MicroRNA 148a Suppresses Tuberculous Fibrosis by Targeting NOX4 and POLDIP2

Extracellular matrix production by pleural mesothelial cells in response to Mycobacterium tuberculosis contributes to tuberculous fibrosis. NOX4 is involved in the pathogenesis of tuberculous fibrosis. In this study, we evaluated whether NOX4 gene-targeting microRNAs showed protective effects in tuberculosis fibrosis. TargetScan prediction software was used to identify candidate microRNAs that bind the 3′ UTRs of NOX4, and microRNA-148a (miR-148a) was selected as the best miRNA candidate. A repressed and forced expression assay in Met5A cells was performed to investigate the causal relationship between miR-148a and NOX4. The role of miR-148a in tuberculous pleural fibrosis was studied using a murine model of Mycobacterium bovis bacillus Calmette–Guérin (BCG) pleural infection. Heat-killed M. tuberculosis (HKMT) induces NOX4 and POLDIP2 expression. We demonstrated the inhibitory effect of miR-148a on NOX4 and POLDIP2 expression. The increased expression of miR-148a suppressed HKMT-induced collagen-1A synthesis in PMC cells. In the BCG pleurisy model, miR-148a significantly reduced fibrogenesis and epithelial mesenchymal transition. High levels of miR-148a in tuberculous pleural effusion can be interpreted as a self-limiting homeostatic response. Our data indicate that miR-148a may protect against tuberculous pleural fibrosis by regulating NOX4 and POLDIP2.     

ApoA1 Deficiency Reshapes the Phenotypic and Molecular Characteristics of Bone Marrow Adipocytes in Mice

In the present study, we studied the effect of apolipoprotein A-1 (APOA1) on the spatial and molecular characteristics of bone marrow adipocytes, using well-characterized ApoA1 knockout mice. APOA1 is a central regulator of high-density lipoprotein cholesterol (HDL-C) metabolism, and thus HDL; our recent work showed that deficiency of APOA1 increases bone marrow adiposity in mice. We found that ApoA1 deficient mice have greatly elevated adipocytes within their bone marrow compared to wild type counterparts. Morphologically, the increased adipocytes were similar to white adipocytes, and displayed proximal tibial-end localization. Marrow adipocytes from wild type mice were significantly fewer and did not display a bone-end distribution pattern. The mRNA levels of the brown/beige adipocyte-specific markers Ucp1, Dio2, Pat2, and Pgc1a; and the expression of leptin were greatly reduced in the ApoA1 knock-out in comparison to the wild-type mice. In the knock-out mice, adiponectin was remarkably elevated. In keeping with the close ties of hematopoietic stem cells and marrow adipocytes, using flow cytometry we found that the elevated adiposity in the ApoA1 knockout mice is associated with a significant reduction in the compartments of hematopoietic stem cells and common myeloid, but not of the common lymphoid, progenitors. Moreover, the ‘beiging’-related marker osteopontin and the angiogenic factor VEGF were also reduced in the ApoA1 knock-out mice, further supporting the notion that APOA1—and most probably HDL-C—regulate bone marrow microenvironment, favoring beige/brown adipocyte characteristics.     

A novel chelate-assisted C−C bond formation on a Cd(II) complex of an asymmetric heptadentate(N7) tripodal Schiff base ligand

Cadmium(II) complexes of some potentially heptadentate tripodal Schiff base ligands with the general formula N{(CH₂)_nNCHC₅H₄N}₂{(CH₂)_mNCHC₅H₄N}) (where n = m = 2, L₂₂₂; n = 2, m = 3, L₃₂₂; n = 3, m = 2, L₃₃₂) have been studied. These ligands are products of the full condensation of a number of tripodal tetraamines with 2-pyridinecarboxaldehyde. An unusual reaction of an additional 2-pyridine-carboxaldehyde with a methylene group adjacent to the imine bond only during template preparation of [Cd(L₃₃₂)]²⁺ was observed. The latter reaction is a novel chelate-assisted C?C bond formation because it is occurred only where a rigid five-membered chelate ring is present.     

Films from oat spelt arabinoxylan plasticized with glycerol and sorbitol

The development of packaging films based on renewable materials is an important and active area of research today. This is the first extensive study focusing on film‐forming properties of an agrobiomass byproduct, namely, oat spelt arabinoxylan. A plasticizer was needed for cohesive film formation, and glycerol and sorbitol were compared. The tensile properties of the films varied with the type and amount of the polyol. With a 10% (w/w) plasticizer content, the films containing glycerol had higher tensile strength than the films containing sorbitol, but with a 40% plasticizer content, the result was the opposite. Sorbitol‐plasticized films retained their tensile properties better than films with glycerol during 5 months of storage. The films were semicrystalline with similar crystallinity indices of 0.20–0.26. The largest crystallites (9.5 nm) were observed in the film with 40% glycerol. The softening of films with 40% (w/w) glycerol started at a significantly lower relative humidity (RH) than that of the corresponding sorbitol‐containing films. The films with sorbitol also had lower water vapor permeability (WVP) than the films with glycerol. The films plasticized with 10% (w/w) sorbitol had a WVP value of 1.1 g mm/(m²·d·kPa) at the RH gradient of 0/54%. The oxygen permeability of films containing 10% (w/w) glycerol or sorbitol was similar: 3 cm³·μm/(m²·d·kPa) at 50–75% RH. A higher plasticizer content resulted in more permeable films. Permeation of sunflower oil through the films was not detected. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

A neural network approach to predict activity coefficients

Artificial neural networks (ANNs) and a group‐contribution approach were used to develop an algorithm to predict activity coefficients for binary solutions. The Levenberg–Marquardt algorithm was used to train the ANN and to predict the parameters of the Margules equation. The ANN was trained using phase‐equilibrium database from DECHEMA. The selected systems include alcohols, phenols, aldehydes, ketones, and ethers. The trim mean based on 20% data elimination was selected as the best representation of the Margules‐equation parameters. The algorithm was validated with 121 VLE systems and results show that the ANN provides a relative improvement over the UNIFAC method.     

Oriented polycrystalline mesoporous CeO2 with enhanced pore integrity

Mesoporous CeO₂ particles are synthesized using a sol–gel method involving Pluronic P123 or F127 tri-block copolymer and cerium acetate hydrate. Transmission electron microscopy reveals well defined meso-channels of about 10 nm in diameter and a wall framework consisting of highly oriented polycrystalline CeO₂. The [0 0 1] axis of the crystals is found to be aligned parallel to the meso-channels, and lattice coherency of [1 0 0] or [0 1 0] also exists in perpendicular plane to the channel. A cooperative self-assembly of the tri-block copolymer and Ce⁴⁺ species is believed to occur, along with the precipitation of nano-crystalline CeO₂ in the sol–gel process. It is proposed that the preferential orientation may result from a favored linkage of the low-order Miller indices {0 0 1} planes of CeO₂ to the PEO segment in the PEO–PPO–PEO tri-block copolymer micelles. The unique structural characteristics of meso-CeO₂ appear to contribute to maintaining the pore integrity during the synthesis as well as in a post-fabrication in situ TEM heating test.     

Legumin allergens from peanuts and soybeans: effects of denaturation and aggregation on allergenicity

Legumin proteins Ara h 3 from peanuts and glycinin from soybeans are increasingly described as important allergens. The stability of an allergen's IgE binding capacity towards heating and digestion is considered an important characteristic for food allergens. We investigated the effects of heating and digestion on the IgE binding of Ara h 3 and glycinin. Both proteins are relatively stable to denaturation, having denaturation temperatures ranging from 70 to 92 degrees C, depending on their quaternary structure and the ionic strength. Aggregates were formed upon heating, which were partly soluble for glycinin. Heating slightly decreased the pepsin digestion rate of both allergens. However, heating did not affect the IgE binding capacity of the hydrolyzates, as after only 10 min of hydrolysis no IgE binding could be detected any more in all samples. Peanut allergen Ara h 1, when digested under equal conditions, still showed IgE binding after 2 h of hydrolysis. Our results indicate that the IgE binding capacity of legumin allergens from peanuts and soybeans does not withstand peptic digestion. Consequently, these allergens are likely unable to sensitize via the gastro-intestinal tract and cause systemic food allergy symptoms. These proteins might thus be less important allergens than was previously assumed.