The Flavonol Quercitrin Hinders GSK3 Activity and Potentiates the Wnt/β-Catenin Signaling Pathway

The Wnt/β-catenin signaling pathway dictates cell proliferation and differentiation during embryonic development and tissue homeostasis. Its deregulation is associated with many pathological conditions, including neurodegenerative disease, frequently downregulated. The lack of efficient treatment for these diseases, including Alzheimer’s disease (AD), makes Wnt signaling an attractive target for therapies. Interestingly, novel Wnt signaling activating compounds are less frequently described than inhibitors, turning the quest for novel positive modulators even more appealing. In that sense, natural compounds are an outstanding source of potential drug leads. Here, we combine different experimental models, cell-based approaches, neuronal culture assays, and rodent behavior tests with Xenopus laevis phenotypic analysis to characterize quercitrin, a natural compound, as a novel Wnt signaling potentiator. We find that quercitrin potentiates the signaling in a concentration-dependent manner and increases the occurrence of the Xenopus secondary axis phenotype mediated by Xwnt8 injection. Using a GSK3 biosensor, we describe that quercitrin impairs GSK3 activity and increases phosphorylated GSK3β S9 levels. Treatment with XAV939, an inhibitor downstream of GSK3, impairs the quercitrin-mediated effect. Next, we show that quercitrin potentiates the Wnt3a-synaptogenic effect in hippocampal neurons in culture, which is blocked by XAV939. Quercitrin treatment also rescues the hippocampal synapse loss induced by intracerebroventricular injection of amyloid-β oligomers (AβO) in mice. Finally, quercitrin rescues AβO-mediated memory impairment, which is prevented by XAV939. Thus, our study uncovers a novel function for quercitrin as a Wnt/β-catenin signaling potentiator, describes its mechanism of action, and opens new avenues for AD treatments.     

Multifrequency backscattering tomography for constant and vertically varying backgrounds

To improve the resolution and image quality of the SFDT (Sigle-Frequency Diffraction Tomography), a special fast multi-frequency imaging method: Multi-Frequency Backscattering Tomography (MFBT) is introduced in this paper. The method uses only the backscattered waves (after plane wave decomposition) while maintaining the merit of multi-frequency method. The method is formulated for both the constant and vertically varying backgrounds. For the latter case the WKBJ approximation is used for the background Green's function. Formulas are derived both for volume scattering using the Born approximation and for boundary scattering using the physical optics approximation. Two reconstruction methods are presented. The backpropagation method can be used and has the same computation speed for both the constant and vertically varying backgrounds. Meanwhile the direct FT method is only formulated for the constant background, in which the backpropagation in z-direction is implemented by FFT and therefore the computation speed is significantly increased. Compared with the SFDT using backpropagation reconstruction, the MFBT is nearly N_z/log₂N_z faster, where N_z is the number of grid points in z-direction, and at the same time has a much better resolution and image quality. When N_z is big, the time saving is remarkable. Compared with other multi-frequency methods such as the multi-frequency holography (prestack migration), the speeding factor becomes N_fN_z/log₂N_z, where N_f, is the number of frequencies used. Numerical simulations for both constant and vertically varying backgrounds are performed to demonstrate the feasibility of the method and the quality of reconstructed images for different situations. Examples are also given to show that when the reconstruction procedure of constant background is applied to the case of vertically varying background, the image quality will be greatly deteriorated.©1994 John Wiley & Sons Inc     

Mineral migration from stainless steel, cast iron and soapstone (steatite) Brazilian pans to food preparations

Culinary utensils may release some inorganic elements during food preparation. Mineral migration can be beneficial for as long as it occurs in amounts adequate to the needs of the consumer or no toxicological implications are involved. In this study, the migrations of Fe, Mg, Mn, Cr, Ni and Ca, along seven cooking cycles were evaluated for two food preparations (polished rice and commercial tomato sauce, the latter as an acid food), performed in unused stainless steel, cast iron and soapstone pans, taking refractory glass as a blank. Minerals were determined by inductively coupled plasma optical emission spectrometry (ICP OES). The utensils studied exhibited different rates, patterns and variability of migration depending on the type of food. Regression analysis of the data revealed that, as a function of the number of cycles, the iron pans released increasing amounts of iron when tomato sauce was cooked (y = 70.76x + 276.75; R2 = 0.77). The soapstone pans released calcium (35 and 26 mg/kg), magnesium (25 and 15 mg/kg) into the tomato sauce and rice preparations, respectively. Additionally, the commercial tomato sauce drew manganese (3.9 and 0.6 mg/kg) and some undesirable nickel (1.0 mg/kg) from the soapstone material, whereas the stainless steel pans released nickel at a lower rate than steatite and in a diminishing fashion with the number o cooking cycles, while still transferring some iron and chromium to the food. We conclude that while cast iron and glass could be best for the consumer's nutritional health, stainless steel and steatite can be used with relatively low risk, provided acid foods are not routinely prepared in those materials.     

Leukemia-Induced Cellular Senescence and Stemness Alterations in Mesenchymal Stem Cells Are Reversible upon Withdrawal of B-Cell Acute Lymphoblastic Leukemia Cells

Leukemic cell growth in the bone marrow (BM) induces a very stressful condition. Mesenchymal stem cells (MSC), a key component of this BM niche, are affected in several ways with unfavorable consequences on hematopoietic stem cells favoring leukemic cells. These alterations in MSC during B-cell acute lymphoblastic leukemia (B-ALL) have not been fully studied. In this work, we have compared the modifications that occur in an in vitro leukemic niche (LN) with those observed in MSC isolated from B-ALL patients. MSC in this LN niche showed features of a senescence process, i.e., altered morphology, increased senescence-associated β-Galactosidase (SA-βGAL) activity, and upregulation of p53 and p21 (without p16 expression), cell-cycle arrest, reduced clonogenicity, and some moderated changes in stemness properties. Importantly, almost all of these features were found in MSC isolated from B-ALL patients. These alterations rendered B-ALL cells susceptible to the chemotherapeutic agent dexamethasone. The senescent process seems to be transient since when leukemic cells are removed, normal MSC morphology is re-established, SA-βGAL expression is diminished, and MSC are capable of re-entering cell cycle. In addition, few cells showed low γH2AX phosphorylation that was reduced to basal levels upon cultivation. The reversibility of the senescent process in MSC must impinge important biological and clinical significance depending on cell interactions in the bone marrow at different stages of disease progression in B-ALL.     

Screening of microorganisms for bioconversion of (−)β-pinene and R-(+)-limonene to α-terpineol

This work is focused on the bioconversion of (−)β-pinene and R-(+)-limonene to α-terpineol. To carry out the present study, 400 microorganisms were tested for their ability to bioconvert the substrates. From the microorganisms, no one was able to convert R-(+)-limonene and 4 were able to bioconvert (−)-β-pinene to oxygenated monoterpenes. The metabolites recovered were α-terpineol (2856.54 ± 50.23 mg/L) and fenchol (traces) for Aspergillus niger ATCC 16404, α-terpineol (688.13 ± 41.27 mg/L) for A. niger ATCC 9642, α-terpineol (172.07 ± 32.94 mg/L) for A. niger ATCC 1004 and α-terpineol (24.38 ± 2.78 mg/L) and trans-pinocarveol (traces) for Penicillium camembertii ATCC 4845. After screening and optimization experiments, the best experimental condition for bioconversion of (−)β-pinene to α-terpineol was established using A. niger ATCC 16404 at 35 °C without addition of vitamin solution, yielding a conversion in α-terpineol of 15494.34 ± 193.87 mg/L.