Fasting reduces liver fibrosis in a mouse model for chronic cholangiopathies

Chronic cholangiopathies often lead to fibrosis, as a result of a perpetuated wound healing response, characterized by increased inflammation and excessive deposition of proteins of the extracellular matrix. Our previous studies have shown that food deprivation suppresses the immune response, which led us to postulate its beneficial effects on pathology in liver fibrosis driven by portal inflammation. We investigated the consequences of fasting on liver fibrosis in Abcb4^?/? mice that spontaneously develop it due to a lack of phospholipids in bile. The effect of up to 48 h of food deprivation was studied by gene expression profiling, (immuno)histochemistry, and biochemical assessments of biliary output, and hepatic and plasma lipid composition. In contrast to increased biliary output in the wild type counterparts, bile composition in Abcb4^?/? mice remained unchanged with fasting and did not influence the attenuation of fibrosis. Markers of inflammation, however, dramatically decreased in livers of Abcb4^?/? mice already after 12 h of fasting. Reduced presence of activated hepatic stellate cells and actively increased tissue remodeling further propelled a decrease in parenchymal fibrosis in fasting. This study is the first to show that food deprivation positively influences liver pathology in a fibrotic mouse model for chronic cholangiopathies, opening a door for new strategies to improve liver regeneration in chronic disease.     

Starvation induces phase-specific changes in the proteome of mouse small intestine

Food deprivation results in metabolic, structural, and functional changes in the small intestine that influences gut mucosal integrity, epithelial cell proliferation, mucin synthesis, and other processes. The underlying mechanisms are still unclear, which lead to the study of molecular effects of short-term and long-term starvation in the intestine of mice. A comparative proteomics approach, combining two-dimensional gel electrophoresis with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, was used to identify intestinal proteins whose expression is changed under different starvation conditions (0, 12, 24, and 72 h). In total, the expression levels of 80 protein spots changed significantly between the different groups. The results demonstrate that after 12 h of starvation, mainly proteins involved in glycolysis and energy metabolism show decreased expression levels. Starvation for 24 h results in a down-regulation of proteins involved in protein synthesis and amino acid metabolism. Simultaneously, proteins with a protective role, e.g., reg I and II, glutathione peroxidase 3, and carbonic anhydrase 3, are clearly up-regulated. The last starvation phase (72 h) is characterized by increased ezrin expression, which may enhance villus morphogenesis critical for survival. Together, these results provide novel insights in the intestinal starvation response and may contribute to improved nutritional support during conditions characterized by malnutrition.     

DIFFERENT TURNOVER RATES OF BRAIN RIBOSOMAL RIBONUCLEIC ACIDS IN MALE AND FEMALE RATS

Abstract— Following a single intracranial injection of [5-³H]orotic acid, the decay dynamics were determined for rRNAs of whole brain in male and female Wistar-inbred albino rats aged 2.5-3.5 months. The turnover rate for male brain rRNAs was significantly lower than in females (mean half-lives being, respectively, 12.2 ± 2.2 (S.D.M.) days, and 7.4 ± 1.3 days in four regression measurements). This difference was apparently not related to the turnover rate of acid-soluble brain nucleotides, which turned over much faster and at a similar rate in rats of both sexes; it also could not be connected with brain levels of rRNAs or DNAs, which were quite similar For males and females. The results are discussed in terms of possible sex hormone determination of brain RNA metabolic patterns especially in males.     

Dynamic Interaction of Hsp90 with Its Client Protein p53

Although the structure of the molecular chaperone Hsp90 has been extensively characterized by X-ray crystallography, the nature of the interactions between Hsp90 and its client proteins remains unclear. We present results from a series of spectroscopic studies that strongly suggest that these interactions are highly dynamic in solution. Extensive NMR assignments have been made for human Hsp90 through the use of specific isotopic labeling of one- and two-domain constructs. Sites of interaction of a client protein, the p53 DNA-binding domain, were then probed both by chemical shift mapping and by saturation transfer NMR spectroscopy. Specific spectroscopic changes were small and difficult to observe, but were reproducibly measured for residues over a wide area of the Hsp90 surface in the N-terminal, middle and C-terminal domains. A somewhat greater specificity, for the area close to the interface between the N-terminal and middle domains of Hsp90, was identified in saturation transfer experiments. These results are consistent with a highly dynamic and nonspecific interaction between Hsp90 and p53 DNA-binding domain in this chaperone-client system, which results in changes in the client protein structure that are detectable by spectroscopic and other methods.     

The adrenal cortex in female rats after estradiol or calcium treatment

Administration of estradiol or calcium, or combined, represents the classical therapeutic approach in the treatment of some menopausal symptoms. We have studied the effects of estradiol dipropionate (EDP) and calcium glucoheptonate (Ca) on morphological and hormonal features of the adrenal gland in 14-month-old female Wistar rats. The animals were treated with EDP (0.625 mg/kg b.w.) or Ca (11.4 mg/kg b.w.) daily for two weeks, with control rats receiving vehicle alone by the same schedule. The cell volumes in the zona glomerulosa (ZG) and zona fasciculata (ZF) were 11.2% and 5.5% greater (P<0.05) and in the zona reticularis (ZR) 13.0% smaller (P<0.05) in the EDP group than in the control group. In the Ca group, cell volume in the ZG was increased by 5.6% (P<0.05), while cell volumes in the ZF and ZR were decreased by 26.0% and 14.7%, respectively (P<0.05), in comparison with control values. Serum aldosterone and corticosterone concentrations were higher in the EDP-treated (by 27.8% and 19.8%, respectively) and Ca-treated (by 80.0% and 24.1%, respectively) groups in comparison with the control group (P<0.05). These data suggest that EDP and Ca treatments have stimulatory effects on the ZG and ZF, but inhibitory effects on the ZR in middle-aged female rats.     

Cancer incidence in a population living near a petrochemical facility and oil refinery

There is growing concern that pollution from petrochemical and oil refinery installations in Pancevo (Serbia) has increased the incidence of various diseases including cancer. The aim of our study was to investigate cancer incidence in Pancevo and to compare it with the region of central Serbia. Cancer incidence data were obtained from the corresponding Serbian Cancer Registries. Systematic local monitoring of benzene, toluene and methyl mercaptane in the atmosphere within Pancevo's industrial area indicated that the average monthly and yearly concentrations often exceeded permitted levels proposed by EU standards (5 microgm(-3)). Cancer incidence was lower in Pancevo than in central Serbia (the standardised incidence for all types of cancers in Pancevo was 218.3 and in central Serbia it was 241.7 per 100,000 inhabitants). The available data do not allow us to correlate air pollution in Pancevo with increased cancer incidence.     

Effect of Cytokinin and Auxin Treatments on Morphogenesis,Terpenoid Biosynthesis,Photosystem Structural Organization,and Endogenous Isoprenoid Cytokinin Profile in <Emphasis Type="Italic">Artemisia alba</Emphasis> Turra In Vitro

Developmental pattern modification in essential oil bearing Artemisia alba Turra was obtained by exogenous plant growth regulator (PGRs) treatments in vitro. Enhanced rooting (in PGR-free and auxin-treated plants) led to elevation of the monoterpenoid/sesquiterpenoid ratio in the essential oils of aerials. On the contrary, root inhibition and intensive callusogenesis [combined cytokinin (CK) and auxin treatments] reduced this ratio more than twice, significantly enhancing sesquiterpenoid production. Both morphogenic types displayed sesquiterpenoid domination in the underground tissues, which however differed qualitatively from the sesquiterpenoids of the aerials, excluding the hypothesis of their shoot-to-root translocation and implying the possible role of another signaling factor, affecting terpenoid biosynthesis. Inhibited rooting also resulted in a significant drop of endogenous isoprenoid CK bioactive-free bases and ribosides as well as CK N-glycoconjugates and in decreased trans-zeatin (transZ):cis-zeatin (cisZ) ratio in the aerials. Marked impairment of the structural organization of the photosynthetic apparatus and chloroplast architecture were also observed in samples with suppressed rooting. It is well known that in the plant cell monoterpenoid and transZ-type CKs biogenesis are spatially bound to plastids, while sesquiterpenoid and cisZ production are compartmented in the cytosol. In the present work, interplay between the biosynthesis of terpenoids and CK bioactive free bases and ribosides in A. alba in vitro via possible moderation of chloroplast structure has been hypothesized.     

Phenolic Profile of Artemisia alba Turra

The aim of this study was to evaluate flower and leaf methanol extracts of Artemisia alba Turra for their total phenolic and flavonoid contents, antioxidant capacity and to investigate their phenolic composition. The flower extract was richer in total phenolics and flavonoids and possessed higher antioxidant activity through DPPH and ABTS assays. The UHPLC‐PDA‐MS analysis of the flower and leaf methanol extracts revealed similar phenolic profile and allowed identification of 31 phenolic compounds (flavonoids, coumarins, and phenolic acids) by comparison with the respective reference compounds or tentatively characterized by their chromatographic behavior, UV patterns, and MS fragmentations. The presence of hispidulin, jaceosidin, desmethoxycentaureidin, and dicaffeoyl esters of quinic acid in A. alba is reported herein for the first time. The distribution of flavonoids in A. alba from different origins was discussed from chemotaxonomic point of view.