p62/SQSTM1 indirectly mediates remote multipotent mesenchymal cells and rescues bone loss and bone marrow integrity in ovariectomized rats

Intramuscular administration of p62/SQSTM1 (sequestosome1)-encoding plasmid demonstrated an anticancer effect in rodent models and dogs as well as a high safety profile and the first evidence of clinical benefits in humans. Also, an anti-inflammatory effect of the plasmid was reported in several rodent disease models. Yet, the mechanisms of action for the p62 plasmid remain unknown. Here, we tested a hypothesis that the p62-plasmid can act through the modulation of bone marrow multipotent mesenchymal cells (MSCs). We demonstrated that a p62 plasmid can affect MSCs indirectly by stimulating p62-transfected cells to secrete an active ingredient(s) sensed by untransfected MSCs. When we transfected MSCs with the p62-plasmid, collected their supernatant, and added it to an untransfected MSCs culture, it switched the differentiation state and prompt osteogenic responses of the untransfected MSCs. According to an accepted viewpoint, ovariectomy leads to bone pathology via dysregulation of MSCs, and restoring the MSC homeostasis would restore ovariectomy-induced bone damage. To validate our in vitro observations in a clinically relevant in vivo model, we administered the p62 plasmid to ovariectomized rats. It partially reversed bone loss and notably reduced adipogenesis with concurrent reestablishing of the MSC subpopulation pool within the bone marrow. Overall, our study suggests that remote modulation of progenitor MSCs via administering a p62-encoding plasmid may constitute a mechanism for its previously reported effects and presents a feasible disease-preventing and/or therapeutic strategy.     

Structures of some carotenoids from the pulp of Persea americana

The identity of chrysanthemaxanthin as a major pigment in avocado pulp has been confirmed by MS and the identity of neoxanthin similarly established. A carbonyl pigment was identified as 3-hydroxy-sintaxanthin. Two new UV fluorescent apocarotenoids were isolated. On the basis of spectrum, behaviour in acid and MS, one of these is assigned the structure 5,8-epoxy-5,8-dihydro- 10′-apo-β-caroten-3, 10′-diol. The other has an acid labile pentaene chromophore, and structure (1) has been tentatively assigned on similar evidence. These are the first natural allyic apocarotenols whose structures have been established.     

Evolutionary physiology by data of publications for 1965–2005

Evolutionary physiology as independent direction of physiology was formed in the XX century and was rapidly developing in its second half. To evaluate some tendencies of this process, we analyzed publications in Journal of Evolutionary Biochemistry and Physiology, one of the leading specialized periodicals on this problem. Analysis of works published for 4 decades has shown that the majority of papers deals with study of evolution of function of the nervous system (40–60 papers per year), less papers concern study of functions of sensory and visceral systems (20–30 per year). Among the used method, the most widely spread is the comparative-physiological method. By the end of the 1990s the number of works with use of methods of embryophysiology decreased. In the performed studies, predominant are physiological methods. Use of biochemical methods decreased, while of methods of molecular biology increased. The most often used objects of studies were mammals. By the end of the XX—beginning of the XXI century, in the greater number of papers the object of study has become human, while the number of publications in which experiments were performed on amphibians, reptiles, and birds decreased. More than a half of all works were carried out in St. Petersburg (Leningrad); the number of papers submitted from Moscow institutions gradually decreased, but the number of works from regions of Russia rose. Most studies were performed at institutes of the Russian Academy of Sciences and universities, while the number of papers from institutes of the Russian Academy of Medical Sciences decreased. For the last few years, several generalizations on evolution of functions and functional evolution have been formulated; handbooks and monographs on problems of evolutional physiology have been published.     

Carotenoids in pulp,peel and leaves of Persea americana

A complex pattern of chloroplast pigments was found to be common to pulp, peel and leaves of avocado. This is explained by the presence of chlorophyll in the ripe fruit and its peel. Two chromoplast-specific pigments were found in ripe pulp and are tentatively identified as α-citraurin and mimulaxanthin. The identity of the latter and of neochrome, was established inter alia by the MS. The xanthophylls occur esterified to a major extent in pulp but entirely free in peel. The coexistence of chloroplast and chromoplast pigments in avocado fruit make this a suitable object for the ultrastructural studies of the origin of the chromoplasts.     

Optical‐mechanical signatures of cancer cells based on fluctuation profiles measured by interferometry

We propose to establish a cancer biomarker based on the unique optical‐mechanical signatures of cancer cells measured in a noncontact, label‐free manner by optical interferometry. Using wide‐field interferometric phase microscopy (IPM), implemented by a portable, off‐axis, common‐path and low‐coherence interferometric module, we quantitatively measured the time‐dependent, nanometer‐scale optical thickness fluctuation maps of live cells in vitro. We found that cancer cells fluctuate significantly more than healthy cells, and that metastatic cancer cells fluctuate significantly more than primary cancer cells. Atomic force microscopy (AFM) measurements validated the results. Our study shows the potential of IPM as a simple clinical tool for aiding in diagnosis and monitoring of cancer. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Nerve Growth Factor Mediates Monosialoganglioside-Induced Release of Fibronectin and J1/Tenascin from C6 Glioma Cells

C6 rat glioma cells incubated in serum-free medium with D-[14C]glucosamine secrete, on stimulation with nerve growth factor (NGF) or monosialogangliosides (MSGs), several glycoproteins (Gps), the most prominent of which are a 270-, 220-, and 69-kDa Gp. Several growth factors, hormones, phorbol ester, and disialo- and trisialogangliosides did not stimulate secretion. Western blot analysis of the conditioned medium from C6 cells stimulated with NGF or MSG identified one distinct band of approximately 220 kDa for fibronectin and J1/tenascin, which comigrated. Antiserum to NGF prevented NGF-stimulated release and also blocked MSG-evoked release. The 220-kDa band was labeled after pulse labeling with [35S]methionine in the presence of NGF, and by a 15-min chase period radioactively labeled J1/tenascin could be immunoprecipitated. Tunicamycin drastically inhibited almost completely release of the 220-kDa Gp labeled by D-[14C]glucosamine or [35S]methionine. These results extend the range of neurotrophic properties attributed to NGF to cells of glial origin and suggest that NGF regulates secretion of extracellular matrix proteins. MSG stimulation of fibronectin and J1/tenascin secretion may be mediated by NGF or an NGF-like molecule also secreted by the C6 glioma cells.