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1.
Poly-trans-[(2-carboxyethyl)germasesquioxane] (Ge-132) is a water-soluble organogermanium compound that exerts various physiological effects, including anti-inflammatory activity and pain relief. In water, Ge-132 is hydrolyzed to 3-(trihydroxygermyl)propanoic acid (THGP), which in turn is capable of interacting with cis-diol compounds through its trihydroxy group, indicating that this compound could also interact with diol-containing nucleic acid constituents. In this study, we evaluated the ability of THGP to interact with nucleosides or nucleotides via nuclear magnetic resonance (NMR) analysis. In addition, we evaluated the effect of added THGP on the enzymatic activity of adenosine deaminase (ADA) when using adenosine or 2′-deoxyadenosine as a substrate. In solution, THGP indeed formed complexes with nucleotides or nucleosides through their cis-diol group. Moreover, the ability of THGP to form complexes with nucleotides was influenced by the number of phosphate groups present on the ribose moiety. Notably, THGP also inhibited the catalysis of adenosine by ADA in a concentration-dependent manner. Thus, interactions between THGP and important biological nucleic acid constituents might be implicated in the physiological effects of Ge-132.  相似文献   
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Administration of high doses of fluoride (F) can alter glucose homeostasis and lead to insulin resistance (IR). This study determined the profile of protein expression in the gastrocnemius muscle of rats with streptozotocin-induced diabetes that were chronically exposed to F. Male Wistar rats (60 days old) were randomly distributed into two groups of 18 animals. In one group, diabetes was induced through the administration of streptozotocin. Each group (D-diabetic and ND-non-diabetic) was further divided into 3 subgroups each of which was exposed to a different F concentration via drinking water (0 ppm, 10 ppm or 50 ppm F, as NaF). After 22 days of treatment, the gastrocnemius muscle was collected and submitted to proteomic analysis (2D-PAGE followed by LC-MS/MS). Protein functions were classified by the GO biological process (ClueGO v2.0.7+Clupedia v1.0.8) and protein-protein interaction networks were constructed (PSICQUIC, Cytoscape). Quantitative intensity analysis of the proteomic data revealed differential expression of 75 spots for ND0 vs. D0, 76 for ND10 vs.D10, 58 spots for ND50 vs. D50, 52 spots for D0 vs. D10 and 38 spots for D0 vs. D50. The GO annotations with the most significant terms in the comparisons of ND0 vs. D0, ND10 vs. D10, ND50 vs. D50, D0 vs. D10 and D0 vs. D50, were muscle contraction, carbohydrate catabolic processes, generation of precursor metabolites and energy, NAD metabolic processes and gluconeogenesis, respectively. Analysis of subnetworks revealed that, in all comparisons, proteins with fold changes interacted with GLUT4. GLUT4 interacting proteins, such as MDH and the stress proteins HSPB8 and GRP78, exhibited decreased expression when D animals were exposed to F. The presence of the two stress proteins indicates an increase in IR, which might worsen diabetes. Future studies should evaluate whether diabetic animals treated with F have increased IR, as well as which molecular mechanisms are involved.  相似文献   
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Abstract

This work evaluated the effects of commercial toothpastes and mouth rinses containing natural/herbal agents on biofilm viability, extracellular polysaccharide (EPS) production and on enamel demineralization in vitro. Microcosm biofilm was produced on bovine enamel for 5?days and treated daily with: Orgânico natural® (toothpaste/mouth rinse), Boni Natural Menta &; Malaleuca® (toothpaste/mouth rinse), Propolis &; Myrrh® (toothpaste), Colgate Total 12 Clean Mint® (toothpaste, positive control), Malvatricin® Plus (mouth rinse), PerioGard® (mouth rinse, positive control) or PBS (negative control). Tom’s Propolis &; Myrrh® and Colgate Total 12® toothpastes and Malvatricin® Plus and PerioGard® mouth rinses significantly reduced biofilm viability (p?® had significant effects on biofilm thickness and EPS. Despite the indication that Tom’s Propolis &; Myrrh® significantly reduced lesion depth, only Colgate Total 12® significantly reduced mineral loss. Malvatricin® Plus significantly reduced mineral loss and lesion depth, as did PerioGard®. Some herbal products, Malvatricin® Plus and Tom’s Propolis &; Myrrh®, showed anticaries effects.  相似文献   
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Biological Trace Element Research - The development of metallomics techniques has allowed for metallomics analysis of biological systems, enabling a better understanding of the response mechanisms...  相似文献   
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Biological Trace Element Research - The effect of duration of chronic treatment with fluoride (F, 50 mg/L as NaF) on the lipid profile, lipid droplets and triglycerides (TG) in liver was...  相似文献   
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The behavior of fluoride ions in biological systems has advantages and problems. On one hand, fluoride could be a mitogenic stimulus for osteoblasts. However, high concentrations of this element can cause apoptosis in rat and mouse osteoblasts. Toward an understanding of this effect, we examined the role of sodium fluoride (NaF) in two mouse calvaria osteoblasts during the mineralization process. The animals used were C3H/HeJ (C3) and C57BL/6J (B6) mice. The calvaria cells were cultured for 28 days in the presence of several doses of NaF (0, 5, 10, 25, 50, and 75 μM), and we performed the assays: mineralized nodule measurements, alkaline phosphatase (ALP) activity, determination of type I collagen, and matrix metalloproteinase-2 (MMP-2) activity. The results showed no effects on alkaline phosphatase activity but decreased mineralized nodule formation. In B6 cells, the NaF effect was already seen with 10 μM of NaF and a greater increase of cellular type I collagen, and MMP-2 activity was upregulated after 7 days of NaF exposure. C3 osteoblasts showed a reduction in the mineralization pattern only after 50 μM of NaF with a slight increase of type I collagen and downregulation of MMP-2 activity during the mineralization period. In conclusion, fluoride affects the production and degradation of the extracellular matrix during early onset and probably during the mineralization period. Additionally, the genetic factors may contribute to the variation in cell response to fluoride exposure, and the differences observed between the two strains could be explained by an alteration of the bone matrix metabolism (synthesis and degradation).  相似文献   
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BackgroundPulmonary sequelae (PS) in patients with chronic paracoccidioidomycosis (PCM) typically include pulmonary fibrosis and emphysema. Knowledge of the molecular pathways involved in PS of PCM is required for treatment and biomarker identification.Methodology/Principal findingsThis non-concurrent cohort study included 29 patients with pulmonary PCM that were followed before and after treatment. From this group, 17 patients evolved to mild/ moderate PS and 12 evolved severe PS. Sera from patients were evaluated before treatment and at clinical cure, serological cure, and apparent cure. A nanoACQUITY UPLC-Xevo QT MS system and PLGS software were used to identify serum differentially expressed proteins, data are available via ProteomeXchange with identifier PXD026906. Serum differentially expressed proteins were then categorized using Cytoscape software and the Reactome pathway database. Seventy-two differentially expressed serum proteins were identified in patients with severe PS compared with patients with mild/moderate PS. Most proteins altered in severe PS were involved in wound healing, inflammatory response, and oxygen transport pathways. Before treatment and at clinical cure, signaling proteins participating in wound healing, complement cascade, cholesterol transport and retinoid metabolism pathways were downregulated in patients with severe PS, whereas signaling proteins in gluconeogenesis and gas exchange pathways were upregulated. At serological cure, the pattern of protein expression reversed. At apparent cure pathways related with tissue repair (fibrosis) became downregulated, and pathway related oxygen transport became upregulated. Additionally, we identified 15 proteins as candidate biomarkers for severe PS.Conclusions/SignificanceDevelopment of severe PS is related to increased expression of proteins involved in glycolytic pathway and oxygen exchange), indicative of the greater cellular activity and replication associated with early dysregulation of wound healing and aberrant tissue repair. Our findings provide new targets to study mechanisms of PS in PCM, as well as potential biomarkers.  相似文献   
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Urine is an ideal source of materials to search for potential disease‐related biomarkers as it is produced by the affected tissues and can be easily obtained by noninvasive methods. 2‐DE‐based proteomic approach was used to better understand the molecular mechanisms of injury induced by fluoride (F?) and define potential biomarkers of dental fluorosis. Three groups of weanling male Wistar rats were treated with drinking water containing 0 (control), 5, or 50 ppm F? for 60 days (n = 15/group). During the experimental period, the animals were kept individually in metabolic cages, to analyze the water and food consumption, as well as fecal and urinary F? excretion. Urinary proteome profiles were examined using 2‐DE and Colloidal Coomassie Brilliant Blue staining. A dose‐response regarding F? intake and excretion was detected. Quantitative intensity analysis revealed 8, 11, and 8 significantly altered proteins between control vs. 5 ppm F?, control vs. 50 ppm F? and 5 ppm F? vs. 50 ppm F? groups, respectively. Two proteins regulated by androgens (androgen‐regulated 20‐KDa protein and α‐2μ‐globulin) and one related to detoxification (aflatoxin‐B1‐aldehyde‐reductase) were identified by MALDI‐TOF‐TOF MS/MS. Thus, proteomic analysis can help to better understand the mechanisms underlying F? toxicity, even in low doses. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 25:8–14 2011; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.20353  相似文献   
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