rat hypothalamus

Adrenocorticotropin (ACTH)-like immunoreactivity and bioactivity were extracted from rat hypothalamus and fractionated by high pressure liquid chromatography. Analysis of the fractions either by radioimmunoassay or bioassay (corticosteroid production from rat adrenal cells) revealed several peaks of immunoreactivity and bioactivity. Only 20-25% of total ACTH-like immunoreactivity and bioactivity eluted with the same retention time as authentic ACTH 1-39. The results suggest that different forms of ACTH exist in rat hypothalamus.     

Late Quaternary foraminiferal assemblages from western Ross Sea (Antarctica) in relation to the main glacial and marine lithofacies

Investigations on foraminifers from Upper Pleistocene–Holocene sediments were carried out on twelve cores from the western Ross Sea continental margin (Drygalski, Joides, North Victoria Land Basins) as part of a “Progetto Nazionale di Ricerche in Antartide” (P.N.R.A.) multidisciplinary project. Data on the foraminiferal frequency, species diversity, tests abundance and their state of preservation were presented as a synthesis of 404 core samples to establish their relationships with the main glacial and marine lithofacies of this area. A total of 126 benthic species, pertaining to 73 genera have been identified; just few taxa, such as Cibicides spp., Globocassidulina spp., Trifarina angulosa and Miliammina spp. being the most ubiquitous and in some cases the dominant species of these paleoenvironments. Two variants of Neogloboquadrina pachyderma, including thin and thick-shelled forms have been recovered. We propose to use these results to provide the degree of glacial control during the Last Glacial Maximum and the following Holocene retreat of the ice sheets. High test fragmentation, low diversity and density tests reflect higher glacial influence of the ice sheet in the Drygalski Basin, whereas the decreasing percentage of fragmentation and a relative increase of density and diversity in Drygalski, Joides and North Victoria Land Basins indicate the paleoenvironmental passage from the ice sheet to the ice shelf condition. The ice shelf retreat is well evidenced in the Joides Basin by a succession of levels barren of foraminifers alternating with high-density levels, rich in T. angulosa, followed by a total disappearance of the calcareous foraminifers. Open-marine settings indicative of lower glacial influence and increased corrosiveness of the water masses is testified by the Miliammina foraminiferal assemblage during the Holocene in Drygalski and Joides Basins cores. On the contrary, rich and abundant benthic and planktonic assemblages characterize the Holocene paleoenvironment of the North Victoria Land area, indicating that the water masses were less corrosive with respect to the other areas. In addition to the glacial reworking of the tests, and the dissolution due to the corrosive water mass conditions, the volcaniclastic sediments recovered in the North Victoria Land Basin cores also affected the condition of test preservation. In volcaniclastic sediments, older than about 20 ka BP, the foraminifers concentration tends to zero and, when present, their tests are highly damaged or completely broken.     

A mutant of the green alga Dunaliella salina constitutively accumulates zeaxanthin under all growth conditions

A novel mutant (zea1) of the halotolerant unicellular green alga Dunaliella salina is impaired in the zeaxanthin epoxidation reaction, thereby lacking a number of the beta-branch xanthophylls. HPLC analysis revealed that the zea1 mutant lacks neoxanthin (N), violaxanthin (V) and antheraxanthin (A) but constitutively accumulates zeaxanthin (Z). Under low-light physiological growth conditions, the zea1 (6 mg Z per g dry weight or 8 x 10(-16) mol Z/cell) had a substantially higher Z content than the wild type (0.2 mg Z per g dry weight or 0.5 x 10(-16) mol Z/cell). Lack of N, V, and A did not affect photosynthesis or growth of the zea1 strain. Biochemical analyses suggested that Z constitutively and quantitatively substitutes for N, V, and A in the zea1 strain. This mutant is discussed in terms of its commercial value and potential utilization by the algal biotechnology industry for the production of zeaxanthin, a high-value bioproduct.