1,720,995 research outputs found
Administration of ciprofibrate to lactating mothers induces PPARα-signaling pathway in liver and kidney of suckling rats
- It is well known that the hypolipidemic drug ciprofibrate induces peroxisome proliferation in rodent liver, which in turn leads to the oxidative stress, and modifies some parameters related to cell proliferation and apoptosis. The administration of ciprofibrate to rats during the lactating period determined in their pups significant modifications in hepatic peroxisome enzyme activities, induction of the PPARalpha-target gene, Cyp4a10, and perturbation in cell proliferation and apoptosis, which affected the size of the liver. Moreover, this modification was associated to about two-fold induction of mRNA-PPARalpha. On the contrary, in the kidney, although a similar two-fold up-regulation of PPARalpha was detected, the induction of both peroxisomal enzyme activities and Cyp4a10 were weak, and no alterations were detected, neither in cell cycle nor in the size of the tissue. Our results indicate that the response to ciprofibrate is stronger in the liver than in the kidney of newborn rats
Altered vitamin B12 metabolism in the central nervous system is associated with the modification of ribosomal gene expression: new insights from comparative RNA dataset analysis
Recent studies have confirmed the direct role of vitamin B12 (VitB12) in the central nervous system (CNS) homeostasis; nevertheless, the detailed mechanisms are poorly understood. By analyzing RNA-Seq and microarray datasets obtained from databanks, this study aims to identify possible basic mechanisms, related to the brain, involved in altering the gene expression under VitB12 deficiency mimicking conditions. The database inquiry returned datasets generated from distinctly heterogeneous experimental sets and considering the quality and relevance requirements, two datasets from mouse and one from rat models were selected. The analyses of individual datasets highlighted a change in ribosomal gene expression in VitB12 deficiency mimicking conditions within each system. Specifically, a divergent regulation was observed depending on the animal model: mice showed a down regulation of the ribosomal gene expression, while rats an upregulation. Interestingly, E2f1 was significantly upregulated under VitB12 deficiency mimicking conditions in the animal models, with a greater upregulation in rats. The rat model also revealed putative E2F1 Transcription Factor Binding Sites (TFBSs) in the promoter of the differently regulated genes involved in ribosomal gene expression. This suggested the possibility that E2F1, being greater expressed in rats, could activate the ribosomal genes having E2F1 TFBSs, thus giving a plausible explication to the divergent regulation observed in animal models. Despite the great diversity of the experimental sets used to generate the datasets considered, a common alteration of the ribosomes exists, thereby indicating a possible basic and conserved response to VitB12 deficiency. Moreover, these findings could provide new insights on E2F1 and its association with CNS homeostasis and VitB12 deficiency. Graphical Abstract: [Figure not available: see fulltext.
Enhanced antibacterial and anti-quorum sensing activities of triclosan by complexation with modified β-cyclodextrins
Triclosan (TCS), an antimicrobial agent widely used in consumer and medical products, was complexed with 2-hydroxypropyl-β-cyclodextrin (HPβCD) and methyl-β-cyclodextrin (MβCD). Phase-solubility studies indicated that inclusion complexes of 1:1 stoichiometry were formed and allowed estimation of the associated equilibrium constants and free-energy changes. At the highest cyclodextrin concentrations investigated, an almost 20-fold increase in the apparent water solubility of TCS was determined. Susceptibility tests against Escherichia coli and Staphylococcus aureus showed that the TCS-HPβCD and TCS-MβCD complexes exhibited antibacterial properties higher than those of uncomplexed TCS. The two complexes were also found capable of interfering with cell-to-cell communication mechanisms in the C. violaceum model system relying on N-acylhomoserine lactone autoinducers. The inhibitory activity of TCS increased significantly upon inclusion of the drug in HPβCD or MβCD, with small differences between the two CDs. The results obtained suggest that the investigated complexes could be used for treating infections caused by TCS-susceptible pathogens or for preventing biofilm formation on indwelling medical devices such as catheters, stents and orthopedic implants. © 2013 Springer Science+Business Media Dordrecht
Differential modulation of PPARalpha and gamma target gene expression in the liver and kidney of rats treated with aspirin.
- Aspirin modified peroxisomal enzymatic activities both in the liver and renal cortex of rats, producing typical effects of peroxisomal proliferators (PPs). Although similar increments in beta-oxidation system and catalase activities were observed in both organs, induction of mRNA-Cyp4a10 and mRNA-FAT/CD36, target genes for peroxisome proliferator-activated receptors alpha (PPARalpha) and gamma (PPARgamma), respectively, was only present in the liver. There was no effect on liver mRNA-PPARalpha, while mRNA-PPARgamma was down-regulated, probably as a result of enzymatic inhibition of cyclooxygenases (COXs) by aspirin which has been shown to decrease the levels of PGJ2 and its metabolites, known as strong endogenous ligands for PPARgamma. Typical PP alterations in cell replication and apoptosis were not found during aspirin treatment or after withdrawal, suggesting that peroxisome proliferation occurs without inducing cell cycle alterations. Probably, the synergic action of both PPARalpha and PPARgamma receptors might reduce the impact on cell proliferation and apoptosis
La berberina – un alcaloide naturale con proprietà ipocolesterolemizzanti e antidiabetiche
Antimicrobial activity of methylglyoxal, a phytochemical found in some types of honey, against pathogenic bacteria
Recent evidence suggests that methylglyoxal (MG), a highly reactive
ketoaldehyde, is the main responsible for the unusually high antimicrobial
activity of some New Zealand honeys. To provide further support to this
hypothesis and assess the potential of MG as a new natural antimicrobial
agent, we performed comparative in-vitro activity tests on some of the
microorganisms most frequently associated with human infections,
including amethicillin-resistant Staphylococcus epidermidis (MRSE) strain
froma clinical isolate.Very similar activity profileswere observed by using
MG or amedical-grade (UMF 25+)Manuka honey as antimicrobial agents,
with the following susceptibility order: MRSE, S. aureus > E. coli, P.
mirabilis > P. aeruginosa. MG exhibited bacteriostatic and bactericidal
activity against all the microorganisms tested, with MIC and MBC values
ranging from1.05 to 4.22mMand 2.11 to 4.22mM, respectively.Experiments
made by adding 70mMMGto an artificial honey and an equimolar glucose
fructose mixture showed that the activity ofManuka honey arises primarily
fromthe presence of high levels ofMG.The remarkable antibacterial potency
of MG makes it an attractive candidate for the development of
pharmaceutical compositions for the treatment of microbial infections
Antibacterial and anti-quorum sensing activities of selected italian honeys against antibiotic-resistant pathogens
Three nectar honeys (eucalyptus, thyme and forest) and two honeydew honeys (fir and Metcalfa) from Italy were tested for their antibacterial activity against pathogens commonly associated with wound and burn infections, including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE) and vancomycin-resistant Enterococcus faecalis (VREF). All honeys showed bactericidal activity against the microorganisms used, with honeydew honeys being the most effective. They also inhibited, in a dose-dependent manner, violacein production in Chromobacterium violaceum, thus demonstrating their ability to affect quorum sensing-regulated biofilm formation. Overall, the results obtained suggest that the honeys examined may have potential for developing natural antimicrobial compositions or dressings for the treatment of infected wounds or burns
Neural Stem Cells and Nutrients: Poised Between Quiescence and Exhaustion
Adult neurogenesis initiated by neural stem cells (NSCs) contributes to brain homeostasis, damage repair, and cognition. Energy metabolism plays a pivotal role in neurogenic cell fate decisions regarding self-renewal, expansion and multilineage differentiation. NSCs need to fine-tune quiescence and proliferation/commitment to guarantee lifelong neurogenesis and avoid premature exhaustion. Accumulating evidence supports a model whereby calorie restriction or increased energy expenditure reinforce NSC quiescence and promote self-renewal. Conversely, growth/proliferation inputs and anabolic signals, although necessary for neurogenesis, deplete the NSCs pool in the long run. This framework incorporates the emerging neurogenic roles of nutrient-sensing signaling pathways, providing a rationale for the alarming connection between nutritional imbalances, metabolic disorders and accelerated brain aging
Methylglyoxal: A New Weapon against Staphylococcal Wound Infections?
Methylglyoxal (MG), a phytochemical present in some New Zealand honeys, was found to possess bactericidal activity against S. aureus and a methicillin-resistant strain of S. epidermidis. The MIC and MBC values were 1.05 and 2.11 mM, respectively. Inclusion of MG in a hydrogel resulted in an active and stable preparation suitable for treating wound or burn infections
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